Digestive System Diseases Commons^™

Pediatric Inflammatory Bowel Disease Tissue Classification From Pathology Slide Images: Detecting Phenotypes Using Computer Vision, Chloe Martin-King, Ali Nael, Louis Ehwerhemuepha, Blake Calvo, Quinn Gates, Jamie Janchoi, Elisa Ornelas, Melissa Perez, Andrea Venderby, John Miklavcic, Peter Chang, Aaron Sassoon, Brian Rubio, Ghislaine Barrigan, Kenneth Grant

Food Science Faculty Articles and Research

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Background and Aims

With the advent of computer vision algorithms, we hypothesize that histopathology images from endoscopic biopsies may be utilized for automated classification of histologic phenotypes, thus guiding Crohn’s disease and ulcerative colitis diagnosis and treatment. The aim of our study is to assess whether artificial intelligence can be used to improve pediatric inflammatory bowel disease outcomes by aiding pathologists with accurate detection of abnormal tissue sections.

Methods

Three two-dimensional (2D) convolutional neural networks with multiple instance learning were developed to classify histopathology tissue sections as normal vs abnormal and as containing active inflammation and/or chronic changes/architectural distortion.

Results …

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Hepatocyte-Specific Lrp1 Silencing Exacerbates Brain Amyloidosis Without Compensatory Ldl Receptor Family Involvement, Brian Carson, Josephine Chu, Devaraj V. Chandrashekar, Jerome Garcia, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

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Background

LDL receptor related protein 1 (LRP1) is a major hepatic receptor involved in lipoprotein metabolism, protease degradation, transmembrane receptor modulation, and clearance of excess protein, such as Aβ. Decreased expression of LRP1 due to liver injury can impair receptor-mediated clearance, increasing Aβ availability in the periphery. We investigated the effects of hepato-specific silencing of LRP1 on Aβ deposition in the brain. Additionally, other LDL family members (LRP5, LRP6, and LDLR) that may participate in Aβ clearance were monitored in the liver to ensure non-compensatory effects of LRP1 silencing.

Method

4-month-old male double transgenic (APP/PS1) AD mice were injected with …

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The Mitochondria Is The Source Of Hepatic Amyloid Precursor Protein And Peripheral Amyloid Beta: Implications Of Alcohol-Induced Liver Steatosis In Alzheimer's Disease, Josephine Chu, Ross A. Steinberg, Brian Carson, Devaraj Venkatapura Chandrashekar, Rachita K. Sumbria, Derick Han

Pharmacy Faculty Articles and Research

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Background

Alcohol-induced liver injury occurs in the pericentral region of the liver and can induce mitochondrial remodeling and exacerbate Alzheimer's Disease (AD) progression. Subpopulations of mitochondria: general mitochondria (GM), peridroplet mitochondria (PDM) and endoplasmic reticulum(ER)-bound mitochondria (ERM) maintain cellular homeostasis via energy synthesis, lipid homeostasis, and regulation of intracellular calcium. Hepatic amyloid precursor protein (APP) is a source of peripheral amyloid beta (aB) and affects AD pathology in the brain. Understanding the localization and expression of hepatic APP in mitochondrial subpopulations are critical to understanding aB metabolism and may play a role in identifying a potential mechanism for metabolic dysfunction. …

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Effects Of Liver Surgery On Drug Transporters In The Liver And Remote Organs, Reza Mehvar

Pharmacy Faculty Articles and Research

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Alterations in drug transporters in acute liver failure and chronic liver diseases, such as cirrhosis, have been reviewed before. However, there is a lack of comprehensive reviews on how liver surgery, including transplantation and partial hepatectomy, affects drug transporters. Because ischemia–reperfusion (IR) injury is a hallmark of liver transplantation and most other surgical procedures of the liver, this review focuses on the effects of IR injury, in addition to liver resection, on the expression and function of transporters in the liver and remote organs. Most of the reported studies in this area are carried out in animal models of liver …

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Combination Of Irreversible Electroporation And Clostridium Novyi-Nt Bacterial Therapy For Colorectal Liver Metastasis, Zigeng Zhang, Guangbo Yu, Qiaoming Hou, Farideh Amirrad, Sha Webster, Surya M. Nauli, Jianhua Yu, Vahid Yaghmai, Aydin Eresen, Zhuoli Zhang

Pharmacy Faculty Articles and Research

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Colorectal liver metastasis (CRLM) poses a significant challenge in oncology due to its high incidence and poor prognosis in unresectable cases. Current treatments, including surgical resection, systemic chemotherapy, and liver-directed therapies, often fail to effectively target hypoxic tumor regions, which are inherently more resistant to these interventions. This review examines the potential of a novel therapeutic strategy combining irreversible electroporation (IRE) ablation and Clostridium novyi-nontoxic (C. novyi-NT) bacterial therapy. IRE is a non-thermal tumor ablation technique that uses high-voltage electric pulses to create permanent nanopores in cell membranes, leading to cell death while preserving surrounding structures, and …

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1st Place Contest Entry: Effectiveness Of Intravesical Bcg In The Treatment Of Nonmuscle Invasive Bladder Cancer: An Umbrella Review, Gerald Obinna Ozota

Eric M. Scandrett Graduate Library Research Prize

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This is Gerald Obinna Ozota's submission for the 2025 Eric M. Scandrett Graduate Research Prize, which won first place. It contains their essay on using library resources, their bibliography, and a summary of their research project on conducting a systematic literature search to identify all relevant systematic reviews and meta-analyses investigating the effectiveness of intravesical Bacillus Calmette-Guerin (BCG) on Non-muscle-invasive Bladder Cancer (NIMBC).

Gerald is a student in the Ph.D. in Pharmaceutical Sciences program at Chapman University. Their faculty mentor is Dr. Lawrence Brown.

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Effect Of Chronic Alcohol Feeding Using The Lieber-Decarli Diet On Alzheimer’S Disease Pathology In Tg2576 Mice, Devaraj V. Chandrashekar, Nataraj Jagadeesan, Tamara Abdullah, Rudy Chang, Ross A. Steinberg, Frankey Sanchez, Elias Khal, Joshua Yang, David H. Cribbs, Derick Han, Rachita K. Sumbria

Pharmacy Faculty Articles and Research

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Background: Chronic alcohol drinking is a modifiable risk factor for Alzheimer’s disease (AD), but underlying mechanisms remain poorly understood. Most studies of alcohol feeding to AD mice have utilized young mice and delivered alcohol in drinking water without controlling nutritional intake.

Objective: To study the impact of Lieber-DeCarli (LDC) liquid alcohol diet, which balances nutritional intake, on AD pathology of aged Tg2576 and wild-type (WT) mice, which is unexplored.

Methods: 13-month-old male and female Tg2576 or WT mice were fed LDC diet (5% ethanol or control) for six weeks (n = 11-13/group). Exploration (open-field test) and spatial reference memory …

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Cracking The Code Of Hbv Persistence: Cutting-Edge Approaches To Targeting Cccdna In Chronic Hepatitis B With Or Without Pyogenic Liver Abscesses, Umar Saeed, Zahra Zahid Piracha, Mahmood Khan, Muhammad Nouman Tariq, Syed Shahan Gilani, Muhammad Raza, Rakshana Munuswamy, Naveen Bose, Dilber Uzun Ozsahin, Ilker Özşahin, Surya M. Nauli

Pharmacy Faculty Articles and Research

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Chronic Hepatitis B Virus (HBV) infection remains a formidable global health challenge, driving severe liver complications such as hepatocellular carcinoma (HCC) and pyogenic liver abscesses (PLA). At the core of HBV persistence lies covalently closed circular DNA (cccDNA), a viral reservoir that fuels ongoing infection despite antiviral treatments. This review highlights molecular mechanisms governing cccDNA formation, maintenance, and clearance, spotlighting innovative therapeutic strategies to disrupt this key viral element. We explore cutting-edge approaches, including epigenetic modulation to silence cccDNA, RNA interference (RNAi) for viral RNA degradation, and CRISPR/Cas genome editing to excise cccDNA directly. Additionally, emerging antiviral therapies and immunotherapies, …

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Bile Duct Ligation-Induced Cirrhosis Does Not Alter The Blood-Brain Barrier Permeability To Sucrose In Rats, Mohammad K. Miah, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

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Contradictory results have been reported about the effects of liver diseases on the blood-brain barrier (BBB) permeability to markers. For instance, both an increase and no change in the BBB permeability to BBB markers sodium fluorescein and Evans blue have been reported in experimental cholestasis induced by bile duct ligation (BDL) in rats. These contradictory effects might be due to inherent limitations of these markers and/or methodological issues. Here, we investigated the time course of the impact of BDL in rats on BBB permeability using a recently developed stable isotope labeled marker [¹³C]sucrose, which is expected to be …

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Predicting And Monitoring Immune Checkpoint Inhibitor Therapy Using Artificial Intelligence In Pancreatic Cancer, Guangbo Yu, Zigeng Zhang, Aydin Eresen, Qiaoming Hou, Farideh Amirrad, Sha Webster, Surya M. Nauli, Vahid Yaghmai, Zhuoli Zhang

Pharmacy Faculty Articles and Research

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Pancreatic cancer remains one of the most lethal cancers, primarily due to its late diagnosis and limited treatment options. This review examines the challenges and potential of using immunotherapy to treat pancreatic cancer, highlighting the role of artificial intelligence (AI) as a promising tool to enhance early detection and monitor the effectiveness of these therapies. By synthesizing recent advancements and identifying gaps in the current research, this review aims to provide a comprehensive overview of how AI and immunotherapy can be integrated to develop more personalized and effective treatment strategies. The insights from this review may guide future research efforts …

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Histopathology Imaging And Clinical Data Including Remission Status In Pediatric Inflammatory Bowel Disease, Chloe Martin-King, Ali Nael, Louis Ehwerhemuepha, Blake Calvo, Quinn Gates, Jamie Janchoi, Elisa Ornelas, Melissa Perez, Andrea Venderby, John Miklavcic, Peter Chang, Aaron Sassoon, Kenneth Grant

Food Science Faculty Articles and Research

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The incidence of inflammatory bowel disease (IBD) is increasing annually. Children with IBD often suffer significant morbidity due to physical and emotional effects of the disease and treatment. Corticosteroids, often a component of therapy, carry undesirable side effects with long term use. Steroid-free remission has become a standard for care-quality improvement. Anticipating therapeutic outcomes is difficult, with treatments often leveraged in a trial-and-error fashion. Artificial intelligence (AI) has demonstrated success in medical imaging classification tasks. Predicting patients who will attain remission will help inform treatment decisions. The provided dataset comprises 951 tissue section scans (167 whole-slides) obtained from 18 pediatric …

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Non-Alcoholic Fatty Liver Disease: Role Of Pnpla3 And Its Association With Environmental Chemicals, Shakil A. Saghir, Ata Abbas, Saleh Alfuraih, Ajay Sharma, Jean Latimer, Yadollah Omidi, Rais Ansari

Pharmacy Faculty Articles and Research

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Globally, non-alcoholic fatty liver disease (NAFLD) is on the rise with 30-32%, 27-33%, 35-48%, 36%, 9-20%, and 36-38% prevalence in Asia, Europe, North America, South America, Africa, and Australia, respectively. Approximately, 5-10% of NAFLD proceeds to hepatitis called non-alcoholic steatohepatitis (NASH). NASH often progresses to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Precise mechanism(s) for the development of HCC is not fully understood in NAFLD and NASH patients. Higher insulin levels in type 2 diabetes (T2D) can result in lipolysis of adipose tissue activating lipid synthesizing enzymes such as fatty acid synthase and stearoyl-CoA desaturase-1, resulting in lipid accumulation in …

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Classification Of Colorectal Cancer Using Resnet And Efficientnet Models, Abhishek Ranjan, Priyanshu Srivastva, B Prabadevi, R Sivakumar, Rahul Soangra, Shamala K. Subramaniam

Physical Therapy Faculty Articles and Research

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Introduction:

Cancer is one of the most prevalent diseases from children to elderly adults. This will be deadly if not detected at an earlier stage of the cancerous cell formation, thereby increasing the mortality rate. One such cancer is colorectal cancer, caused due to abnormal growth in the rectum or colon. Early screening of colorectal cancer helps to identify these abnormal growth and can exterminate them before they turn into cancerous cells.

Aim:

Therefore, this study aims to develop a robust and efficient classification system for colorectal cancer through Convolutional Neural Networks (CNNs) on histological images.

Methods:

Despite challenges in …

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Non-Alcoholic Fatty Liver Disease: Genetic Susceptibility, Shakil A. Saghir, Nicole Shams, Lianette Veliz, Saleh Alfuraih, Yadollah Omidi, Jaleh Barar, Ajay Sharma, Rais Ansari

Pharmacy Faculty Articles and Research

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The prevalence of Non-alcoholic Fatty Liver Disease (NAFLD) is increasing, particularly in individuals who consume minimal to no alcohol. Currently, NAFLD affects at least 32% of the global population. Although not all but approximately 5-10% cases of NAFLD progress to non-alcoholic steatohepatitis (NASH), a condition arising from lipotoxicity. Patients with NASH may further develop liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). However, it is important to note that progression from NAFLD to NASH and HCC is not inevitable for all patients. The pathogenesis of HCC in the context of NAFLD and NASH remains poorly understood, however, fat accumulation, often due …

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Split And Join: An Efficient Approach For Simulating Stapled Intestinal Anastomosis In Virtual Reality, Di Qi, Suvranu De

Engineering Faculty Articles and Research

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Colorectal cancer is a life-threatening disease. It is the second leading cause of cancer-related deaths in the United States. Stapled anastomosis is a rapid treatment for colorectal cancer and other intestinal diseases and has become an integral part of routine surgical practice. However, to the best of our knowledge, there is no existing work simulating intestinal anastomosis that often involves sophisticated soft tissue manipulations such as cutting and stitching. In this paper, for the first time, we propose a novel split and join approach to simulate a side-to-side stapled intestinal anastomosis in virtual reality. We mimic the intestine model using …

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Effects Of Chronic Cirrhosis Induced By Intraperitoneal Thioacetamide Injection On The Protein Content And Michaelis–Menten Kinetics Of Cytochrome P450 Enzymes In The Rat Liver Microsomes, Devaraj Venkatapura Chandrashekar, Barent N. Dubois, Mamunur Rashid, Reza Mehvar

Pharmacy Faculty Articles and Research

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Chronic intraperitoneal injection of thioacetamide (TAA) in rats has been used as an animal model of human cirrhosis to study the effects of the disease on drug metabolism. However, TAA inhibits P450 enzymes directly and independently of cirrhosis. We investigated the effects of chronic cirrhosis in rats, induced by 10 weeks of intraperitoneal TAA, on the P450 enzymes after a 10-day washout period to eliminate TAA. Liver histology and serum biomarkers of hepatic function confirmed cirrhosis in all animals. Microsomal total P450 content, P450 reductase activity and ethoxycoumarin O-deethylase activity, a general marker of P450 activity, were significantly reduced by …

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Enhancing Microbiome Host Disease Prediction With Variational Autoencoders, Celeste Manughian-Peter

Computational and Data Sciences (MS) Theses

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Advancements in genetic sequencing methods for microbiomes in recent decades have permitted the collection of taxonomic and functional profiles of microbial communities, accelerating the discovery of the functional aspects of the microbiome and generating an increased interest among clinicians in applying these techniques with patients. This advancement has coincided with software and hardware improvements in the field of machine learning and deep learning. Combined, these advancements implicate further potential for progress in disease diagnosis and treatment in humans. The ability to classify a human microbiome profile into a disease category, and additionally identify the differentiating factors within the profile between …

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Ganglioside Alters Phospholipase Trafficking, Inhibits Nf-Κb Assembly, And Protects Tight Junction Integrity, John J. Miklavcic, Qun Li, Jordan Skolnick, Alan B. R. Thomson, Vera C. Mazurak, Michael Tom Clandinin

Food Science Faculty Articles and Research

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Background and Aims: Dietary gangliosides are present in human milk and consumed in low amounts from organ meats. Clinical and animal studies indicate that dietary gangliosides attenuate signaling processes that are a hallmark of inflammatory bowel disease (IBD). Gangliosides decrease pro-inflammatory markers, improve intestinal permeability, and reduce symptoms characteristic in patients with IBD. The objective of this study was to examine mechanisms by which dietary gangliosides exert beneficial effects on intestinal health.

Methods: Studies were conducted in vitro using CaCo-2 intestinal epithelial cells. Gangliosides were extracted from milk powder and incubated with differentiated CaCo-2 cells after exposure to pro-inflammatory stimuli. …

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Predictors Of Hepatitis C Testing Intention Among African American Baby Boomers, Mohamed Rashrash, Mary Maneno, Anthony Wutoh, Earl Ettienne, Monica Daftary

Pharmacy Faculty Articles and Research

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Baby Boomers (BBs) are responsible for three-quarters of hepatitis C virus (HCV) infections in the United States; however, HCV testing is distinctly underused by them. A cross-sectional study was conducted to assess the prevalence of HCV testing and to evaluate predictors of HCV testing intention among African– American BBs. The study was guided by the Health Belief Model and theory of reasoned action frameworks. Of the 137 participants included in the study, 44.8% had at least a college education; 13.9% received prior to 1992 blood transfusion. Findings related to HCV testing showed that 32.1% of the participants intended to test …

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Effects Of Pringle Maneuver And Partial Hepatectomy On The Pharmacokinetics And Blood–Brain Barrier Permeability Of Sodium Fluorescein In Rats, Mohammad K. Miah, Imam H. Shaik, Ulrich Bickel, Reza Mehvar

Pharmacy Faculty Articles and Research

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Liver diseases are known to affect the function of remote organs. The aim of the present study was to investigate the effects of Pringle maneuver, which results in hepatic ischemia–reperfusion (IR) injury, and partial hepatectomy (Hx) on the pharmacokinetics and brain distribution of sodium fluorescein (FL), which is a widely used marker of blood–brain barrier (BBB) permeability. Rats were subjected to Pringle maneuver (total hepatic ischemia) for 20 min with (HxIR) or without (IR) 70% hepatectomy. Sham-operated animals underwent laparotomy only. After 15 min or 8 h of reperfusion, a single 25-mg/kg dose of FL was injected intravenously and serial …

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Vaccine-Preventable Diseases In Travelers, Edith Mirzaian, Jeffery A. Goad, Ani Amloian, Fady Makar

Pharmacy Faculty Articles and Research

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Travel to the developing world is increasing among those from developed countries, placing them at risk for vaccine preventable and non-vaccine preventable diseases. From 2007-2011, the GeoSentinel Network reported 737 returned travelers with a vaccine preventable disease. While it is essential that clinicians use vaccines when available for a disease of risk, they should also be aware that the vast majority of diseases acquired by travelers are non-vaccine preventable. The vaccine preventable diseases can be divided into routine travel vaccines, special travel vaccines and routine vaccines used for travel. The routine travel vaccines include Hepatitis A and B, typhoid; special …

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Effects Of Methylprednisolone And Its Liver-Targeted Dextran Prodrug On Ischemia–Reperfusion Injury In A Rat Liver Transplantation Model, Anjaneya Chimalakonda, Reza Mehvar

Pharmacy Faculty Articles and Research

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Purpose. To evaluate the effectiveness of a liver-targeted dextran prodrug (DMP) of methylprednisolone ( MP) in cold preservation-warm reperfusion injury associated with liver transplantation.

Methods. The effects of donor pretreatment with single 5 mg/kg doses of MP or DMP on ischemia reperfusion damage to the liver were studied after 8 or 24 h of cold preservation in both isolated perfused rat liver (IPRL) and syngeneic orthotopic rat liver transplantation (OLT) models.

Results. In IPRL studies, donor pretreatment with DMP, and to a lesser degree MP, significantly improved the uptake of hyaluronic acid (HA), a marker of endothelial …

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Attenuation Of Acute Rejection In A Rat Liver Transplantation Model By A Liver-Targeted Dextran Prodrug Of Methylprednisolone, Anjaneya Chimalakonda, Donald L. Montgomery, Jon A. Weidanz, Imam H. Shaik, Justin H. Nguyen, John J. Lemasters, Eiji Kobayashi, Reza Mehvar

Pharmacy Faculty Articles and Research

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Background. The use of methylprednisolone (MP) and other corticosteroids for the treatment of acute liver allograft rejection is associated with severe toxicities in nontarget tissues. Therefore, selective delivery of NIP to the liver may improve its efficacy and alleviate its side effects. We investigated the effects of a novel liver-targeted dextran prodrug of MP (DMP) in an orthotopic rat liver transplantation (OLT) model.

Methods. The model consisted of a high responder rejection strain combination (Dark Agouti donors and Lewis recipients). Liver recipients were intravenously administered saline or a single subtherapeutic dose of MP (5 mg/kg) as the parent …

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