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https://www.readbyqxmd.com/read/28213892/opportunities-for-repurposing-of-poly-adp-ribose-polymerase-parp-inhibitors-for-the-therapy-of-non-oncological-diseases
#1
REVIEW
Nathan A Berger, Valerie C Besson, A Hamid Boulares, Alexander Bürkle, Alberto Chiarugi, Robert S Clark, Nicola J Curtin, Salvatore Cuzzocrea, Ted M Dawson, Valina L Dawson, György Haskó, Lucas Liaudet, Flavio Moroni, Pál Pacher, Peter Radermacher, Andrew L Salzman, Solomon H Snyder, Francisco Garcia Soriano, Robert P Strosznajder, Balázs Sümegi, Raymond A Swanson, Csaba Szabo
The recent clinical availability of the PARP inhibitor Lynparza (olaparib) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, indications where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, provide first-line options for therapeutic repurposing...
February 18, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28213644/circulating-micrornas-and-diabetes-mellitus-a-novel-tool-for-disease-prediction-diagnosis-and-staging
#2
REVIEW
G Sebastiani, L Nigi, G E Grieco, F Mancarella, G Ventriglia, F Dotta
Diabetes is a complex, multifactorial group of metabolic diseases characterized by chronic hyperglycaemia due to pancreatic beta-cell dysfunction and/or loss. It is characterized by an asymptomatic and highly variable prodromic phase, which renders diabetes mellitus difficult to be predicted with sufficient accuracy. Despite several efforts in the identification and standardization of newly trustable. Biomarkers able to predict and follow-up diabetes and to specifically subtype its different forms, few of them have proven of clinical utility...
February 17, 2017: Journal of Endocrinological Investigation
https://www.readbyqxmd.com/read/28212332/type-1-diabetes-candidate-genes-linked-to-pancreatic-islet-cell-inflammation-and-beta-cell-apoptosis
#3
REVIEW
Joachim Størling, Flemming Pociot
Type 1 diabetes (T1D) is a chronic immune-mediated disease resulting from the selective destruction of the insulin-producing pancreatic islet β-cells. Susceptibility to the disease is the result of complex interactions between environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified more than 50 genetic regions that affect the risk of developing T1D. Most of these susceptibility loci, however, harbor several genes, and the causal variant(s) and gene(s) for most of the loci remain to be established...
February 16, 2017: Genes
https://www.readbyqxmd.com/read/28210075/pancreatic-stellate-cell-pandora-s-box-for-pancreatic-disease-biology
#4
REVIEW
Ratnakar R Bynigeri, Aparna Jakkampudi, Ramaiah Jangala, Chivukula Subramanyam, Mitnala Sasikala, G Venkat Rao, D Nageshwar Reddy, Rupjyoti Talukdar
Pancreatic stellate cells (PSCs) were identified in the early 1980s, but received much attention after 1998 when the methods to isolate and culture them from murine and human sources were developed. PSCs contribute to a small proportion of all pancreatic cells under physiological condition, but are essential for maintaining the normal pancreatic architecture. Quiescent PSCs are characterized by the presence of vitamin A laden lipid droplets. Upon PSC activation, these perinuclear lipid droplets disappear from the cytosol, attain a myofibroblast like phenotype and expresses the activation marker, alpha smooth muscle actin...
January 21, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28208933/a-rare-case-report-of-hepatic-subcapsular-pseudocyst-of-pancreas
#5
Noor Topno, Sandeep Ghosh, Arup Baruah
A pancreatic pseudocyst arises as a result of acute or chronic pancreatitis, pancreatic trauma, or obstruction of the pancreatic duct by a neoplasm. Most of the pseudocysts are located within the head and the body of the pancreas but 20% are extra-pancreatic. We report a case of a 33-year-old gentleman presenting with acute on chronic alcoholic pancreatitis with hepatic sub-capsular pseudocyst involving left lobe of liver, with intra-cystic bleed was successfully treated with Ultrasonography (USG) guided drainage...
December 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28208230/emerging-role-of-gsk-3%C3%AE-in-the-pathobiology-of-classical-hodgkin-lymphoma
#6
Claudio Agostinelli, Silvia Carloni, Francesco Limarzi, Simona Righi, Maria Antonella Laginestra, Gerardo Musuraca, Michelangelo Fiorentino, Roberta Napolitano, Antonio Cuneo, Daniele Vergara, Pier Luigi Zinzani, Sabattini Elena, Stefano A Pileri, Serena De Matteis
AIMS: GSK-3β is a serine/threonine kinase involved in glycogen metabolism, cell cycle progression, differentiation, embryogenesis, migration, metabolism, survival and cellular senescence. Its main biological function is to inhibit β-catenin by sequestration and promotion of its proteasomal degradation in the Wnt canonical pathway, however GSK-3β interacts with multiple signaling pathways and aberrant expression of the enzyme was reported in many solid neoplasms. This study aimed to investigate the biological relevance of GSK-3β in classical Hodgkin Lymphomas (cHL)...
February 16, 2017: Histopathology
https://www.readbyqxmd.com/read/28207747/chronic-pancreatitis-multicentre-prospective-data-collection-and-analysis-by-the-hungarian-pancreatic-study-group
#7
Ákos Szücs, Tamás Marjai, Andrea Szentesi, Nelli Farkas, Andrea Párniczky, György Nagy, Balázs Kui, Tamás Takács, László Czakó, Zoltán Szepes, Balázs Csaba Németh, Áron Vincze, Gabriella Pár, Imre Szabó, Patrícia Sarlós, Anita Illés, Szilárd Gódi, Ferenc Izbéki, Judit Gervain, Adrienn Halász, Gyula Farkas, László Leindler, Dezső Kelemen, Róbert Papp, Richárd Szmola, Márta Varga, József Hamvas, János Novák, Barnabás Bod, Miklós Sahin-Tóth, Péter Hegyi
INTRODUCTION: Chronic pancreatitis is an inflammatory disease associated with structural and functional damage to the pancreas, causing pain, maldigestion and weight loss and thus worsening the quality of life. AIMS AND METHODS: Our aim was to find correlations from a multicentre database representing the epidemiological traits, diagnosis and treatment of the disease in Hungary. The Hungarian Pancreatic Study Group collected data prospectively from 2012 to 2014 on patients suffering from chronic pancreatitis...
2017: PloS One
https://www.readbyqxmd.com/read/28207725/ethnic-and-geographic-variations-in-the-incidence-of-pancreatitis-and-post-pancreatitis-diabetes-mellitus-in-new-zealand-a-nationwide-population-based-study
#8
Sayali A Pendharkar, Juby Mathew, Jinfeng Zhao, John A Windsor, Daniel J Exeter, Maxim S Petrov
AIM: To determine the incidence of acute pancreatitis (AP), chronic pancreatitis (CP), and post-pancreatitis diabetes mellitus (DP) in New Zealand, and the effect of ethnic and geographic variations. METHODS: Data were collected from all district health boards in New Zealand by the Ministry of Health (Manatū Hauora). Diagnosis of AP, CP and DP was determined by the International Classification of Diseases-10 codes. Incidence rates per 100,000 population per year were calculated using incident AP, CP and DP cases as the numerator, and the adult resident population of New Zealand as the denominator...
February 17, 2017: New Zealand Medical Journal
https://www.readbyqxmd.com/read/28203472/cyanoacrylate-associated-foreign-body-granulomatous-gastritis-a-report-of-three-cases
#9
Gunes Guner, Olcay Kurtulan, Taylan Kav, Cenk Sokmensuer, Gokhan Gedikoglu, Aytekin Akyol
Granulomas are rarely seen in gastric biopsies mostly as an involvement of granulomatous diseases like sarcoidosis, Crohn's disease, infections, neoplasms, and vasculitis. Here, we claim cyanoacrylate as a foreign body type granuloma-causing agent in the stomach after vascular embolisation. We present cyanoacrylate associated gastric changes of three cases: two endoscopic biopsies and one gastric resection. In two cases, cyanoacrylate associated ulcers and granulomatous inflammation were observed in gastric mucosal biopsies following endoscopic examination after 7 months and 6 years of the glue injections, respectively...
2017: Case Reports in Pathology
https://www.readbyqxmd.com/read/28202581/identification-and-functional-implications-of-sodium-myo-inositol-cotransporter-1-in-pancreatic-beta-cells-and-type-2-diabetes-mellitus
#10
Stephen Yu Ting Li, Sam Tsz Wai Cheng, Dan Zhang, Po Sing Leung
Myo-inositol (MI), the precursor of the second messenger phosphoinositide (PI), mediates multiple cellular events. Rat islets exhibit active transport of MI, though the mechanism involved remains elusive. Here, we report, for the first time, the expression of sodium/myo-inositol cotransporter 1 (SMIT1) in rat islets and specifically, β-cells. Genetic or pharmacological inhibition of SMIT impaired glucose-stimulated insulin secretion by INS-1E cells, probably via down-regulation of PI signaling. Additionally, we found that SMIT1 expression in INS-1E cells and isolated islets was augmented by acute high-glucose exposure and reduced in chronic hyperglycemia conditions...
February 15, 2017: Diabetes
https://www.readbyqxmd.com/read/28202235/stx12-lncrna-mir-148a-smad5-participate-in-the-regulation-of-pancreatic-stellate-cell-activation-through-a-mechanism-involving-competing-endogenous-rna
#11
Hao Wang, Yanfeng Jiang, Ming Lu, Bei Sun, Xin Qiao, Dongbo Xue, Weihui Zhang
BACKGROUND: With the deepening of research, the roles of LncRNAs play in the fibrotic process have attracted great attention. At the early stage of pancreatic fibrogenesis, to effectively regulate pancreatic stellate cells (PSCs) activation is crucial for the treatment of chronic pancreatic fibrosis. METHODS: Microarray data on chronic pancreatitis were retrieved from the Gene Expression Omnibus (GEO) repository and analyzed using bioinformatic methods. A diagram of the lncRNA-miRNA-mRNA ceRNA network was constructed...
February 1, 2017: Pancreatology: Official Journal of the International Association of Pancreatology (IAP) ... [et Al.]
https://www.readbyqxmd.com/read/28202062/isolated-igg4-related-sclerosing-cholangitis-misdiagnosed-as-malignancy-in-an-area-with-endemic-cholangiocarcinoma-a-case-report
#12
Narongsak Rungsakulkij, Pattana Sornmayura, Penampai Tannaphai
BACKGROUND: The most common cause of perihilar obstruction is cholangiocarcinoma, especially in Thailand. Benign perihilar stricture represents less than 20% of cases. IgG4-related disease and IgG4-related sclerosing cholangitis, however, have been receiving increased recognition. Isolated IgG4-related sclerosing cholangitis is less common. The preoperative diagnosis of IgG4-related sclerosing cholangitis without pancreatic involvement is very difficult because the clinical presentation and preoperative evaluation are extremely difficult to distinguish from perihilar cholangiocarcinoma...
February 15, 2017: BMC Surgery
https://www.readbyqxmd.com/read/28201840/clinical-response-to-dorsal-duct-drainage-via-the-minor-papilla-in-refractory-obstructing-chronic-calcific-pancreatitis
#13
Chang-Il Kwon, Mark A Gromski, Stuart Sherman, Ihab I El Hajj, Jeffrey J Easler, James Watkins, Lee McHenry, Glen A Lehman, Evan L Fogel
Background and study aims Complete stone removal from the main pancreatic duct might not be achieved in all patients with obstructive chronic calcific pancreatitis. We report our results for endoscopic dorsal pancreatic duct (DPD) bypass of obstructing stones in the ventral pancreatic duct (VPD). Patients and methods 16 patients with obstructive chronic calcific pancreatitis were treated with a DPD bypass. Clinical success was defined as significant pain relief and no hospital admissions for pain management during the ongoing treatment period...
February 15, 2017: Endoscopy
https://www.readbyqxmd.com/read/28198796/carbonic-anhydrase-i-and-ii-autoantibodies-in-beh%C3%A3-et-s-disease
#14
Ahmet Mentese, Ahmet Alver, Selim Demir, Aysegul Sumer, Serap Ozer Yaman, Murat Karkucak, Arzu Aydin Capkin, Diler Us Altay, Ibrahim Turan
BACKGROUND: Behçet's disease is a vasculitis, seen more frequently around the Mediterranean and the Far East, and evinces with oral and genital ulcerations, skin lesions and uveitis. Carbonic anhydrase (CA) is a metalloenzyme which is widely distributed in the living world, and it is essential for the regulation of acid-base balance. Anti-CA antibodies have been reported in many disorders, such as systemic lupus erythematosus, Sjögren's syndrome, rheumatoid arthritis, endometriosis, idiopathic chronic pancreatitis, type 1 diabetes and Graves' disease...
December 3, 2016: Acta Reumatológica Portuguesa
https://www.readbyqxmd.com/read/28197985/inonotus-obliquus-polysaccharide-regulates-gut-microbiota-of-chronic-pancreatitis-in-mice
#15
Yang Hu, Chunying Teng, Sumei Yu, Xin Wang, Jinsong Liang, Xin Bai, Liying Dong, Tao Song, Min Yu, Juanjuan Qu
Polysaccharide is efficient in attenuation of metabolic ailments and modulation of gut microbiota as prebiotics. The therapeutic effect of Inonotus obliquus polysaccharide (IOP) on chronic pancreatitis (CP) in mice has been validated in our previous study. However, it is not clear whether IOP is conducive to maintaining the homeostasis between gut microbiota and host. The aim of this study is to testify the potential effects of IOP on gut microbiota composition and diversity in mice with CP. The changes in glutathione peroxidase (GSH-PX), total antioxidant capacity (TAOC), tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), lipase and trypsin levels were measured by commercial assay kits, meanwhile the gut microbiota composition and diversity were analyzed by high throughput sequencing...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28197316/design-and-synthesis-of-novel-selective-gpr40-agopams
#16
Christopher W Plummer, Matthew J Clements, Helen Chen, Murali Rajagopalan, Hubert Josien, William K Hagmann, Michael Miller, Maria E Trujillo, Melissa Kirkland, Daniel Kosinski, Joel Mane, Michele Pachanski, Boonlert Cheewatrakoolpong, Andrew F Nolting, Robert Orr, Melodie Christensen, Louis-Charles Campeau, Michael J Wright, Randal Bugianesi, Sarah Souza, Xiaoping Zhang, Jerry Di Salvo, Adam B Weinglass, Richard Tschirret-Guth, Ravi Nargund, Andrew D Howard, Steven L Colletti
GPR40 is a G-protein-coupled receptor expressed primarily in pancreatic islets and intestinal L-cells that has been a target of significant recent therapeutic interest for type II diabetes. Activation of GPR40 by partial agonists elicits insulin secretion only in the presence of elevated blood glucose levels, minimizing the risk of hypoglycemia. GPR40 agoPAMs have shown superior efficacy to partial agonists as assessed in a glucose tolerability test (GTT). Herein, we report the discovery and optimization of a series of potent, selective GPR40 agoPAMs...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28197205/from-pathogenesis-clinical-manifestation-and-diagnosis-to-treatment-an-overview-on-autoimmune-pancreatitis
#17
REVIEW
Ou Cai, Shiyun Tan
Autoimmune pancreatitis (AIP) is a special type of chronic pancreatitis which is autoimmune mediated. The international consensus diagnostic criteria (ICDC) 2011 proposed two types of AIP: type I is associated with histological pattern of lymphoplasmacytic sclerosing pancreatitis (LPSP), characterized by serum IgG4 elevation, whereas type 2 is named idiopathic duct-centric pancreatitis (IDCP), with granulocytic epithelial lesion (GEL) and immunoglobulin G4 (IgG4) negative. The pathogenic mechanism is unclear now; based on genetic factors, disease specific or related antigens, innate and adaptive immunity may be involved...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28196021/the-changing-epidemiology-of-acute-pancreatitis-hospitalizations-a-decade-of-trends-and-the-impact-of-chronic-pancreatitis
#18
Somashekar G Krishna, Amrit K Kamboj, Phil A Hart, Alice Hinton, Darwin L Conwell
OBJECTIVES: The epidemiological trends contributing to increasing acute pancreatitis (AP) hospitalizations remain unknown. We sought to analyze etiological factors and outcomes of increasing AP hospitalizations. METHODS: Utilizing the Nationwide Inpatient Sample, retrospective analyses of adult (≥18 years) inpatient admissions with a primary diagnosis of AP (N = 2,016,045) were performed. Patient hospitalizations from 2009 to 2012 were compared with those from 2002 to 2005...
February 14, 2017: Pancreas
https://www.readbyqxmd.com/read/28196019/pancreatoscopy-directed-electrohydraulic-lithotripsy-for-pancreatic-ductal-stones-in-painful-chronic-pancreatitis-using-spyglass
#19
Noor L H Bekkali, Sam Murray, Gavin J Johnson, Steven Bandula, Zahir Amin, Michael H Chapman, Stephen P Pereira, George J M Webster
OBJECTIVE: Painful chronic pancreatitis is often associated with main duct obstruction due to stones. Approaches to management are challenging, including surgery, extracorporeal shock wave lithotripsy, or endoscopic approaches. Here, we report our experience of pancreatoscopy + electrohydraulic lithotripsy (EHL) for pancreatic duct (PD) stones using SpyGlass. METHODS: We retrospectively audited the use of SpyGlass (Legacy and DS) + EHL. Indication, procedural details, and clinical outcomes were assessed...
February 14, 2017: Pancreas
https://www.readbyqxmd.com/read/28196017/endoscopic-ultrasonography-may-select-subjects-having-asymptomatic-chronic-pancreatic-hyperenzymemia-who-require-a-more-strict-follow-up
#20
Filippo Antonini, Valerio Belfiori, Nico Pagano, Elisabetta Buscarini, Samuele De Minicis, Massimiliano Lo Cascio, Barbara Marraccini, Simona Piergallini, Pamela Rossetti, Elena Andrenacci, Giampiero Macarri, Raffaele Pezzilli
OBJECTIVES: We have previously shown that at least 50% of patients having asymptomatic chronic pancreatic hyperenzymemia (ACPH) may develop morphological pancreatic alterations. Endoscopic ultrasonography (EUS) may detect small lesions, and its sensitivity seems to be higher than other imaging techniques. The aim of this study was to evaluate whether EUS may modify the management of patients having ACPH. METHODS: In 2 referral centers for pancreatic disease, a retrospective analysis of prospectively enrolled patients with ACPH was conducted...
February 14, 2017: Pancreas
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