Digestive System Diseases Commons^™

Chronic Pancreatitis, Pain, And Anxiety In An Alcohol And High Fat Mouse Model, Tiffanie Clinkinbeard

Theses and Dissertations--Gerontology

Homeodynamic space (HDS) shrinks as vulnerability increases with aging and repeated damage to the cells. HDS is lost in alcoholic pancreatitis patients due to overconsumption of alcohol, smoking, and high fat diets. Etiologically relevant animal models for study of chronic pancreatitis (CP) are needed. In order to begin filling this gap a central purpose of this dissertation research was to examine relationships between the alcohol and high fat diet (AHF) and pancreatitis with attention to hypersensitivity and anxiety-like behaviors. The AHF diet induced pancreatitis described here etiologically mimics human risk factors of AHF consumption for advancement to alcoholic CP.

In …

Restoring Digestive Health, Kristin M. Corbin, Dnp, Aprn, Fnp-C

Doctor of Nursing Practice (DNP) Translational and Clinical Research Projects

Purpose: The purpose of this translational research project was to outline the healthcare problems associated with Functional Gastrointestinal Disorders and to explore the effectiveness of a gastrointestinal protocol utilized at Atlanta Center for Holistic and Integrative Medicine. The goal of this protocol is to restore digestive health with probiotics, digestive enzymes, and glutamine.

Background: Functional Gastrointestinal Disorders affect one in every four adults in the United States. These disorders encompass a variety of symptoms including diarrhea, constipation, cramping, abdominal pain, flatulence, reflux, and bloating without an identified physiological cause. There is currently no cure for Functional Gastrointestinal Disorders and treatment …

Nash: Non-Alcoholic Steatohepatitis, Jennifer Heck

Nursing Student Class Projects (Formerly MSN)

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease which refers to the presence of hepatic steatosis without significant intake of alcohol. Non-alcoholic fatty liver disease develops in a variety of forms from reversible simple steatosis to non-alcoholic steatohepatitis (NASH), which if left unchecked can progress to liver fibrosis, cirrhosis and even develop into hepatocellular carcinoma (Mells et al., 2014). NAFLD is thought to be nonthreatening, but with progression over several years could lead to NASH. A strong link between obesity and NASH has been shown. In addition to obesity, insulin resistance (type II diabetes mellitus), and hyperlipidemia all …

Rhabdomyolysis – Understanding The Mechanics, Tawnya Tucker

Nursing Student Class Projects (Formerly MSN)

As a hospital healthcare provider on a Medical/Surgical Unit the probability of examining and treating a patient diagnosed with rhabdomyolysis is scarce. Knowing the mechanics of the disease will assist the provider in evaluating and treating the patient. Awareness of the pathophysiology of the disease is vital in accurately diagnosing and treating the disease. The role of the advanced practice nurse is fundamental in distinguishing possible causes of the phenomenon by recognizing signs and symptoms that occur with the disease. Completing a thorough physical exam on the patient and obtaining special lab tests will assist in identifying the ailment. Treating …

Acute Pancreatitis, Laura Skidmore

Nursing Student Class Projects (Formerly MSN)

Acute pancreatitis (AP) can be a singular incidence, a relapsing process or exacerbations of chronic pancreatitis. AP is a rapidly developing inflammatory disorder of the pancreas and can affect other organ systems. The process begins when pancreatic enzymes are activated prematurely and leak into surrounding tissue. The digestive process begins before reaching the intestines. AP is characterized clinically by abdominal pain and elevated levels of pancreatic enzymes in the blood. The pathogenesis is not fully understood however, a number of conditions are known to induce the disorder such as gallstones and chronic alcohol abuse (Schub & Kornusky, 2014)

Site-Specific Immunomodulator: A Novel Treatment For Crohn's Disease, Brian Bressler, Kevin P. Bethel, Ralf Kleef, Sophie L. Reynolds, Simon Sutcliffe, David W. Mullins, Hal Gunn

Dartmouth Scholarship

We investigated the mechanism of action, safety, and efficacy of the Site-Specific Immunomodulator (SSI) QBECO, a novel immunotherapy for Crohn’s disease (CD). Using human monocytic THP-1 cells, we demonstrate that SSI QBECO (derived from the common colon bacteria E. coli) activates macrophages to an M1 phenotype (associated with enhanced capacity to eliminate bacteria and activate innate immune responses). We assessed SSI QBECO in a compassionate use protocol of ten adult patients with active CD. Patients with moderate to severe clinical symptoms receiving conventional CD treatments and/or complementary therapies were included, except patients receiving anti-TNF medications. SSI QBECO was self-administered subcutaneously …

Effects Of Brain-Derived Neurotrophic Factor And Its Signaling Pathway On Sensory Neuronal Activation During Colitis, Fiza Hashmi

Theses and Dissertations

Visceral hypersensitivity is the heightened response to sensory stimuli. Visceral sensations are transmitted through primary afferent neurons in the dorsal root ganglion (DRG) and the sensitization of the neural pathway leads to modification in spinal ascending and descending neurons. The aim of this investigation is to determine the effects of brain-derived neurotrophic factor (BDNF) and its signaling pathway on sensory neuronal activation during colitis. In order to evaluate this, levels of calcitonin-gene related peptide (CGRP), a neuropeptide marker for nociceptive transmission, and phosphorylated cAMP-response element binding protein (pCREB), a molecular switch in neuronal plasticity, were studied in response to BDNF …

Does Your Child Have Reflux Or Could There Be More To It Than That, Cody Elam

Nursing Student Class Projects (Formerly MSN)

Eosinophilic esophagitis (EE) is differentiated from Gastroesophageal Reflux Disease (GERD) by endoscopic and histopathologic examination. The hallmark of EE is eosinophilic infiltration of the esophagus. EE has been defined as “a clinicopathologic entity, combining clinical data on (1) relevant symptoms (distinct in the pediatric or adult populations with mostly food impaction and dysphagia in adults and feeding intolerance, failure to thrive, and GERD symptoms in children); (2) esophageal biopsies with adequate histologic findings in the esophageal biopsies (>15 eosinophils/high power field [HPF]); and (3) exclusion of other diseases with overlapping features, especially GERD” (Genevay, Rubbia-Brandt, & Rougemont, 2010, p.816). …

Licorice Consumption Causing Hypokalemia And Lethal Dysrhythmias, Gina Grosscup

Nursing Student Class Projects (Formerly MSN)

This report describes a case in which approximately a two-month exposure of licorice root tea consumption containing glycyrrhizic acid (GA) produced generalized weakness, secondary hypertension, hyporeflexia and hypokalemia, leading to a reentry dysrhythmia of ventricular fibrillation. Although licorice root has been used for medicinal purposes dating back centuries the potential toxic side effects can be life threatening without early recognition. Most licorice candies in the western world contain artificial flavoring but the use of actual licorice root containing GA is common in many Middle-Eastern, Far Eastern and European countries. The purpose of this report is two-fold, first to describe the …

The Role Of Amp-Activated Protein Kinase (Ampk) In Regulating The Early Stages Of Acute Pancreatitis, Mohamed Shitia

Honors Scholar Theses

Acute pancreatitis is an inflammatory disease that is initiated by the activation and retention of digestive zymogens inside pancreatic acinar cells (acini). It is proposed that adenosine monophosphate-activated protein kinase (AMPK) regulates early responses of acute pancreatitis in acini. A recent study shows that induction of experimental pancreatitis in isolated rat acini with supraphysiologic cerulein (orthologue of cholecystokinin) increases intracellular zymogen activation, but decreases AMPK levels. Furthermore, in vitro pharmacologic stimulation of AMPK reduces zymogen activation, having a protective effect. In this study, the effectiveness of two AMPK activators was examined in two separate in vivo pancreatitis models. In the …

Lrh1 As A Driving Factor For Cancer Development, Alissa M. Margraf

Senior Honors Projects

LRH1 as a driving factor for cancer development

Alissa Margraf, Qi Tang, Qiushi Lin, Xiaoqun Dong

Department of Biomedical and Pharmaceutical Science, College of Pharmacy, The University of Rhode Island, Pharmacy Building, 7 Greenhouse Road, Kingston, RI 02881 USA

Cancer is a major public health problem worldwide. Colon cancer ranks as the third most common causes of cancer mortality in the United States, with an estimated 96,830 new cases and 50,310 deaths in 2014. Colon cancer develops in the digestive tract where benign growths called polyps transform into malignant tumors. Colon cancer cells invade and destroy nearby tissue and can …

Eculizumab In The Successful Treatment Of Postpartum Hemolytic Uremic Syndrome - A Case Report, Craig A. Mackaness Do, Frederick S. Fleszler Md

Department of Medicine

No abstract provided.

Microbiota, Oral Microbiome, And Pancreatic Cancer, Dominique S. Michaud, Jacques Izard

Department of Food Science and Technology: Faculty Publications

Only 30% of patients diagnosed with pancreatic cancer survive one year post-diagnosis. Progress in understanding the causes of pancreatic cancer has been made, including solidifying the associations with obesity and diabetes, and a proportion of cases should be preventable through lifestyle modifications. Unfortunately, identifying reliable biomarkers of early pancreatic cancer has been extremely challenging, and no effective screening modality is currently available for this devastating form of cancer. Recent data suggest the microbiota may play a role in the disease process, but many questions remain. Future studies focusing on the human microbiome, both etiologically and as a marker of disease …

Celiac Disease As A Model For The Evolution Of Multifactorial Disease In Humans, Aaron Sams, John Hawks

Human Biology Open Access Pre-Prints

Celiac disease (CD) is a multifactorial chronic inflammatory condition that results in injury of the mucosal lining of the small intestine upon ingestion of wheat gluten and related proteins from barley and rye. Although the exact mechanisms leading to CD are not fully understood, the genetic basis of CD has been relatively well characterized. In this review we briefly review the history of discovery, clinical presentation, pathophysiology, and current understanding of the genetics underlying CD risk. Then, we discuss what is known about the current distribution and evolutionary history of genes underlying CD risk in light of other evolutionary models …

Attenuation Of Parenteral Nutritionassociated Liver Disease By Omega-3 Long-Chain Polyunsaturated Fatty Acids, Emma Monique Tillman

Theses and Dissertations (ETD)

No abstract provided.

Macromolecular Complexes Of Cystic Fibrosis Transmembrane Conductance Regulator Alter Fluid Transport In Inflammatory Bowel Disorders, Kavisha Arora

Theses and Dissertations (ETD)

Macromolecular complexes of cystic fibrosis transmembrane conductance regulator (CFTR) comprise of network of proteins that can regulate cAMP-/cGMP-activated CFTR chloride channel function. We report the physical and functional coupling of CFTR with nitric oxide (NO) producing enzyme-inducible nitric oxide synthase (iNOS) at the apical plasma membrane in inflammatory bowel disease (IBD). The complex formation requires the scaffolding protein Na+ /H+ exchanger regulatory factor 2 (NHERF2). We demonstrate that iNOS is overexpressed at or near the apical plasma membrane of gut epithelial cells in IBD and, through the stimulation of the NO-cGMP pathway, generates compartmentalized cGMP underneath the plasma membrane. This …

Icad Deficiency In Human Colon Cancer And Predisposition To Colon Tumorigenesis: Linkage To Apoptosis Resistance And Genomic Instability, Youssef Errami, Hassan Brim, Karine Oumouna-Benachour, Mustapha Oumouna, Amarjit S. Naura, Hogyoung Kim, Jihang Ju, Christian J. Davis, Jong G. Kim, Hassan Ashktorab, Kenneth Fallon, Ming Xu, Jianhua Zhang, Luis Del Valle, A Hamid Boulares

School of Medicine Faculty Publications

We previously showed that DNA fragmentation factor, which comprises a caspase-3-activated DNase (CAD) and its inhibitor (ICAD), may influence the rate of cell death by generating PARP-1-activating DNA breaks. Here we tested the hypothesis that ICAD-deficient colon epithelial cells exhibiting resistance to death stimuli may accumulate additional genetic modifications, leading to a tumorigenic phenotype. We show that ICAD deficiency may be associated with colon malignancy in humans. Indeed, an examination of ICAD expression using immunohistochemistry in an array of both colon cancer and normal tissues revealed that ICAD expression levels were severely compromised in the cancerous tissues. Upon DNA damage …

In Adults With Acute Diarrhea, Which Treatment Is More Effective Between Loperamide And Racecadotril?, Lorena A. Castillo

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine which treatment is more effective between loperamide and racecadotril to treat acute diarrhea in adults.

STUDY DESIGN: Review of three English language primary randomized controlled studies published from 1999-2005.

DATA SOURCES: First study was a RCT that was double blinded, double placebo, parallel study group and second and third study was RCT single blinded, comparative parallel group that all compared efficacy of loperamide and racecadotril. These were all found by using PubMed, COCHRANE and NCBI.

OUTCOMES MEASURED: Each of the studies measured the efficacy of each …

Mast Cell Activation And Clinical Outcome In Pediatric Cholelithiasis And Biliary Dyskinesia., Craig A. Friesen, Nancy Neilan, James F. Daniel, Kim Radford, Jennifer Verrill Schurman, Ding-You Li, Linda Andre, Shawn D. St Peter, G W. Holcomb Iii

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The current study was undertaken to determine the degree of activation of gallbladder mucosal mast cells, whether mast cell (MC) density or activation differ between patients with and without a positive clinical response to cholecystectomy, and whether either density or activation correlate with gallbladder emptying.

RESULTS: Fifteen biliary dyskinesia (BD) and 13 symptomatic cholelithiasis (CL) patients undergoing cholecystectomy were prospectively enrolled. Gallbladder wall MC density (by immunohistochemistry) and activation (by electron microscopy) were determined. Clinical response was evaluated 30 days post-cholecystectomy on a 5-point Likert-type scale. A complete or nearly complete clinical response was seen in 100% of CL …

Application Of Prodrugs To Inflammatory Diseases Of The Gut, Helieh S. Oz, Jeffrey L. Ebersole

Center for Oral Health Research Faculty Publications

Oral delivery is the most common and preferred route of drug administration although the digestive tract exhibits several obstacles to drug delivery including motility and intraluminal pH profiles. The gut milieu represents the largest mucosal surface exposed to microorganisms with 10^10-12 colony forming bacteria/g of colonic content. Approximately, one third of fecal dry matter is made of bacteria/ bacterial components. Indeed, the normal gut microbiota is responsible for healthy digestion of dietary fibers (polysaccharides) and fermentation of short chain fatty acids such as acetate and butyrate that provide carbon sources (fuel) for these bacteria. Inflammatory bowel disease (IBD) results …

Requirements For Vibrio Cholerae Hapr Binding And Transcriptional Repression At The Hapr Promoter Are Distinct From Those At The Apha Promoter, Wei Lin, Gabriela Kovacikova, Karen Skorupski

Dartmouth Scholarship

Virulence gene expression in certain strains of Vibrio cholerae is regulated in response to cell density by a quorum-sensing cascade that influences the levels of the LuxR homolog HapR through small regulatory RNAs that control the stability of its message. At high cell density, HapR represses the expression of the gene encoding the virulence gene activator AphA by binding to a site between −85 and −58 in the aphA promoter. We show here that a second binding site for HapR lies within the hapR promoter from which it functions to repress its own transcription. This site, as determined by gel …

Identification Of A Tcpc-Tcpq Outer Membrane Complex Involved In The Biogenesis Of The Toxin-Coregulated Pilus Of Vibrio Cholerae, Niranjan Bose, Ronald K. Taylor

Dartmouth Scholarship

The toxin-coregulated pilus (TCP) of Vibrio cholerae and the soluble TcpF protein that is secreted via the TCP biogenesis apparatus are essential for intestinal colonization. The TCP biogenesis apparatus is composed of at least nine proteins but is largely uncharacterized. TcpC is an outer membrane lipoprotein required for TCP biogenesis that is a member of the secretin protein superfamily. In the present study, analysis of TcpC in a series of strains deficient in each of the TCP biogenesis proteins revealed that TcpC was absent specifically in a tcpQ mutant. TcpQ is a predicted periplasmic protein required for TCP biogenesis. Fractionation …

Mechanism Of Toxt-Dependent Transcriptional Activation At The Vibrio Cholerae Tcpa Promoter, Robin R. Hulbert, Ronald K. Taylor

Dartmouth Scholarship

The AraC homolog ToxT coordinately regulates virulence gene expression in Vibrio cholerae. ToxT is required for transcriptional activation of the genes encoding cholera toxin and the toxin coregulated pilus, among others. In this work we focused on the interaction of ToxT with the tcpA promoter and investigated the mechanism of ToxT-dependent transcriptional activation at tcpA. Deletion analysis showed that a region from −95 to +2 was sufficient for ToxT binding and activation, both of which were simultaneously lost when the deletion was extended to −63. A collection of point mutations generated by error-prone PCR revealed two small regions required …

Vibrio Cholerae H-Ns Silences Virulence Gene Expression At Multiple Steps In The Toxr Regulatory Cascade, Melinda B. Nye, James D. Pfau, Karen Skorupski, Ronald K. Taylor

Dartmouth Scholarship

H-NS is an abundant nucleoid-associated protein involved in the maintenance of chromosomal architecture in bacteria. H-NS also has a role in silencing the expression of a variety of environmentally regulated genes during growth under nonpermissive conditions. In this study we demonstrate a role for H-NS in the negative modulation of expression of several genes within the ToxR virulence regulon ofVibrio cholerae. Deletion of hns resulted in high, nearly constitutive levels of expression of the genes encoding cholera toxin, toxin-coregulated pilus, and the ToxT virulence gene regulatory protein. For the cholera toxin- and ToxT-encoding genes, elevated expression in an …