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Chronical pancreatitis

Kavitha Yuvaraj, Arumugam Geetha
Background Chronic pancreatitis (CP) is a persistent inflammation of the pancreas clinically presented with severe abdominal pain, progressive fibrosis, and loss of exocrine and endocrine functions. Inflammasomes, cytosolic multiprotein complexes which regulate the formation of proinflammatory cytokines, are influenced by various factors including heat shock proteins (HSPs). Morus alba L., or white mulberry root bark is a valued traditional Asian medicine with a diverse array of phytochemicals. The aim of this investigation was to define the modulatory action of methanolic extract of Morus alba root bark (MEMARB) on NLRP3 inflammasome, and HSPs in pancreas subjected to inflammatory insult...
October 18, 2018: Journal of Complementary & Integrative Medicine
Jin Song, Lori J Sokoll, Jered J Pasay, Abigail L Rubin, Hanying Li, Dylan M Bach, Daniel W Chan, Zhen Zhang
BACKGROUND: Pancreatic cancer is a deadly disease for which available biomarkers, such as CA19-9, lack the desired sensitivity and specificity for early detection. Additional biomarkers are needed to improve both its sensitivity and specificity. METHODS: Multiplex immunoassays were developed for selected biomarkers using a Bio-Plex 200 system and analytical performance optimized. All proteins were analyzed in sera of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC, n=188) or benign pancreatic conditions (131), and healthy controls (89)...
October 17, 2018: Cancer Epidemiology, Biomarkers & Prevention
Soheila Maghami, Homeira Zardooz, Fariba Khodagholi, Fatemeh Binayi, Roya Ranjbar Saber, Mehdi Hedayati, Hedayat Sahraei, Mohammad Ali Ansari
This study explores the effects of maternal separation as a chronic early life stress (ELS) on pancreatic islets insulin content and secretion, and their potential relationship with the hippocampus insulin content and spatial memory in young adulthood. Male rat offspring were divided into two groups: stress (STR) and non-stress (non-STR) groups. The animals of the STR group were separated from their mothers during postnatal days (PND) 1 to 21. During the weaning time, that is, PND-0 to PND-21, the body weight and length of the pups were measured...
2018: PloS One
Zoltan Rumbus, Emese Toth, Laszlo Poto, Aron Vincze, Gabor Veres, Laszlo Czako, Emoke Olah, Katalin Marta, Alexandra Miko, Zoltan Rakonczay, Zsolt Balla, Jozsef Kaszaki, Imre Foldesi, Jozsef Maleth, Peter Hegyi, Andras Garami
Acute pancreatitis (AP) is often accompanied by alterations in the acid-base balance, but how blood pH influences the outcome of AP is largely unknown. We studied the association between blood pH and the outcome of AP with meta-analysis of clinical trials, and aimed to discover the causative relationship between blood pH and AP in animal models. PubMed, EMBASE, and Cochrane Controlled Trials Registry databases were searched from inception to January 2017. Human studies reporting systemic pH status and outcomes (mortality rate, severity scores, and length of hospital stay) of patient groups with AP were included in the analyses...
2018: Frontiers in Physiology
Emilie Courty, Adrien Besseiche, Thi Thu Huong Do, Alexandrine Liboz, Fatima Mohamed Aguid, Evans Quilichini, Melissa Buscato, Pierre Gourdy, Jean-François Gautier, Jean-Pierre Riveline, Cécile Haumaitre, Marion Buyse, Bruno Fève, Ghislaine Guillemain, Bertrand Blondeau
Both type 1 and 2 diabetes are characterized by deficient insulin secretion and decreased beta-cell mass. Thus, regenerative strategies to increase beta-cell mass need to be developed. To characterize mechanisms of beta-cell plasticity, we studied a model of severe insulin resistance in the adult mouse and defined how beta cells adapt. Chronic corticosterone (CORT) treatment was given to adult mice and led to rapid insulin resistance and adaptive increased insulin secretion. Adaptive and massive increase of beta-cell mass was observed during treatment up to 8 weeks...
October 16, 2018: Diabetes
Anirban Maitra, Ayush Sharma, Randall E Brand, Stephen K Van Den Eeden, William E Fisher, Phil A Hart, Steven J Hughes, Kieren J Mather, Stephen J Pandol, Walter G Park, Ziding Feng, Jose Serrano, Jo Ann S Rinaudo, Sudhir Srivastava, Suresh T Chari
The National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases initiated the Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer (CPDPC) in 2015 (the CPDPC's origin, structure, governance, and research objectives are described in another article in this journal). One of the key objectives of CPDPC is to assemble a cohort of 10,000 subjects 50 years or older with new-onset diabetes, called the NOD cohort. Using a define, enrich, and find early detection approach, the aims of the NOD study are to (a) estimate the 3-year probability of pancreatic ductal adenocarcinoma (PDAC) in NOD (define), (b) establish a biobank of clinically annotated biospecimens from presymptomatic PDAC and control new-onset type 2 diabetes mellitus subjects, (c) conduct phase 3 validation studies of promising biomarkers for identification of incident PDAC in NOD patients (enrich), and (d) provide a platform for development of a future interventional screening protocol for early detection of PDAC in patients with NOD that incorporates imaging studies and/or clinical algorithms (find)...
November 2018: Pancreas
Phil A Hart, Dana K Andersen, Kieren J Mather, Alicia C Castonguay, Mandeep Bajaj, Melena D Bellin, David Bradley, Noemy Contreras, Aida Habtezion, Murray Korc, Yogish Kudva, Maxim S Petrov, David C Whitcomb, Dhiraj Yadav, Ying Yuan, Jo Ann S Rinaudo, Sudhir Srivastava, Jose Serrano, Mark O Goodarzi
Pancreatogenic diabetes mellitus is most commonly the result of chronic pancreatitis but can also occur secondary to pancreatic cancer. The early identification of pancreatogenic diabetes and distinction from the more prevalent type 2 diabetes are clinically significant; however, currently, there is no validated method to differentiate these diabetes subtypes. We describe a study, "Evaluation of a Mixed Meal Test for Diagnosis and Characterization of PancrEaTogEniC DiabeTes Secondary to Pancreatic Cancer and Chronic Pancreatitis: the DETECT study," that seeks to address this knowledge gap...
November 2018: Pancreas
Dhiraj Yadav, Walter G Park, Evan L Fogel, Liang Li, Suresh T Chari, Ziding Feng, William E Fisher, Christopher E Forsmark, Christie Y Jeon, Aida Habtezion, Phil A Hart, Steven J Hughes, Mohamed O Othman, Jo Ann S Rinaudo, Stephen J Pandol, Temel Tirkes, Jose Serrano, Sudhir Srivastava, Stephen K Van Den Eeden, David C Whitcomb, Mark Topazian, Darwin L Conwell
Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies (PROCEED) is the first prospective, observational cohort study of chronic pancreatitis (CP) in the United States. The primary goals of PROCEED are to define disease progression, test the predictive capability of candidate biomarkers, and develop a platform to conduct translational and mechanistic studies in CP. Using objective and consensus-driven criteria, PROCEED will enroll adults at different stages of CP-controls, suspected CP, and definite CP...
November 2018: Pancreas
Aliye Uc, Emily R Perito, John F Pohl, Uzma Shah, Maisam Abu-El-Haija, Bradley Barth, Melena D Bellin, Kate M Ellery, Douglas S Fishman, Cheryl E Gariepy, Matthew J Giefer, Tanja Gonska, Melvin B Heyman, Ryan W Himes, Sohail Z Husain, Asim Maqbool, Maria R Mascarenhas, Brian A McFerron, Veronique D Morinville, Tom K Lin, Quin Y Liu, Jaimie D Nathan, Sue J Rhee, Chee Y Ooi, Zachary M Sellers, Sarah Jane Schwarzenberg, Jose Serrano, David M Troendle, Steven L Werlin, Michael Wilschanski, Yuhua Zheng, Ying Yuan, Mark E Lowe
We created the INternational Study Group of Pediatric Pancreatitis: In Search for a CuRE (INSPPIRE 2) cohort to study the risk factors, natural history, and outcomes of pediatric acute recurrent pancreatitis and chronic pancreatitis (CP). Patient and physician questionnaires collect information on demographics, clinical history, family and social history, and disease outcomes. Health-related quality of life, depression, and anxiety are measured using validated questionnaires. Information entered on paper questionnaires is transferred into a database managed by Consortium for the Study of Chronic Pancreatitis, Diabetes, and Pancreatic Cancer's Coordinating and Data Management Center...
November 2018: Pancreas
William E Fisher, Zobeida Cruz-Monserrate, Amy L McElhany, Gregory B Lesinski, Phil A Hart, Ria Ghosh, George Van Buren, Douglas S Fishman, Jo Ann S Rinaudo, Jose Serrano, Sudhir Srivastava, Thomas Mace, Mark Topazian, Ziding Feng, Dhiraj Yadav, Stephen J Pandol, Steven J Hughes, Robert Y Liu, Emily Lu, Robert Orr, David C Whitcomb, Amer S Abouhamze, Hanno Steen, Zachary M Sellers, David M Troendle, Aliye Uc, Mark E Lowe, Darwin L Conwell
High-quality and well-annotated biorepositories are needed to better understand the pathophysiology and biologic mechanisms of chronic pancreatitis (CP) and its consequences. We report a methodology for the development of a robust standard operating procedure (SOP) for a biorepository based on the experience of the clinical centers within the consortium to study Chronic Pancreatitis, Diabetes and Pancreas Cancer Clinical Centers (CPDPC), supported by the National Cancer Institute and the National Institute for Diabetes and Digestive and Kidney Diseases as a unique multidisciplinary model to study CP, diabetes, and pancreatic cancer in both children and adults...
November 2018: Pancreas
Jose Serrano, Dana K Andersen, Christopher E Forsmark, Stephen J Pandol, Ziding Feng, Sudhir Srivastava, Jo Ann S Rinaudo
Research progress in diseases of the exocrine pancreas [chronic pancreatitis (CP), pancreatogenic diabetes mellitus, and pancreatic cancer] has been hampered by the disorders' heterogeneity, the limitations of previous small cross-sectional studies, the inability to safely obtain pancreatic tissue for study, and the lack of structured epidemiology tools, genetic testing, and biomarker development. Mechanism-based research of these diseases has suffered from the lack of systematically collected clinical measures in longitudinal cohort studies linked with biospecimens...
November 2018: Pancreas
Christopher E Forsmark, Dana K Andersen, John T Farrar, Megan Golden, Aida Habtezion, Sohail Z Husain, Liang Li, Julia Mayerle, Stephen J Pandol, Aliye Uc, Zixi Zhu, Dhiraj Yadav
The lack of effective therapeutic agents specifically tailored for chronic pancreatitis (CP) has hampered clinical care and negatively impacted patients' lives. New mechanistic insights now point to novel therapies, which involve both recently developed and/or repurposed agents. This working group focused on 2 main outcomes for CP: pain and progression of disease. The goal is to frame the essential aspects of trial design including patient-centered outcomes, proposed methods to measure the outcomes of pain and progression, and study design considerations for future trials to facilitate rapid drug development for patients with CP...
November 2018: Pancreas
Mark E Lowe, Marc T Goodman, Gregory A Coté, Marshall J Glesby, Mark Haupt, Nicholas J Schork, Vikesh K Singh, Dana K Andersen, Stephen J Pandol, Aliye Uc, David C Whitcomb
Recurrent acute pancreatitis (RAP) is a complex clinical syndrome with significant morbidity, unpredictable outcomes, and limited treatment options. The National Institute of Diabetes and Digestive and Kidney Disease sponsored a workshop on July 25, 2018, in Pittsburgh, Pennsylvania, to address research gaps impeding development of effective therapies for pancreatitis. The RAP working group identified challenges to clinical progress using existing definitions, risk assessment, diagnostic and severity criteria, disease trajectories, outcomes, and research methods...
November 2018: Pancreas
Maisam Abu-El-Haija, Anna S Gukovskaya, Dana K Andersen, Timothy B Gardner, Peter Hegyi, Stephen J Pandol, Georgios I Papachristou, Ashok K Saluja, Vikesh K Singh, Aliye Uc, Bechien U Wu
A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to focus on research gaps and opportunities on drug development for pancreatitis. This conference was held on July 25, 2018, and structured into 3 working groups (WG): acute pancreatitis (AP) WG, recurrent AP WG, and chronic pancreatitis WG. This article reports the outcome of the work accomplished by the AP WG to provide the natural history, epidemiology, and current management of AP; inform about the role of preclinical models in therapy selection; and discuss clinical trial designs with clinical and patient-reported outcomes to test new therapies...
November 2018: Pancreas
Aliye Uc, Dana K Andersen, Drucy Borowitz, Marshall J Glesby, Julia Mayerle, Robert Sutton, Stephen J Pandol
A workshop was sponsored by the Division of Digestive Diseases and Nutrition, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, on July 25, 2018, in Pittsburgh, Penn. The workshop was designed to bring together a multidisciplinary group of experts to accelerate the development of therapeutics for clinical application in inflammatory diseases of the exocrine pancreas. Three separate working groups (acute pancreatitis, recurrent acute pancreatitis, and chronic pancreatitis) were formed to address the needs, gaps, and opportunities...
November 2018: Pancreas
Temel Tirkes, Zarine K Shah, Naoki Takahashi, Joseph R Grajo, Stephanie T Chang, Sudhakar K Venkatesh, Darwin L Conwell, Evan L Fogel, Walter Park, Mark Topazian, Dhiraj Yadav, Anil K Dasyam
Chronic pancreatitis is an inflammatory condition of the pancreas with clinical manifestations ranging from abdominal pain, acute pancreatitis, exocrine and/or endocrine dysfunction, and pancreatic cancer. There is a need for longitudinal studies in well-phenotyped patients to ascertain the utility of cross-sectional imaging findings of chronic pancreatitis for diagnosis and assessment of disease severity. CT and MR cholangiopancreatography are the most common cross-sectional imaging studies performed for the evaluation of chronic pancreatitis...
October 16, 2018: Radiology
Alec J Megibow
See also the article by Tirkes et al in this issue.
October 16, 2018: Radiology
Ana S Leal, Karen T Liby
Chronic or repeated episodes of acute pancreatic inflammation, or pancreatitis, are risk factors for the development of pancreatic cancer. Pancreatic cancer is characterized by a strong fibro-inflammatory tumor microenvironment. In pancreatitis, the same fibro-inflammatory reaction is observed concurrently with a loss of normal pancreatic cells. Mouse models are commonly employed to study the progression of pancreatitis and pancreatic cancer, with genetic and pharmacological tools used to elucidate cellular and acellular interactions within pancreatic tumors...
October 16, 2018: Current Protocols in Pharmacology
Tomasz Bodnarczuk, Anna Deskur, Katarzyna Dolegowska, Barbara Dolegowska, Teresa Starzynska, Wojciech Blogowski
Previous experimental reports have demonstrated that lipoxygenase (LOX) derivatives of arachidonic acid (AA), such as hydroxyeicosatetraenoic acids (HETEs), may be of significance in the pathogenesis of pancreatic cancer. However, these observations have not been confirmed in clinical studies. In the current study, we comprehensively evaluated the systemic levels of selected LOX-derived HETEs such as 5-, 12- and 15-HETE in patients with pancreatic adenocarcinoma (n=36), chronic pancreatitis (n=39), and in healthy individuals (n=35)...
2018: American Journal of Cancer Research
Serena Stigliano, Alexander Waldthaler, Emma Martinez-Moneo, Luana Lionetto, Stuart Robinson, Marko Malvik, Aleksandra Hedstrom, Aleksandra Kaczka, Marius Scholdei, Stephan Haas, Maurizio Simmaco, Gianfranco Delle Fave, Matthias Lohr, Peter Simon, Gabriele Capurso
BACKGROUND: Osteopathy is common in patients with chronic pancreatitis (CP), but previous studies carry several limitations. Vitamin K is essential for bone metabolism, but its role in this setting has never been investigated. Our aim is to assess the prevalence of osteoporosis and osteopenia in CP patients, and to investigate the association between osteopathy and CP features and nutritional parameters, especially vitamin D and K levels. METHODS: Multicentre cross-sectional study on CP patients diagnosed according to M-ANNHEIM criteria...
October 15, 2018: Clinical and Translational Gastroenterology
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