Digestive System Diseases Commons^™

Reduced Gut Microbiome Protects From Alcohol-Induced Neuroinflammation And Alters Intestinal And Brain Inflammasome Expression, Patrick P. Lowe, Benedek Gyongyosi, Abhishek Satishchandran, Arvin Iracheta-Vellve, Yeonhee Cho, Aditya Ambade, Gyongyi Szabo

Open Access Articles

BACKGROUND: The end-organ effects of alcohol span throughout the entire body, from the gastrointestinal tract to the central nervous system (CNS). In the intestine, alcohol use changes the microbiome composition and increases gut permeability allowing translocation of microbial components into the circulation. Gut-derived pathogen-associated signals initiate inflammatory responses in the liver and possibly elsewhere in the body. Because previous studies showed that the gut microbiome contributes to alcohol-induced liver disease, we hypothesized that antibiotic administration to reduce the gut microbiome would attenuate alcohol-induced inflammation in the brain and small intestine (SI).

METHODS: Six- to 8-week-old C57BL/6J female mice were ...

Fxr And Tgr5 Agonists Ameliorate Liver Injury, Steatosis, And Inflammation After Binge Or Prolonged Alcohol Feeding In Mice, Arvin Iracheta-Vellve, Charles D. Calenda, Jan Petrasek, Aditya Ambade, Karen Kodys, Luciano Adorini, Gyongyi Szabo

Open Access Articles

Bile acids (BAs) activate various dedicated receptors, including the farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5). The FXR agonist obeticholic acid (OCA) is licensed for the treatment of primary biliary cholangitis and has shown promising results in NASH patients, whereas TGR5 agonists target inflammation and metabolism. We hypothesized that FXR and/or TGR5 agonists may be therapeutic in early alcoholic liver disease (ALD) in mice, in which hepatic inflammation plays a major role. OCA, INT-777, and INT-767 are BA derivatives with selective agonist properties for FXR, TGR5, or both, respectively. These compounds were tested in ...

Microrna-96 Promotes Schistosomiasis Hepatic Fibrosis In Mice By Suppressing Smad7, Xufeng Luo, Dongmei Zhang, Jun Xie, Qin Su, Xing He, Ruipu Bai, Guangping Gao, Weiqing Pan

UMass Center for Clinical and Translational Science Supported Publications

Infection with Schistosoma causes aberrant expression of host microRNAs (miRNAs), and normalizing the levels of dysregulated miRNAs can attenuate pathology. Here, we show that the host miRNA, miR-96, is markedly upregulated during the progression of hepatic schistosomiasis. We demonstrate that elevation of miR-96 induces hepatic fibrosis in infected mice by suppressing the expression of its target gene, Smad7. We show that infection with Schistosoma induces the expression of transforming growth factor beta1 (TGF-beta1), which in turn upregulates the expression of miR-96 through SMAD2/3-DROSHA-mediated post-transcriptional regulation. Furthermore, inhibition of miR-96 with recombinant adeno-associated virus 8 (rAAV8)-mediated delivery of Tough ...

Vancomycin Delays Clindamycin-Induced Fatality In The Hamster Model Of Clostridioides [Clostridium] Difficile Infection, Amelia E. Fox-King, Chrisabelle Mefferd, Jacqueline R. Phan, Nancy O. Nou, Ernesto Abel-Santos, Brian P. Hedlund

LSAMP Poster Presentations

Antibiotics can leave the host gut microbiome susceptible to Clostridioides [Clostridium] difficile colonization and lethal toxin production. For instance, clindamycin-induced susceptibility to C. difficile infection (CDI) results in rapid fatality in hamster models, yet vancomycin has been shown to offer increased survival in hamsters challenged with C. difficile. We aim to develop an antibiotic treatment that will facilitate CDI susceptibility without prompt fatality in hamster models. An antibiotic regimen starting with a continuous vancomycin treatment along with a single clindamycin dosage is thought to reduce the major disruption in the indigenous gut microbiome and prevent clindamycin-induced death. Quantitative polymerase chain ...

Hepatocarcinoma With Tumor Thrombus Occupying The Right Atrium And Portal Vein In A Patient With Hereditary Hemochromatosis And Liver Cirrhosis, Olga Hilda Orasan, Andreea Maria Stefan, Laura Urian, Anca Mihailov, Ovidiu Fabian, Flaviu Muresan, Iulia Breaban, Sorina Cezara Secara, Simina Tarmure Sarlea, Vasile Negrean, Dorel Sampelean, Angela Cozma

Journal of Mind and Medical Sciences

We present the case of a 46-year old patient with Child-Pugh class C cirrhosis with MEDL-Score 16, and hepatocellular carcinoma invading the inferior vena cava and the right atrium. The etiology of cirrhosis is type 1 hereditary hemochromatosis with positive HFE C282Y/C282Y and H63D/H63D mutations. A systematic review of the literature was performed and only 30 cases of hepatocellular carcinoma with tumor thrombosis extending into the right atrium have been described. To our knowledge, this is the first case that evidences the presence in hereditary hemochromatosis of hepatocellular carcinoma with atypical invasion into the right atrium. Screening of ...

Reduced Incidence And Better Liver Disease Outcomes Among Chronic Hcv Infected Patients Who Consume Cannabis, Adeyinka Adejumo, Oluwole Muyiwa Adegbala, Kelechi Lauretta Adejumo, Terence N. Bukong

Open Access Articles

Background and Aim: The effect of cannabis use on chronic liver disease (CLD) from Hepatitis C Virus (HCV) infection, the most common cause of CLD, has been controversial. Here, we investigated the impact of cannabis use on the prevalence of CLD among HCV infected individuals.

Methods: We analyzed hospital discharge records of adults (age > /= 18 years) with a positive HCV diagnosis. We evaluated records from 2007 to 2014 of the Nationwide Inpatient Sample (NIS). We excluded records with other causes of chronic liver diseases (alcohol, hemochromatosis, NAFLD, PBC, HBV, etc.). Of the 188,333 records, we matched cannabis users to ...

Intestinal P-Glycoprotein Exports Endocannabinoids To Prevent Inflammation And Maintain Homeostasis, Rose L. Szabady, Christopher Louissaint, Anneke Lubben, Bailu Xie, Shaun Reeksting, Christine Tuohy, Zachary Demma, Sage Foley, Christina S. Faherty, Alejandro Llanos-Chea, Andrew J. Olive, Randall J. Mrsny, Beth A. Mccormick

Open Access Articles

Neutrophil influx into the intestinal lumen is a critical response to infectious agents, but is also associated with severe intestinal damage observed in idiopathic inflammatory bowel disease. The chemoattractant hepoxilin A3, an eicosanoid secreted from intestinal epithelial cells by the apically restricted efflux pump multidrug resistance protein 2 (MRP2), mediates this neutrophil influx. Information about a possible counterbalance pathway that could signal the lack of or resolution of an apical inflammatory signal, however, has yet to be described. We now report a system with such hallmarks. Specifically, we identify endocannabinoids as the first known endogenous substrates of the apically restricted ...

Heat Stroke As A Cause Of Liver Failure And Evaluation Of Liver Transplant, Paulo N.A. Martins, Isabel M. A. Bruggenwirth, James Mcdaid, Martin Hertl, Tatsuo Kawai, Nahel Elias, Raymond T. Chung, James F. Markmann

Open Access Articles

Heat stroke is a multiple organ dysfunction syndrome of poorly understood pathogenesis. Exertional heat stroke with acute liver failure is a rarely reported condition. Liver transplant has been recommended as treatment in cases of severe liver dysfunction; however, there are only 5 described cases of long-term survival after this procedure in patients with heat stroke. Here, we present 2 cases of young athletes who developed heat stroke. Both patients developed acute liver failure and were listed for liver transplant. Liver function tests of one patient improved, and he was discharged on postoperative day 13. The other patient showed no signs ...

Single-Center Experience With Liver Transplant Using Donors With Very High Transaminase Levels, Paulo N.A. Martins, Amanda Rawson, Babak Movahedi, Isabel M. A. Bruggenwirth, Natasha H. Dolgin, Ann-Britt Martins, Paria Mahboub, Adel Bozorgzadeh

Open Access Articles

OBJECTIVES: Elevation of transaminases has been used as a marker of hepatic ischemic injury and as a crucial parameter for liver graft assessment. However, analysis of serum transaminases has limitations regarding the quantitative assessment of liver necrosis and is not a reliable predictor of outcomes.

MATERIALS AND METHODS: We retrospectively reviewed the medical records of all liver transplants (N = 238) performed at the UMass Memorial Medical Center from 2009 to 2013.

RESULTS: Fourteen liver grafts showed high peak aminotransferases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) at > 1000 U/L. This high aminotransferase group was compared with 224 donors with ...

Video Capsule Endoscopy As A Tool For Evaluation Of Obscure Overt Gastrointestinal Bleeding In The Intensive Care Unit, Shahrad Hakimian, Salmaan Jawaid, Yurima Guilarte-Walker, Jomol Mathew, David R. Cave

Open Access Articles

Background and study aims: Video capsule endoscopy (VCE) is a minimally invasive tool that helps visualize the gastrointestinal tract from the esophagus to the right colon without the need for sedation or preparation. VCE is safe with very few contraindications. However, its role and safety profile in the intensive care unit (ICU) population have not been reported. The aim of this study is to evaluate the safety, efficacy, and feasibility of VCE use in ICU patients. Patients and methods: We conducted a single-center retrospective observational study of patients who underwent VCE for evaluation of obscure overt gastrointestinal bleeding in the ...

Comparing Efficacy Of Lumen-Apposing Stents To Plastic Stents In The Endoscopic Management Of Mature Peripancreatic Fluid Collections: A Single-Center Experience, Matthew J. Fasullo, Yasir Al-Azzawai, Joan Kheder, Jeffrey Abergel, Wahid Y. Wassef

Open Access Articles

Introduction: Mature peripancreatic fluid collection (MPFC) is a known and often challenging consequence of acute pancreatitis and often requires intervention. The most common method accepted is the "step-up approach," which consists of percutaneous drainage followed, if necessary, by minimally invasive retroperitoneal necrosectomy. Our paper aims to distinguish between plastic stents and lumen-apposing stents in the endoscopic management of MPFC in terms of morbidity, mortality, and haste of fluid collection resolution.

Methods: A retrospective analysis was performed at UMass Memorial Medical Center in patients with a diagnosis of MPFC. Utilizing medical records, clinical data, radiology, as well as endoscopic evidence, patients ...

Unique Surgical Approach To A Twisted Ileal-Anal Pouch, Hannah Buettner, Maria X. Kiely, Mengdi Yao, James Yoo, Lilian Chen

Open Access Articles

Total proctocolectomy with ileal pouch-anal anastomosis can restore gastrointestinal continuity in patients requiring colectomy for ulcerative colitis, however, it can be associated with high morbidity. Reoperation for pouch-related complications is technically challenging and often leads to deterioration of pouch function or need for permanent stoma. We report a case of acute on chronic small bowel obstruction secondary to a 360-degree twist in the small bowel introduced during creation of the ileal-anal pouch. Our novel approach at repair has not been reported in past literature which included resection and re-anastomosis of the small bowel proximal to the pouch allowing for pouch ...

Alcohol Consumption Promotes Colorectal Carcinoma Metastasis Via A Ccl5-Induced And Ampk-Pathway-Mediated Activation Of Autophagy, Haodong Zhao, Danlei Chen, Rui Cao, Shiqing Wang, Dandan Yu, Yakun Liu, Yu Jiang, Mei Xu, Jia Luo, Siying Wang

Pharmacology and Nutritional Sciences Faculty Publications

There is a definite relationship between alcohol consumption and colorectal cancer (CRC) development. We investigated effect of alcohol consumption on CRC patients’ progression and prognosis by utilizing epidemiological data and found patients with alcohol consumption increased risks of tumor-node-metastasis (TNM), organ metastasis and poorer prognosis. Because their tumor tissues displayed increased expression of C-C chemokine ligand 5 (CCL5), we hypothesized CCL5 might participate in cancer progression in such patients. Ethanol increased the secretion of CCL5 in two CRC cell lines, HT29 and DLD-1. Treatment with CCL5 directly increased migratory ability of these cells, whereas neutralization or knockdown of CCL5 can ...

Radical Social Ecology As Deep Pragmatism: A Call To The Abolition Of Systemic Dissonance And The Minimization Of Entropic Chaos, Arielle Brender

Student Theses 2015-Present

This paper aims to shed light on the dissonance caused by the superimposition of Dominant Human Systems on Natural Systems. I highlight the synthetic nature of Dominant Human Systems as egoic and linguistic phenomenon manufactured by a mere portion of the human population, which renders them inherently oppressive unto peoples and landscapes whose wisdom were barred from the design process. In pursuing a radical pragmatic approach to mending the simultaneous oppression and destruction of the human being and the earth, I highlight the necessity of minimizing entropic chaos caused by excess energy expenditure, an essential feature of systems that aim ...

In Vivo And In Vitro Studies Of Cry5b And Nicotinic Acetylcholine Receptor Agonist Anthelmintics Reveal A Powerful And Unique Combination Therapy Against Intestinal Nematode Parasites, Yan Hu, Melanie Miller, Bo Zhang, Thanh-Thanh Nguyen, Martin K. Nielsen, Raffi V. Aroian

Open Access Articles

BACKGROUND: The soil-transmitted nematodes (STNs) or helminths (hookworms, whipworms, large roundworms) infect the intestines of ~1.5 billion of the poorest peoples and are leading causes of morbidity worldwide. Only one class of anthelmintic or anti-nematode drugs, the benzimidazoles, is currently used in mass drug administrations, which is a dangerous situation. New anti-nematode drugs are urgently needed. Bacillus thuringiensis crystal protein Cry5B is a powerful, promising new candidate. Drug combinations, when properly made, are ideal for treating infectious diseases. Although there are some clinical trials using drug combinations against STNs, little quantitative and systemic work has been performed to define ...

A Case Of Synchronous Colorectal Carcinoma Manifested As Three Separate Colon Masses, Alyssa Imperatore Do, Linda Szczurek Do, Facos, Alan Shienbaum Do

Stratford Campus Research Day

Colorectal cancer is the second leading cause of cancer-related deaths in the United States amongst cancers that affect both genders. Synchronous colorectal cancer is greater than one primary lesion detected on initial presentation and occurs about 5% of the time.

This is a 78 year-old female with past medical history of left-sided breast cancer treated with neoadjuvant chemotherapy who presented with symptomatic anemia found to have a hemoglobin of five and positive fecal occult blood test. Patient was transfused and taken for EGD/colonoscopy, which showed three polypoid rectal lesions and three separate colon masses. Preliminary pathology showed high grade ...

Gist- An Unusual Case Of Gi Bleeding, Lucy Joo Do, Justin Derosa Do, Drew Chiesa Do, Darshan Roy Md

Stratford Campus Research Day

This is a unique case of a female who was diagnosed and treated with a GIST (gastrointestinal stromal cell tumor) of the stomach.The purpose is to deliver awareness and education to clinicians of this rare malignancy by emphasizing its presentation and characteristics.

A Case Of Signet Ring Cell Colon Carcinoma Initially Presenting As Acute Diverticulitis, Justin Derosa Do, Jonathan Foster Do, Drew Chiesa Do, Darshan Roy Md

Stratford Campus Research Day

This is a unique case of a female with an acute bout of diverticulitis who six weeks later on follow up colonoscopy, was found to have signet ring cell colon carcinoma. The purpose is to deliver awareness of this rare type of colon malignancy, emphasize the continued need for screening colonoscopy, and to provide the reader with a distinct and thought provoking spin on the conventional diagnosis of diverticulitis.

Myeloid Sarcoma: A Rare Cause Of Small Bowel Obstruction, Jonathan Sedeyn Do, Phd, Karlbuto Alexandre, Alan J. Sheinbaum Do, Adeshola Fakulujo Md, Facs

Stratford Campus Research Day

Myeloid sarcoma is a rare and aggressive tumor of myelogenous origin that uncommonly presents in the small bowel. Here we describe the case of a 29 year old male with a two week history of worsening abdominal pain associated with nausea and bilious vomiting. The patient displayed tenderness in the epigastric and periumbilical region with grossly normal lab values. On CT he was found to have a small bowel obstruction with a transition point in the pelvis. Exploration revealed a small bowel mass located approximately 12 cm from the ileocecal valve. Pathological analysis showed large malignant cells with a high ...

Precision Medicine For Crc Patients In The Veteran Population: State-Of-The-Art, Challenges And Research Directions., Shyam S Mohapatra, Surinder K Batra, Srinivas Bharadwaj, Michael Bouvet, Bard Cosman, Ajay Goel, Wilma Jogunoori, Michael J Kelley, Lopa Mishra, Bibhuti Mishra, Subhra Mohapatra, Bhaumik Patel, Joseph R Pisegna, Jean-Pierre Raufman, Shuyun Rao, Hemant Roy, Maren Scheuner, Satish Singh, Gitanjali Vidyarthi, Jon White

Surgery Faculty Publications

Colorectal cancer (CRC) accounts for ~9% of all cancers in the Veteran population, a fact which has focused a great deal of the attention of the VA's research and development efforts. A field-based meeting of CRC experts was convened to discuss both challenges and opportunities in precision medicine for CRC. This group, designated as the VA Colorectal Cancer Cell-genomics Consortium (VA4C), discussed advances in CRC biology, biomarkers, and imaging for early detection and prevention. There was also a discussion of precision treatment involving fluorescence-guided surgery, targeted chemotherapies and immunotherapies, and personalized cancer treatment approaches. The overarching goal was to ...