Research

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Cytoskeletal Changes Induced by Allosteric Modulators of Calcium Sensing Receptor in Esophageal Epithelial Cells

 


 

An Extremely Rare Type of Gastric Carcinoma in a Male Teenager

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Eosinophilic Esophagitis Research – published in Clinical Immunology: Alterations in junctional proteins, inflammatory mediators and extracellular matrix molecules in eosinophilic esophagitis

Solange M. Abdulnour-Nakhoul, Youhanna Al-Tawil, Alex A. Gyftopoulos, Karen L. Brown, Molly Hansen, Kathy F. Butcher, Alexandra P. Eidelwein, Robert A. Noel, Edd Rabon, Allison Posta, Nazih L. Nakhoul, Alterations in junctional proteins, inflammatory mediators and extracellular matrix molecules in eosinophilic esophagitisClinical Immunology, Volume 148, Issue 2, August 2013, Pages 265-278

Abstract

Eosinophilic esophagitis (EoE), an inflammatory atopic disease of the esophagus, causes massive eosinophil infiltration, basal cell hyperplasia, and sub-epithelial fibrosis. To elucidate cellular and molecular factors involved in esophageal tissue damage and remodeling, we examined pinch biopsies from EoE and normal pediatric patients. An inflammation gene array confirmed that eotaxin-3, its receptor CCR3 and interleukins IL-13 and IL-5 were upregulated. An extracellular matrix (ECM) gene array revealed upregulation of CD44 & CD54, and of ECM proteases (ADAMTS1 & MMP14). A cytokine antibody array showed a marked decrease in IL-1a and IL-1 receptor antagonist and an increase in eotaxin-2 and epidermal growth factor. Western analysis indicated reduced expression of intercellular junction proteins, E-cadherin and claudin-1 and increased expression of occludin and vimentin. We have identified a number of novel genes and proteins whose expression is altered in EoE. These findings provide new insights into the molecular mechanisms of the disease.

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Eosinophilic Esophagitis: Morphological and Functional Alterations

Purpose of the Study

The purpose of this study is to learn more about how the esophageal epithelium (the lining of the food tube) acts and changes in children diagnosed with Eosinophilic Esophagitis compared to children without this disease. Eosinophilic Esophagitis (EoE) is a condition that causes inflammation (aggravation, redness, swelling) and damage to the esophagus. This study involves collecting a tissue sample (biopsy) from the esophagus in persons with or without the disease. These samples will be studied by scientists to learn how the tissue reacts to acid and other injuries. The major benefit from this study is to increase knowledge about the lining of the esophagus and how it changes in a person who has EoE. Another goal of the study is to find new ways to help people with EoE.

A total of 180 participants are needed for this study (90 children with EoE, 90 children without EoE). Only those patients who need a biopsy for medical reasons will have the research biopsy taken. Therefore, if the doctor determines during the procedure that a medically indicated biopsy is not necessary, the research biopsy will not be taken.

Who Can Participate?

Eligibility

  1. Child is between ages of 2-20 inclusive, male or female
  2. Patient requires a medically indicated upper endoscopy

Patient cannot participate if:

  1. Child has esophageal varices
  2. Child is in general poor health condition (e.g. has an infections disease(s) such as AIDS, hepatitis, etc.)
  3. Those who require only a “therapeutic endoscopy” (such as esophageal dilatation or extraction of a foreign body, or capsule placement ) and who do NOT therefore need a biopsy taken for medical reasons
  4. Day of procedure or in previous 2 weeks: Taking anti-coagulants
  5. Day of procedure or in previous 3 days: Taking non-steroidal anti-inflammatory drugs (NSAIDS) (e.g. aspirin – Bayer, ibuprophen – Motrin, Advil)

Study Activities

  1. Requires a one time biopsy, completion of demographic form, and data collection (height/weight, vital signs, medical history, current medications, dietary history, and allergies).
  2. Participation also includes the time period that is needed for the researchers at Tulane University to study the biopsies (3 years) and time for publication of results. It is not anticipated that we will need to contact you during this time, so participation is essentially only the day of the procedure.

Cost & Compensation for Participation

There are no extra costs for participating in this research study, as you/your child will not be charged for biopsies taken for research purposes. Also, there will be no payment to you or your child for participation in this study.

 

Abstract Accepted

Preliminary data from our Eosinophilic Esophagitis research study has been accepted as an abstract poster presentation. The abstract, Gene Expression Profile of Inflammatory Mediators and Extracellular Matrix and Adhesion Molecules in Eosinophilic Esophagitis (781818,) will be presented during Digestive Disease Week, to be held at the Ernest N. Morial Convention Center in New Orleans, LA, May 1 – May 5, 2010. A copy of the abstract is below:

ABSTRACT BODY:

Introduction:
Eosinophilic esophagitis (EoE) is a disease of the esophagus of increasing prevalence, encountered in children and adults. It is an inflammation of the esophagus, presumed to be of allergic origin, causing linear furrows and thin crepe-like mucosa. EoE does not respond to acid suppression therapy and can lead to dysphagia and esophageal strictures. Microscopic observation reveals massive eosinophil infiltration, remodeling of the esophageal epithelium, severe basal cells hyperplasia and subepithelial fibrosis. Our aim is to investigate the cellular and molecular factors involved in esophageal tissue damage and remodeling.

Methods:
We used real-time qPCR to study the expression of two panels of genes in pinch biopsies obtained during routine endoscopy procedures in EoE and normal pediatric patients (NL). The first panel contains 84 genes involved in the inflammatory response. The second panel contains 84 genes playing a role in extracellular matrix (ECM) structure, cell-to-cell communications and cell-matrix adhesion. We also used cytokines and growth factors protein arrays as well as immunohistochemistry (IHC) to determine and localize specific proteins involved in the above pathways.

Results:
The inflammation gene array data show that eotaxin 3 and its receptor CCR3 are very prominently upregulated (~200 folds) and (~23 folds) respectively. Interleukins (IL), IL13 and IL5 are upregulated by ~10 and ~4 folds respectively. These data are consistent with previously reported observations. In the ECM gene panel, CD44 and CD54 (ICAM1), both hyaluronan binding molecules, and genes for ECM proteases (ADAMTS1 and MMP14) are upregulated significantly. Collagen genes (COL6A1 and COL15A1) are upregulated (~3 folds), whereas COL14A1 is downregulated (~2 folds). IHC experiments using an antibody to CD44 showed more intense staining in EoE biopsies than in NL. A label-based cytokine and growth factors antibody array showed an increase in epidermal growth factor (EGF) and fibroblast growth factor (FGF7) in EoE biopsies.

Conclusion:
We have identified a number of novel genes whose expression is altered in EoE. Further investigating their role in inflammation and esophageal tissue damage could reveal the mechanisms of remodeling observed in the disease.

Authors:
Abdulnour-Nakhoul, Solange M.; Al-Tawil, Youhanna S.; Eidelwein, Alexandra P.; Noel, R. Adam; Hansen, Molly; Gyftopoulos, Alex A.; Butcher, Kathy F.; Brown, Karen L.; Nakhoul, Nazih.

An Inflammatory Bowel Disease Multicenter, Prospective, Long-term Registry of Pediatric Patients (DEVELOP)

GI for Kids, PLLC is participating in a multicenter, prospective, long-term, observational registry of pediatric patients with a confirmed diagnosis of Inflammatory Bowel Disease, which includes Crohn’s disease, Ulcerative Colities and Indeterminate Colitis (CD, UC, and IC). The patient observation period is planned for approximately 20 years; and the registry includes 50-100 sites in the United States and Europe.

The purpose of this study is to obtain long-term safety information on the patient’s disease and medications for IBD. Results will be used to assist physicians in improving patient care with regard to clinical outcomes, and patient quality of life.

Close to 5,000 participants from the US and Europe (Belgium, Denmark, France, Germany, Italy, The Netherlands, Canada and England) have been enrolled in the DEVELOP Registry study.  Currently 85% live in the United States and 15% live in the EU.  Enrollment goal is 6,000 participants.

Many patients are entering their 8th year in the study. DEVELOP plans to continue the registry until all patients have completed 20 years of participation.  A transition plan has been established to enable the Registry to continue to follow patients who are no longer being seen by the Pediatric Gastroenterologist.

Our clinic currently has 41 patients participating in this importa

Nitazoxanide to Treat Exacerbations of Pediatric Inflammatory Bowel Disease (IBD)

Our practice had this abstract accepted for presentation at the 2008 North American Society for Pediatric Gastroenterology Hepatology and Nutrition (NASPGHAN-CDHNF) Clinical and Scientific Symposium in San Diego, CA. This study involved a retrospective chart review of patients treated with Nitazoxanide who had exacerbations of IBD. We found that Nitazoxanide was well tolerated and appears to be effective for the treatment of IBD exacerbations in pediatric patients. Further studies are warranted to confirm this observation.


 

 

 

Nitazoxanide Case Study Poster