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Sample records for cerulein-stimulated pancreatic acinar

  1. Papillocystic Variant of Acinar Cell Pancreatic Carcinoma

    Directory of Open Access Journals (Sweden)

    Jasim Radhi

    2010-01-01

    Full Text Available Acinar cell pancreatic carcinoma is a rare solid malignant neoplasm. Recent review of the literature showed occasional cases with papillary or papillocystic growth patterns, ranging from 2 to 5 cm in diameter. We report a large 10 cm pancreatic tumor with papillocystic pathology features involving the pancreatic head. The growth pattern of these tumors could be mistaken for intraductal papillary mucinous tumors or other pancreatic cystic neoplasms.

  2. Inflammatory role of the acinar cells during acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Isabel; De; Dios

    2010-01-01

    Pancreatic acinar cells are secretory cells whose main function is to synthesize, store and f inally release digestive enzymes into the duodenum. However, in response to noxious stimuli, acinar cells behave like real inflammatory cells because of their ability to activate signalling transduction pathways involved in the expression of inflammatory mediators. Mediated by the kinase cascade, activation of Nuclear factor-κB, Activating factor-1 and Signal transducers and activators of transcription transcription factors has been demonstrated in acinar cells, resulting in overexpression of inflammatory genes. In turn, kinase activity is down-regulated by protein phosphatases and the f inal balance between kinase and phosphatase activity will determine the capability of the acinar cells to produce inflammatory factors. The kinase/ phosphatase pair is a redox-sensitive system in which kinase activation overwhelms phosphatase activity under oxidant conditions. Thus, the oxidative stress developed within acinar cells at early stages of acute pancreatitis triggers the activation of signalling pathways involved in the up-regulation of cytokines, chemokines and adhesion molecules. In this way, acinar cells trigger the release of the f irst inflammatory signals which can mediate the activation and recruitment of circulating inflammatorycells into the injured pancreas. Accordingly, the role of acinar cells as promoters of the inflammatory response in acute pancreatitis may be considered. This concept leads to amplifying the focus from leukocyte to acinar cells themselves, to explain the local inflammation in early pancreatitis.

  3. Recurrent Pancreatitis Due to a Cystic Pancreatic Tumor: A Rare Presentation of Acinar Cell Carcinoma

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    Raimondo M

    2004-05-01

    Full Text Available CONTEXT: Acinar cell carcinoma is an uncommon malignancy of the pancreas. It has characteristic histomorphology, immunohistochemistry profile, and clinicopathological behavior. CASE REPORT: We report a rare case of recurrent pancreatitis secondary to acinar cell carcinoma of the pancreas. We describe the endoscopic ultrasound characteristic, treatment and the surgical outcome. CONCLUSIONS: Acinar cell carcinoma should be considered in the differential diagnosis of cystic pancreatic tumors presenting with recurrent pancreatitis.

  4. Recurrent Pancreatitis Due to a Cystic Pancreatic Tumor: A Rare Presentation of Acinar Cell Carcinoma

    OpenAIRE

    Raimondo M; Krishna M; Nguyen J; Scolapio J; Aqel B

    2004-01-01

    CONTEXT: Acinar cell carcinoma is an uncommon malignancy of the pancreas. It has characteristic histomorphology, immunohistochemistry profile, and clinicopathological behavior. CASE REPORT: We report a rare case of recurrent pancreatitis secondary to acinar cell carcinoma of the pancreas. We describe the endoscopic ultrasound characteristic, treatment and the surgical outcome. CONCLUSIONS: Acinar cell carcinoma should be considered in the differential diagnosis of cystic pancreatic tumors pre...

  5. File list: DNS.Pan.20.AllAg.Pancreatic_acinar_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available DNS.Pan.20.AllAg.Pancreatic_acinar_cells mm9 DNase-seq Pancreas Pancreatic acinar c...ells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/DNS.Pan.20.AllAg.Pancreatic_acinar_cells.bed ...

  6. File list: ALL.Pan.05.AllAg.Pancreatic_acinar_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  7. File list: Oth.Pan.05.AllAg.Pancreatic_acinar_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Oth.Pan.05.AllAg.Pancreatic_acinar_cells mm9 TFs and others Pancreas Pancreatic aci...nar cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Oth.Pan.05.AllAg.Pancreatic_acinar_cells.bed ...

  8. File list: ALL.Pan.50.AllAg.Pancreatic_acinar_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available ALL.Pan.50.AllAg.Pancreatic_acinar_cells mm9 All antigens Pancreas Pancreatic acina...r cells SRX327161,SRX327160,SRX327162,SRX327163 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/ALL.Pan.50.AllAg.Pancreatic_acinar_cells.bed ...

  9. File list: Pol.Pan.50.AllAg.Pancreatic_acinar_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Pan.50.AllAg.Pancreatic_acinar_cells mm9 RNA polymerase Pancreas Pancreatic aci...nar cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Pan.50.AllAg.Pancreatic_acinar_cells.bed ...

  10. File list: Pol.Pan.10.AllAg.Pancreatic_acinar_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available Pol.Pan.10.AllAg.Pancreatic_acinar_cells mm9 RNA polymerase Pancreas Pancreatic aci...nar cells http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/Pol.Pan.10.AllAg.Pancreatic_acinar_cells.bed ...

  11. Ca2+ signaling in pancreatic acinar cells: physiology and pathophysiology

    Directory of Open Access Journals (Sweden)

    O.H. Petersen

    2009-01-01

    Full Text Available The pancreatic acinar cell is a classical model for studies of secretion and signal transduction mechanisms. Because of the extensive endoplasmic reticulum and the large granular compartment, it has been possible - by direct measurements - to obtain considerable insights into intracellular Ca2+ handling under both normal and pathological conditions. Recent studies have also revealed important characteristics of stimulus-secretion coupling mechanisms in isolated human pancreatic acinar cells. The acinar cells are potentially dangerous because of the high intra-granular concentration of proteases, which become inappropriately activated in the human disease acute pancreatitis. This disease is due to toxic Ca2+ signals generated by excessive liberation of Ca2+ from both the endoplasmic reticulum and the secretory granules.

  12. Pancreatic ductal bicarbonate secretion: challenge of the acinar acid load

    Directory of Open Access Journals (Sweden)

    Peter eHegyi

    2011-07-01

    Full Text Available Acinar and ductal cells of the exocrine pancreas form a close functional unit. Although most studies contain data either on acinar or ductal cells, an increasing number of evidence highlights the importance of the pancreatic acinar-ductal functional unit. One of the best examples for this functional unit is the regulation of luminal pH by both cell types. Protons co-released during exocytosis from acini cause significant acidosis, whereas, bicarbonate secreted by ductal cells cause alkalization in the lumen. This suggests that the first and probably one of the most important role of bicarbonate secretion by pancreatic ductal cells is not only to neutralize the acid chyme entering into the duodenum from the stomach, but to neutralize acidic content secreted by acinar cells. To accomplish this role, it is more than likely that ductal cells have physiological sensing mechanisms which would allow them to regulate luminal pH. To date, four different classes of acid-sensing ion channels have been identified in the gastrointestinal tract (transient receptor potential ion channels, two-pore domain potassium channel, ionotropic purinoceptor and acid-sensing ion channel, however, none of these have been studied in pancreatic ductal cells. In this mini-review, we summarize our current knowledge of these channels and urge scientists to characterize ductal acid-sensing mechanisms and also to investigate the challenge of the acinar acid load on ductal cells.

  13. TGF-β1 promotes acinar to ductal metaplasia of human pancreatic acinar cells.

    Science.gov (United States)

    Liu, Jun; Akanuma, Naoki; Liu, Chengyang; Naji, Ali; Halff, Glenn A; Washburn, William K; Sun, Luzhe; Wang, Pei

    2016-01-01

    Animal studies suggest that pancreatitis-induced acinar-to-ductal metaplasia (ADM) is a key event for pancreatic ductal adenocarcinoma (PDAC) initiation. However, there has not been an adequate system to explore the mechanisms of human ADM induction. We have developed a flow cytometry-based, high resolution lineage tracing method and 3D culture system to analyse ADM in human cells. In this system, well-known mouse ADM inducers did not promote ADM in human cells. In contrast, TGF-β1 efficiently converted human acinar cells to duct-like cells (AD) in a SMAD-dependent manner, highlighting fundamental differences between the species. Functionally, AD cells gained transient proliferative capacity. Furthermore, oncogenic KRAS did not induce acinar cell proliferation, but did sustain the proliferation of AD cells, suggesting that oncogenic KRAS requires ADM-associated-changes to promote PDAC initiation. This ADM model provides a novel platform to explore the mechanisms involved in the development of human pancreatic diseases. PMID:27485764

  14. KRAS Mutations in Canine and Feline Pancreatic Acinar Cell Carcinoma.

    Science.gov (United States)

    Crozier, C; Wood, G A; Foster, R A; Stasi, S; Liu, J H W; Bartlett, J M S; Coomber, B L; Sabine, V S

    2016-07-01

    Companion animals may serve as valuable models for studying human cancers. Although KRAS is the most commonly mutated gene in human ductal pancreatic cancers (57%), with mutations frequently occurring at codons 12, 13 and 61, human pancreatic acinar cell carcinomas (ACCs) lack activating KRAS mutations. In the present study, 32 pancreatic ACC samples obtained from 14 dogs and 18 cats, including seven metastases, were analyzed for six common activating KRAS mutations located in codons 12 (n = 5) and 13 (n = 1) using Sequenom MassARRAY. No KRAS mutations were found, suggesting that, similar to human pancreatic ACC, KRAS mutations do not play a critical role in feline or canine pancreatic ACC. Due to the similarity of the clinical disease in dogs and cats to that of man, this study confirms that companion animals offer potential as a suitable model for investigating this rare subtype of pancreatic carcinoma. PMID:27290644

  15. Alteration of chaperonin60 and pancreatic enzyme in pancreatic acinar cell under pathological condition

    Institute of Scientific and Technical Information of China (English)

    Yong-Yu Li; Moise Bendayan

    2005-01-01

    AIM: To investigate the changes of chaperonin60 (Cpn60)and pancreatic enzymes in pancreatic acinar cells, and to explore their roles in the development of experimental diabetes and acute pancreatitis (AP).METHODS: Two different pathological models were replicated in Sprague-Dawley rats: streptozotocininduced diabetes and sodium deoxycholate-induced AP. The contents of Cpn60 and pancreatic enzymes in different compartments of the acinar cells were measured by quantitative immunocytochemistry.RESULTS: The levels of Cpn60 significantly increased in diabetes, but decreased in AP, especially in the zymogen granules of the pancreatic acinar cells. The elevation of Cpn60 was accompanied with the increased levels of pancreatic lipase and chymotrypsinogen in diabetes.However, a decreased Cpn60 level was accompanied by high levels of lipase and chymotrypsinogen in AP.The amylase level was markedly reduced in both the pathological conditions.CONCLUSION: The equilibrium between Cpn60 and pancreatic enzymes in the acinar cells breaks in AP, and Cpn60 content decreases, suggesting an insufficient chaperone capacity. This may promote the aggregation and autoactivation of the premature enzymes in the pancreatic acinar cells and play roles in the development of AP.

  16. Effect of Taurine on Acinar Cell Apoptosis and Pancreatic Fibrosis in Dibutyltin Dichloride-induced Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Sawa,Kiminari

    2012-08-01

    Full Text Available The relationship between pancreatic fibrosis and apoptosis of pancreatic acinar cells has not been fully elucidated. We reported that taurine had an anti-fibrotic effect in a dibutyltin dichloride (DBTC-chronic pancreatitis model. However, the effect of taurine on apoptosis of pancreatic acinar cells is still unclear. Therefore, we examined apoptosis in DBTC-chronic pancreatitis and in the AR42J pancreatic acinar cell line with/without taurine. Pancreatic fibrosis was induced by a single administration of DBTC. Rats were fed a taurine-containing diet or a normal diet and were sacrificed at day 5. The AR42J pancreatic acinar cell line was incubated with/without DBTC with taurine chloramines. Apoptosis was determined by using terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL assay. The expression of Bad and Bcl-2 proteins in the AR42J cells lysates was detected by Western blot analysis. The apoptotic index of pancreatic acinar cells in DBTC-administered rats was significantly increased. Taurine treatment inhibited pancreatic fibrosis and apoptosis of acinar cells induced by DBTC. The number of TUNEL-positive cells in the AR42J pancreatic acinar cell lines was significantly increased by the addition of DBTC. Incubation with taurine chloramines ameliorated these changes. In conclusion, taurine inhibits apoptosis of pancreatic acinar cells and pancreatitis in experimental chronic pancreatitis.

  17. Pancreatic acinar cells-derived cyclophilin A promotes pancreatic damage by activating NF-κB pathway in experimental pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Ge [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Wan, Rong [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Hu, Yanling [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Ni, Jianbo [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Yin, Guojian; Xing, Miao [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Shen, Jie [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Tang, Maochun [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Chen, Congying [Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); Fan, Yuting; Xiao, Wenqin; Zhao, Yan [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Wang, Xingpeng, E-mail: wangxingpeng@hotmail.com [Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai (China); Department of Gastroenterology, Shanghai First People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai (China); and others

    2014-01-31

    Highlights: • CypA is upregulated in experimental pancreatitis. • CCK induces expression and release of CypA in acinar cell in vitro. • rCypA aggravates CCK-induced acinar cell death and inflammatory cytokine production. • rCypA activates the NF-κB pathway in acinar cells in vitro. - Abstract: Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration of sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-κB p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-κB pathway.

  18. Pancreatic acinar cells-derived cyclophilin A promotes pancreatic damage by activating NF-κB pathway in experimental pancreatitis

    International Nuclear Information System (INIS)

    Highlights: • CypA is upregulated in experimental pancreatitis. • CCK induces expression and release of CypA in acinar cell in vitro. • rCypA aggravates CCK-induced acinar cell death and inflammatory cytokine production. • rCypA activates the NF-κB pathway in acinar cells in vitro. - Abstract: Inflammation triggered by necrotic acinar cells contributes to the pathophysiology of acute pancreatitis (AP), but its precise mechanism remains unclear. Recent studies have shown that Cyclophilin A (CypA) released from necrotic cells is involved in the pathogenesis of several inflammatory diseases. We therefore investigated the role of CypA in experimental AP induced by administration of sodium taurocholate (STC). CypA was markedly upregulated and widely expressed in disrupted acinar cells, infiltrated inflammatory cells, and tubular complexes. In vitro, it was released from damaged acinar cells by cholecystokinin (CCK) induction. rCypA (recombinant CypA) aggravated CCK-induced acinar cell necrosis, promoted nuclear factor (NF)-κB p65 activation, and increased cytokine production. In conclusion, CypA promotes pancreatic damage by upregulating expression of inflammatory cytokines of acinar cells via the NF-κB pathway

  19. THE CHANGES OF PANCREATIC ACINAR CELL FUNCTION IN ACUTE NECROTIZING PANCREATITIS OF RATS

    Institute of Scientific and Technical Information of China (English)

    余枭; 韩天权; 汤耀卿; 雷若庆; 夏宗勤

    2000-01-01

    Objective To evaluate the changes of pancreatic acinar cell functions in the rats with acute necrotizing pancreatitis (ANP). Methods Seventy SD rats were randomized into two groups: experimental group (n=35) and control group (n=35). To prepare the experimental model, the retrograde injection of 5% sodium taurocholate into the pancreatic duct was used for inducing ANP. Radioactive tracing by L- 3H-phenylalanine and autoradiography were performed for scoring the differences of changes of amino acid uptake, enzyme-protein synthesis and output from acinar cells in rats between both groups. Results No changes were observed in amino acid uptake and enzyme-protein synthesis in rats with dotted and haemorrhagic necrotizing foci as compared with control group. However, accumulated zymogen granules in the interstitial of acinar cells were seen in the experimental group. Conclusion It indicates that in experimental ANP rats, the functions of acinar cells in both amino acid uptake and protein synthesis were essentially normal, but the pathway of enzyme output was affected into ectopic secretion through the bottom or lateral cellular membrane of pancreatic acinar cell.

  20. File list: NoD.Pan.20.AllAg.Pancreatic_acinar_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: InP.Pan.10.AllAg.Pancreatic_acinar_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Pan.10.AllAg.Pancreatic_acinar_cells mm9 Input control Pancreas Pancreatic acin...ar cells SRX327162,SRX327163 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Pan.10.AllAg.Pancreatic_acinar_cells.bed ...

  2. File list: InP.Pan.50.AllAg.Pancreatic_acinar_cells [Chip-atlas[Archive

    Lifescience Database Archive (English)

    Full Text Available InP.Pan.50.AllAg.Pancreatic_acinar_cells mm9 Input control Pancreas Pancreatic acin...ar cells SRX327162,SRX327163 http://dbarchive.biosciencedbc.jp/kyushu-u/mm9/assembled/InP.Pan.50.AllAg.Pancreatic_acinar_cells.bed ...

  3. Calcium signaling of pancreatic acinar cells in the pathogenesis of pancreatitis.

    Science.gov (United States)

    Li, Jun; Zhou, Rui; Zhang, Jian; Li, Zong-Fang

    2014-11-21

    Pancreatitis is an increasingly common and sometimes severe disease that lacks a specific therapy. The pathogenesis of pancreatitis is still not well understood. Calcium (Ca(2+)) is a versatile carrier of signals regulating many aspects of cellular activity and plays a central role in controlling digestive enzyme secretion in pancreatic acinar cells. Ca(2+) overload is a key early event and is crucial in the pathogenesis of many diseases. In pancreatic acinar cells, pathological Ca(2+) signaling (stimulated by bile, alcohol metabolites and other causes) is a key contributor to the initiation of cell injury due to prolonged and global Ca(2+) elevation that results in trypsin activation, vacuolization and necrosis, all of which are crucial in the development of pancreatitis. Increased release of Ca(2+) from stores in the intracellular endoplasmic reticulum and/or increased Ca(2+) entry through the plasma membrane are causes of such cell damage. Failed mitochondrial adenosine triphosphate (ATP) production reduces re-uptake and extrusion of Ca(2+) by the sarco/endoplasmic reticulum Ca(2+)-activated ATPase and plasma membrane Ca(2+)-ATPase pumps, which contribute to Ca(2+) overload. Current findings have provided further insight into the roles and mechanisms of abnormal pancreatic acinar Ca(2+) signals in pancreatitis. The lack of available specific treatments is therefore an objective of ongoing research. Research is currently underway to establish the mechanisms and interactions of Ca(2+) signals in the pathogenesis of pancreatitis.

  4. Nicotine as a mitogenic stimulus for pancreatic acinar cell proliferation

    Institute of Scientific and Technical Information of China (English)

    Parimal Chowdhury; Kodetthoor B Udupa

    2006-01-01

    Cell proliferation is an important process in life for growth of normal and cancer cells. The signal transduction pathways activated during this process are strictly regulated. This editorial focuses on the role of nicotine,a mitogen, in the induction of signaling pathways resulting in proliferation of pancreatic tumor cells and compares these events with those in normal acinar cells isolated from the rat pancreas. The data shows striking similarities between these two cellular systems.In addition, the editorial reviews very recent literature of the contribution of MAPK signaling in cell lines associated with human diseases. A prospective cellular model of nicotine induced activation of MAPK cascade is presented.

  5. Functional somatostatin receptors on a rat pancreatic acinar cell line

    International Nuclear Information System (INIS)

    Somatostatin receptors from a rat pancreatic acinar cell line, AR4-2J, were characterized biochemically, structurally, and functionally. Binding of 125I-[Tyr11]Somatostatin to AR4-2J cells was saturable, exhibiting a single class of high-affinity binding sites with a maximal binding capacity of 258 ± 20 fmol/106 cells. Somatostatin receptor structure was analyzed by covalently cross-linking 125I-[Tyr11]somatostatin to its plasma membrane receptors. Gel electrophoresis and autoradiography of cross-linked proteins revealed a peptide containing the somatostatin receptor. Somatostatin inhibited vasoactive intestinal peptide (VIP)-stimulated adenosine 3',5'-cyclic monophosphate (cAMP) formation in a dose-dependent manner. The concentration of somatostatin that caused half-maximal inhibition of cAMP formation was close to the receptor affinity for somatostatin. Pertussis toxin pretreatment of AR4-2J cells prevented somatostatin inhibition of VIP-stimulated cAMP formation as well as somatostatin binding. The authors conclude that AR4-2J cells exhibit functional somatostatin receptors that retain both specificity and affinity of the pancreatic acinar cell somatostatin receptors and act via the pertussis toxin-sensitive guanine nucleotide-binding protein Ni to inhibit adenylate cyclase

  6. Serotonin promotes acinar dedifferentiation following pancreatitis-induced regeneration in the adult pancreas.

    Science.gov (United States)

    Saponara, Enrica; Grabliauskaite, Kamile; Bombardo, Marta; Buzzi, Raphael; Silva, Alberto B; Malagola, Ermanno; Tian, Yinghua; Hehl, Adrian B; Schraner, Elisabeth M; Seleznik, Gitta M; Zabel, Anja; Reding, Theresia; Sonda, Sabrina; Graf, Rolf

    2015-12-01

    The exocrine pancreas exhibits a distinctive capacity for tissue regeneration and renewal following injury. This regenerative ability has important implications for a variety of disorders, including pancreatitis and pancreatic cancer, diseases associated with high morbidity and mortality. Thus, understanding its underlying mechanisms may help in developing therapeutic interventions. Serotonin has been recognized as a potent mitogen for a variety of cells and tissues. Here we investigated whether serotonin exerts a mitogenic effect in pancreatic acinar cells in three regenerative models, inflammatory tissue injury following pancreatitis, tissue loss following partial pancreatectomy, and thyroid hormone-stimulated acinar proliferation. Genetic and pharmacological techniques were used to modulate serotonin levels in vivo. Acinar dedifferentiation and cell cycle progression during the regenerative phase were investigated over the course of 2 weeks. By comparing acinar proliferation in the different murine models of regeneration, we found that serotonin did not affect the clonal regeneration of mature acinar cells. Serotonin was, however, required for acinar dedifferentiation following inflammation-mediated tissue injury. Specifically, lack of serotonin resulted in delayed up-regulation of progenitor genes and delayed the formation of acinar-to-ductal metaplasia and defective acinar cell proliferation. We identified serotonin-dependent acinar secretion as a key step in progenitor-based regeneration, as it promoted acinar cell dedifferentiation and the recruitment of type 2 macrophages. Finally, we identified a regulatory Hes1-Ptfa axis in the uninjured adult pancreas, activated by zymogen secretion. Our findings indicated that serotonin plays a critical role in the regeneration of the adult pancreas following pancreatitis by promoting the dedifferentiation of acinar cells.

  7. Serotonin promotes acinar dedifferentiation following pancreatitis-induced regeneration in the adult pancreas.

    Science.gov (United States)

    Saponara, Enrica; Grabliauskaite, Kamile; Bombardo, Marta; Buzzi, Raphael; Silva, Alberto B; Malagola, Ermanno; Tian, Yinghua; Hehl, Adrian B; Schraner, Elisabeth M; Seleznik, Gitta M; Zabel, Anja; Reding, Theresia; Sonda, Sabrina; Graf, Rolf

    2015-12-01

    The exocrine pancreas exhibits a distinctive capacity for tissue regeneration and renewal following injury. This regenerative ability has important implications for a variety of disorders, including pancreatitis and pancreatic cancer, diseases associated with high morbidity and mortality. Thus, understanding its underlying mechanisms may help in developing therapeutic interventions. Serotonin has been recognized as a potent mitogen for a variety of cells and tissues. Here we investigated whether serotonin exerts a mitogenic effect in pancreatic acinar cells in three regenerative models, inflammatory tissue injury following pancreatitis, tissue loss following partial pancreatectomy, and thyroid hormone-stimulated acinar proliferation. Genetic and pharmacological techniques were used to modulate serotonin levels in vivo. Acinar dedifferentiation and cell cycle progression during the regenerative phase were investigated over the course of 2 weeks. By comparing acinar proliferation in the different murine models of regeneration, we found that serotonin did not affect the clonal regeneration of mature acinar cells. Serotonin was, however, required for acinar dedifferentiation following inflammation-mediated tissue injury. Specifically, lack of serotonin resulted in delayed up-regulation of progenitor genes and delayed the formation of acinar-to-ductal metaplasia and defective acinar cell proliferation. We identified serotonin-dependent acinar secretion as a key step in progenitor-based regeneration, as it promoted acinar cell dedifferentiation and the recruitment of type 2 macrophages. Finally, we identified a regulatory Hes1-Ptfa axis in the uninjured adult pancreas, activated by zymogen secretion. Our findings indicated that serotonin plays a critical role in the regeneration of the adult pancreas following pancreatitis by promoting the dedifferentiation of acinar cells. PMID:26235267

  8. Effects of hypothyroidism on the ultrastructure of rat pancreatic acinar cells: a stereological analysis

    OpenAIRE

    Blanco-Molina, A.; González-Reyes, J. A.; Torre-Cisneros, J; López-Miranda, J.; Nicolás, M.; Pérez-Jiménez, F.

    1991-01-01

    The morphological and stereological characteristics of the exocrine pancreas subcellular organelles from healthy and thyroidectomized rats have been studied. The acinar tissue from hypothyroid rats showed an interstitial edema and evidence of degenerative processes. Stereological parameters of zymogen granules were significantly reduced in thyroidectomized rats. The hypothyroidism induced degenerative changes in the pancreatic acinar cells as well as a decr...

  9. Pancreatic acinar cells: molecular insight from studies of signal-transduction using transgenic animals.

    Science.gov (United States)

    Yule, David I

    2010-11-01

    Pancreatic acinar cells are classical exocrine gland cells. The apical regions of clusters of coupled acinar cells collectively form a lumen which constitutes the blind end of a tube created by ductal cells - a structure reminiscent of a "bunch of grapes". When activated by neural or hormonal secretagogues, pancreatic acinar cells are stimulated to secrete a variety of proteins. These proteins are predominately inactive digestive enzyme precursors called "zymogens". Acinar cell secretion is absolutely dependent on secretagogue-induced increases in intracellular free Ca(2+). The increase in [Ca(2+)](i) has precise temporal and spatial characteristics as a result of the exquisite regulation of the proteins responsible for Ca(2+) release, Ca(2+) influx and Ca(2+) clearance in the acinar cell. This brief review discusses recent studies in which transgenic animal models have been utilized to define in molecular detail the components of the Ca(2+) signaling machinery which contribute to these characteristics.

  10. A computer-based automated algorithm for assessing acinar cell loss after experimental pancreatitis.

    Directory of Open Access Journals (Sweden)

    John F Eisses

    Full Text Available The change in exocrine mass is an important parameter to follow in experimental models of pancreatic injury and regeneration. However, at present, the quantitative assessment of exocrine content by histology is tedious and operator-dependent, requiring manual assessment of acinar area on serial pancreatic sections. In this study, we utilized a novel computer-generated learning algorithm to construct an accurate and rapid method of quantifying acinar content. The algorithm works by learning differences in pixel characteristics from input examples provided by human experts. HE-stained pancreatic sections were obtained in mice recovering from a 2-day, hourly caerulein hyperstimulation model of experimental pancreatitis. For training data, a pathologist carefully outlined discrete regions of acinar and non-acinar tissue in 21 sections at various stages of pancreatic injury and recovery (termed the "ground truth". After the expert defined the ground truth, the computer was able to develop a prediction rule that was then applied to a unique set of high-resolution images in order to validate the process. For baseline, non-injured pancreatic sections, the software demonstrated close agreement with the ground truth in identifying baseline acinar tissue area with only a difference of 1% ± 0.05% (p = 0.21. Within regions of injured tissue, the software reported a difference of 2.5% ± 0.04% in acinar area compared with the pathologist (p = 0.47. Surprisingly, on detailed morphological examination, the discrepancy was primarily because the software outlined acini and excluded inter-acinar and luminal white space with greater precision. The findings suggest that the software will be of great potential benefit to both clinicians and researchers in quantifying pancreatic acinar cell flux in the injured and recovering pancreas.

  11. Cathepsin B Activity Initiates Apoptosis via Digestive Protease Activation in Pancreatic Acinar Cells and Experimental Pancreatitis.

    Science.gov (United States)

    Sendler, Matthias; Maertin, Sandrina; John, Daniel; Persike, Maria; Weiss, F Ulrich; Krüger, Burkhard; Wartmann, Thomas; Wagh, Preshit; Halangk, Walter; Schaschke, Norbert; Mayerle, Julia; Lerch, Markus M

    2016-07-01

    Pancreatitis is associated with premature activation of digestive proteases in the pancreas. The lysosomal hydrolase cathepsin B (CTSB) is a known activator of trypsinogen, and its deletion reduces disease severity in experimental pancreatitis. Here we studied the activation mechanism and subcellular compartment in which CTSB regulates protease activation and cellular injury. Cholecystokinin (CCK) increased the activity of CTSB, cathepsin L, trypsin, chymotrypsin, and caspase 3 in vivo and in vitro and induced redistribution of CTSB to a secretory vesicle-enriched fraction. Neither CTSB protein nor activity redistributed to the cytosol, where the CTSB inhibitors cystatin-B/C were abundantly present. Deletion of CTSB reduced and deletion of cathepsin L increased intracellular trypsin activation. CTSB deletion also abolished CCK-induced caspase 3 activation, apoptosis-inducing factor, as well as X-linked inhibitor of apoptosis protein degradation, but these depended on trypsinogen activation via CTSB. Raising the vesicular pH, but not trypsin inhibition, reduced CTSB activity. Trypsin inhibition did not affect apoptosis in hepatocytes. Deletion of CTSB affected apoptotic but not necrotic acinar cell death. In summary, CTSB in pancreatitis undergoes activation in a secretory, vesicular, and acidic compartment where it activates trypsinogen. Its deletion or inhibition regulates acinar cell apoptosis but not necrosis in two models of pancreatitis. Caspase 3-mediated apoptosis depends on intravesicular trypsinogen activation induced by CTSB, not CTSB activity directly, and this mechanism is pancreas-specific. PMID:27226576

  12. Protein kinase D1 drives pancreatic acinar cell reprogramming and progression to intraepithelial neoplasia

    Science.gov (United States)

    Liou, Geou-Yarh; Döppler, Heike; Braun, Ursula B.; Panayiotou, Richard; Scotti Buzhardt, Michele; Radisky, Derek C.; Crawford, Howard C.; Fields, Alan P.; Murray, Nicole R.; Wang, Q. Jane; Leitges, Michael; Storz, Peter

    2015-02-01

    The transdifferentiation of pancreatic acinar cells to a ductal phenotype (acinar-to-ductal metaplasia, ADM) occurs after injury or inflammation of the pancreas and is a reversible process. However, in the presence of activating Kras mutations or persistent epidermal growth factor receptor (EGF-R) signalling, cells that underwent ADM can progress to pancreatic intraepithelial neoplasia (PanIN) and eventually pancreatic cancer. In transgenic animal models, ADM and PanINs are initiated by high-affinity ligands for EGF-R or activating Kras mutations, but the underlying signalling mechanisms are not well understood. Here, using a conditional knockout approach, we show that protein kinase D1 (PKD1) is sufficient to drive the reprogramming process to a ductal phenotype and progression to PanINs. Moreover, using 3D explant culture of primary pancreatic acinar cells, we show that PKD1 acts downstream of TGFα and Kras, to mediate formation of ductal structures through activation of the Notch pathway.

  13. A Patient of Pancreatic Acinar Cell Carcinoma with Dilated Esophagogastric Vessels

    Directory of Open Access Journals (Sweden)

    Masakuni Fujii

    2015-07-01

    Full Text Available Left portal hypertension and splenic vein occlusion commonly occur with pancreatic tumors, however these signs are rarely observed in patients with acinar cell carcinoma. This report describes a rare left portal hypertension in a patient who presented with a dilated esophagogastric vein upon esophagogastroduodenoscopic examination of a gastric polyp. A contrast-enhanced computed tomography scan revealed a pancreatic tumor, with obstruction of the splenic vein and portal-systemic shunt. The patient was diagnosed with an acinar cell carcinoma of the pancreatic tail. This patient highlights that pancreatic acinar cell carcinoma should be considered as a differential diagnosis in patients with a dilated esophagogastric vein and without signs of liver disease.

  14. Inactivation of TGFβ receptor II signalling in pancreatic epithelial cells promotes acinar cell proliferation, acinar-to-ductal metaplasia and fibrosis during pancreatitis.

    Science.gov (United States)

    Grabliauskaite, Kamile; Saponara, Enrica; Reding, Theresia; Bombardo, Marta; Seleznik, Gitta M; Malagola, Ermanno; Zabel, Anja; Faso, Carmen; Sonda, Sabrina; Graf, Rolf

    2016-02-01

    Determining signalling pathways that regulate pancreatic regeneration following pancreatitis is critical for implementing therapeutic interventions. In this study we elucidated the molecular mechanisms underlying the effects of transforming growth factor-β (TGFβ) in pancreatic epithelial cells during tissue regeneration. To this end, we conditionally inactivated TGFβ receptor II (TGFβ-RII) using a Cre-LoxP system under the control of pancreas transcription factor 1a (PTF1a) promoter, specific for the pancreatic epithelium, and evaluated the molecular and cellular changes in a mouse model of cerulein-induced pancreatitis. We show that TGFβ-RII signalling does not mediate the initial acinar cell damage observed at the onset of pancreatitis. However, TGFβ-RII signalling not only restricts acinar cell replication during the regenerative phase of the disease but also limits ADM formation in vivo and in vitro in a cell-autonomous manner. Analyses of molecular mechanisms underlying the observed phenotype revealed that TGFβ-RII signalling stimulates the expression of cyclin-dependent kinase inhibitors and intersects with the EGFR signalling axis. Finally, TGFβ-RII ablation in epithelial cells resulted in increased infiltration of inflammatory cells in the early phases of pancreatitis and increased activation of pancreatic stellate cells in the later stages of pancreatitis, thus highlighting a TGFβ-based crosstalk between epithelial and stromal cells regulating the development of pancreatic inflammation and fibrosis. Collectively, our data not only contribute to clarifying the cellular processes governing pancreatic tissue regeneration, but also emphasize the conserved role of TGFβ as a tumour suppressor, both in the regenerative process following pancreatitis and in the initial phases of pancreatic cancer.

  15. Inactivation of TGFβ receptor II signalling in pancreatic epithelial cells promotes acinar cell proliferation, acinar-to-ductal metaplasia and fibrosis during pancreatitis.

    Science.gov (United States)

    Grabliauskaite, Kamile; Saponara, Enrica; Reding, Theresia; Bombardo, Marta; Seleznik, Gitta M; Malagola, Ermanno; Zabel, Anja; Faso, Carmen; Sonda, Sabrina; Graf, Rolf

    2016-02-01

    Determining signalling pathways that regulate pancreatic regeneration following pancreatitis is critical for implementing therapeutic interventions. In this study we elucidated the molecular mechanisms underlying the effects of transforming growth factor-β (TGFβ) in pancreatic epithelial cells during tissue regeneration. To this end, we conditionally inactivated TGFβ receptor II (TGFβ-RII) using a Cre-LoxP system under the control of pancreas transcription factor 1a (PTF1a) promoter, specific for the pancreatic epithelium, and evaluated the molecular and cellular changes in a mouse model of cerulein-induced pancreatitis. We show that TGFβ-RII signalling does not mediate the initial acinar cell damage observed at the onset of pancreatitis. However, TGFβ-RII signalling not only restricts acinar cell replication during the regenerative phase of the disease but also limits ADM formation in vivo and in vitro in a cell-autonomous manner. Analyses of molecular mechanisms underlying the observed phenotype revealed that TGFβ-RII signalling stimulates the expression of cyclin-dependent kinase inhibitors and intersects with the EGFR signalling axis. Finally, TGFβ-RII ablation in epithelial cells resulted in increased infiltration of inflammatory cells in the early phases of pancreatitis and increased activation of pancreatic stellate cells in the later stages of pancreatitis, thus highlighting a TGFβ-based crosstalk between epithelial and stromal cells regulating the development of pancreatic inflammation and fibrosis. Collectively, our data not only contribute to clarifying the cellular processes governing pancreatic tissue regeneration, but also emphasize the conserved role of TGFβ as a tumour suppressor, both in the regenerative process following pancreatitis and in the initial phases of pancreatic cancer. PMID:26510396

  16. Constitutive IKK2 activation in acinar cells is sufficient to induce pancreatitis in vivo

    OpenAIRE

    Baumann, Bernd; Wagner, Martin; Aleksic, Tamara; von Wichert, Götz; Weber, Christoph K.; Adler, Guido; Wirth, Thomas

    2007-01-01

    Activation of the inhibitor of NF-κB kinase/NF-κB (IKK/NF-κB) system and expression of proinflammatory mediators are major events in acute pancreatitis. However, the in vivo consequences of IKK activation on the onset and progression of acute pancreatitis remain unclear. Therefore, we modulated IKK activity conditionally in pancreatic acinar cells. Transgenic mice expressing the reverse tetracycline-responsive transactivator (rtTA) gene under the control of the rat elastase promoter were gene...

  17. Analysis and Optimization of Nutritional Set-up for Murine Pancreatic Acinar Cells.

    Directory of Open Access Journals (Sweden)

    Kurup S

    2002-01-01

    Full Text Available CONTEXT: Pancreatic acinar cell cultivation poses a serious problem due to limitations in the in vitro survival time despite variations of dissociation protocols, culture media and nutrient supplements. OBJECTIVE: To establish a long term culture of murine pancreatic acinar cells which retain their viability, monolayer formation and responsiveness to secretagogues. In order to investigate the mechanism of the short-life of acinar cells studied in vitro, we studied their survival under the influence of different supplements on nutrient media. INTERVENTIONS: Dissociated pancreatic acini were prepared from BALB/c mice pancreata by collagenase digestion supplemented with bovine serum albumin fraction V and soybean trypsin inhibitor. A nutrient set-up was designed for their long term survival in vitro. RESULTS: It was observed that mouse pancreatic acinar cells dissociated in presence of bovine serum albumin fraction V and soybean trypsin inhibitor result in 95% viability. Further cultivation of these acinar cells in Waymouth's MB 752/1 medium supplemented with 10% fetal calf serum (v/v, soybean trypsin inhibitor, bovine serum albumin, dexamethasone, and epidermal growth factor results in their survival for more than 6 days in culture with 85% viability, retention of the secretagogue responsiveness and formation of a monolayer without any extracellular matrix coating. CONCLUSIONS: Our study clearly demonstrates that the addition of soybean trypsin inhibitor to culture medium reduces zymogen granule fragility and acinar cell death, thus increasing their viability for sufficiently long periods. The present study offers an excellent, in vitro model for the investigation of exocrine dysfunction in response to acinar cell injury.

  18. Acinar cell apoptosis in Serpini2-deficient mice models pancreatic insufficiency.

    Directory of Open Access Journals (Sweden)

    Stacie K Loftus

    2005-09-01

    Full Text Available Pancreatic insufficiency (PI when left untreated results in a state of malnutrition due to an inability to absorb nutrients. Frequently, PI is diagnosed as part of a larger clinical presentation in cystic fibrosis or Shwachman-Diamond syndrome. In this study, a mouse model for isolated exocrine PI was identified in a mouse line generated by a transgene insertion. The trait is inherited in an autosomal recessive pattern, and homozygous animals are growth retarded, have abnormal immunity, and have reduced life span. Mice with the disease locus, named pequeño (pq, exhibit progressive apoptosis of pancreatic acinar cells with severe exocrine acinar cell loss by 8 wk of age, while the islets and ductal tissue persist. The mutation in pq/pq mice results from a random transgene insertion. Molecular characterization of the transgene insertion site by fluorescent in situ hybridization and genomic deletion mapping identified an approximately 210-kb deletion on Chromosome 3, deleting two genes. One of these genes, Serpini2, encodes a protein that is a member of the serpin family of protease inhibitors. Reintroduction of only the Serpini2 gene by bacterial artificial chromosome transgenic complementation corrected the acinar cell defect as well as body weight and immune phenotypes, showing that deletion of Serpini2 causes the pequeño phenotype. Dietary supplementation of pancreatic enzymes also corrected body size, body weight, and immunodeficiency, and increased the life span of Serpini2-deficient mice, despite continued acinar cell loss. To our knowledge, this study describes the first characterized genetic animal model for isolated PI. Genetic complementation of the transgene insertion mutant demonstrates that Serpini2 deficiency directly results in the acinar cell apoptosis, malabsorption, and malnutrition observed in pq/pq mice. The rescue of growth retardation, immunodeficiency, and mortality by either Serpini2 bacterial artificial chromosome

  19. Acinar Cell Apoptosis in Serpini2-DeficientMice Models Pancreatic Insufficiency.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available Pancreatic insufficiency (PI when left untreated results in a state of malnutrition due to an inability to absorb nutrients. Frequently, PI is diagnosed as part of a larger clinical presentation in cystic fibrosis or Shwachman-Diamond syndrome. In this study, a mouse model for isolated exocrine PI was identified in a mouse line generated by a transgene insertion. The trait is inherited in an autosomal recessive pattern, and homozygous animals are growth retarded, have abnormal immunity, and have reduced life span. Mice with the disease locus, named pequeño (pq, exhibit progressive apoptosis of pancreatic acinar cells with severe exocrine acinar cell loss by 8 wk of age, while the islets and ductal tissue persist. The mutation in pq/pq mice results from a random transgene insertion. Molecular characterization of the transgene insertion site by fluorescent in situ hybridization and genomic deletion mapping identified an approximately 210-kb deletion on Chromosome 3, deleting two genes. One of these genes, Serpini2, encodes a protein that is a member of the serpin family of protease inhibitors. Reintroduction of only the Serpini2 gene by bacterial artificial chromosome transgenic complementation corrected the acinar cell defect as well as body weight and immune phenotypes, showing that deletion of Serpini2 causes the pequeño phenotype. Dietary supplementation of pancreatic enzymes also corrected body size, body weight, and immunodeficiency, and increased the life span of Serpini2-deficient mice, despite continued acinar cell loss. To our knowledge, this study describes the first characterized genetic animal model for isolated PI. Genetic complementation of the transgene insertion mutant demonstrates that Serpini2 deficiency directly results in the acinar cell apoptosis, malabsorption, and malnutrition observed in pq/pq mice. The rescue of growth retardation, immunodeficiency, and mortality by either Serpini2 bacterial artificial chromosome

  20. Modelling the transition from simple to complex Ca2+ oscillations in pancreatic acinar cells

    Indian Academy of Sciences (India)

    Neeraj Manhas; James Sneyd; K R Pardasani

    2014-06-01

    A mathematical model is proposed which systematically investigates complex calcium oscillations in pancreatic acinar cells. This model is based on calcium-induced calcium release via inositol trisphosphate receptors (IPR) and ryanodine receptors (RyR) and includes calcium modulation of inositol (1,4,5) trisphosphate (IP3) levels through feedback regulation of degradation and production. In our model, the apical and the basal regions are separated by a region containing mitochondria, which is capable of restricting Ca2+ responses to the apical region. We were able to reproduce the observed oscillatory patterns, from baseline spikes to sinusoidal oscillations. The model predicts that calcium-dependent production and degradation of IP3 is a key mechanism for complex calcium oscillations in pancreatic acinar cells. A partial bifurcation analysis is performed which explores the dynamic behaviour of the model in both apical and basal regions.

  1. Organelle selection determines agonist-specific Ca2+ signals in pancreatic acinar and beta cells

    OpenAIRE

    Yamasaki, M.; Masgrau, R.; Morgan, A. J.; Churchill, G. C.; Patel, S.; Ashcroft, S. J. H.; Galione, A

    2004-01-01

    How different extracellular stimuli can evoke different spatiotemporal Ca2+ signals is uncertain. We have elucidated a novel paradigm whereby different agonists use different Ca2+-storing organelles ("organelle seleetion") to evoke unique responses. Some agonists select the endoplasmic reticulum (ER), and others select lysosome-related (acidic) organelles, evoking spatial Ca2+ responses that mirror the organellar distribution. In pancreatic acinar cells, acetylcholine and bombesin exclusively...

  2. Pancreatic panniculitis in a patient with pancreatic-type acinar cell carcinoma of the liver – case report and review of literature

    OpenAIRE

    Zundler, Sebastian; Erber, Ramona; Agaimy, Abbas; Hartmann, Arndt; Kiesewetter, Franklin; Strobel, Deike; Neurath, Markus F; Wildner, Dane

    2016-01-01

    Background Pancreatic panniculitis is a rare condition, which has only been described in relation with pancreatic diseases up to now. It is characterized by necrotizing subcutaneous inflammation and is thought to be triggered by adipocyte necrosis due to systemic release of pancreatic enzymes with consecutive infiltration of neutrophils. We present the first case of a patient with pancreatic panniculitis caused by pancreatic-type primary acinar cell carcinoma (ACC) of the liver and without un...

  3. Regulating effects of arsenic trioxide on cell death pathways and inflammatory reactions of pancreatic acinar cells in rats

    Institute of Scientific and Technical Information of China (English)

    XUE Dong-bo; ZHANG Wei-hui; YUN Xiao-guang; SONG Chun; ZHENG Biao; SHI Xing-ye; WANG Hai-yang

    2007-01-01

    Background It is accepted that inflammatory cytokines play a key role in the development of acute pancreatitis, so blocking the initiation of inflammatory reactions may alleviate pathological changes of acute pancreatitis. We studied the regulatory effect of arsenic trioxide (As2O3) on apoptosis and oncosis of pancreatic acinar cells in vitro and in vivo and its therapeutic effect on acute pancreatitis.Methods Pancreatic acinar cells were isolated by collagenase digestion method. Apoptosis and oncosis of isolated pancreatic acinar cells were detected with Hoechst 33258+PI or Annexin V+PI double fluorescent staining. Amylase and lactate dehydrogenase release were measured. Acute pancreatitis was induced in Wistar rats by intraperitoneal injections of caerulein, and apoptosis was detected with terminal dUTP nick-end labeling method. Tumor necorsis factor α (TNF-α) mRNA, myeloperoxidase, nuclear factor-κB and histological grading of pancreatic damage were measured.Results There was an increased apoptosis but a decreased oncosis of pancreatic acinar cell after the treatment with As2O3. The levels of lactate dehydrogenase and amylase release were markedly decreased in As2O3 treated group.Myeloperoxidase content, TNF-α mRNA level, nuclear factor-κB activation and pathological score in As2O3 treated group were significantly lower than in the untreated group.Conclusions As2O3 can induce apoptosis and reduce oncosis of pancreatic acinar cell, thus resulting in reduced release of endocellular enzyme of acinar cells, reduced inflammatory cell infiltration and decreased the production of inflammatory cytokines, so that the outcome of alleviated pathological changes was finally achieved.

  4. Acinar-to-ductal metaplasia accompanies c-myc-induced exocrine pancreatic cancer progression in transgenic rodents.

    Science.gov (United States)

    Grippo, Paul J; Sandgren, Eric P

    2012-09-01

    Several important characteristics of exocrine pancreatic tumor pathogenesis remain incompletely defined, including identification of the cell of origin. Most human pancreatic neoplasms are ductal adenocarcinomas. However, acinar cells have been proposed as the source of some ductal neoplasms through a process of acinar-to-ductal metaplasia. The oncogenic transcription factor c-myc is associated with human pancreatic neoplasms. Transgenic mice overexpressing c-myc under control of acinar cell-specific elastase (Ela) gene regulatory elements not only develop acinar cell carcinomas but also mixed neoplasms that display both acinar-like neoplastic cells and duct-like neoplastic cells. In this report, we demonstrate that, first, c-myc is sufficient to induce acinar hyperplasia, though neoplastic lesions develop focally. Second, cell proliferation remains elevated in the neoplastic duct cell compartment of mixed neoplasms. Third, the proliferation/apoptosis ratio in cells from all lesion types remains constant, suggesting that differential regulation of these processes is not a feature of cancer progression in this model. Fourth, before the development of mixed neoplasms, there is transcriptional activation of the duct cell-specific cytokeratin-19 gene promoter in multicellular foci of amylase-positive acinar neoplasms. This observation provides direct evidence for metaplasia as the mechanism underlying development of ductal neoplastic cells within the context of an acinar neoplasm and suggests that the stimulus for this transformation acts over a multicellular domain or field within a neoplasm. Finally, focal ductal elements develop in some acinar cell carcinomas in Ela-c-myc transgenic rats, indicating that myc-associated acinar-to-ductal metaplasia is not restricted to the mouse.

  5. A tetanus toxin sensitive protein other than VAMP 2 is required for exocytosis in the pancreatic acinar cell.

    Science.gov (United States)

    Padfield, P J

    2000-11-01

    The neurotoxin sensitivity of regulated exocytosis in the pancreatic acinar cell was investigated using streptolysin-O permeabilized pancreatic acini. Treatment of permeabilized acini with botulinum toxin B (BoNT/B) or botulinum toxin D (BoNT/D) had no detectable effect on Ca(2+)-dependent amylase secretion but did result in the complete cleavage of VAMP 2. In comparison, tetanus toxin (TeTx) treatment both significantly inhibited Ca(2+)-dependent amylase secretion and cleaved VAMP 2. These results indicate that regulated exocytosis in the pancreatic acinar cell requires a tetanus toxin sensitive protein(s) other than VAMP 2.

  6. Coupling of guanine nucleotide inhibitory protein to somatostatin receptors on pancreatic acinar membranes

    International Nuclear Information System (INIS)

    Guanine nucleotides and pertussis toxin were used to investigate whether somatostatin receptors interact with the guanine nucleotide inhibitory protein (NI) on pancreatic acinar membranes in the rat. Guanine nucleotides reduced 125I-[Tyr1]somatostatin binding to acinar membranes up to 80%, with rank order of potency being 5'-guanylyl imidodiphosphate [Gpp(NH)p]>GTP>TDP>GMP. Scatchard analysis revealed that the decrease in somatostatin binding caused by Gpp(NH)p was due to the decrease in the maximum binding capacity without a significant change in the binding affinity. The inhibitory effect of Gpp(NH)p was partially abolished in the absence of Mg2+. When pancreatic acini were treated with 1 μg/ml pertussis toxin for 4 h, subsequent 125I-[Tyr1]somatostatin binding to acinar membranes was reduced. Pertussis toxin treatment also abolished the inhibitory effect of somatostatin on vasoactive intestinal peptide-stimulated increase in cellular content of adenosine 3',5'-cyclic monophosphate (cAMP) in the acini. The present results suggest that 1) somatostatin probably functions in the pancreas to regulate adenylate cyclase enzyme system via Ni, 2) the extent of modification of Ni is correlated with the ability of somatostatin to inhibit cAMP accumulation in acini, and 3) guanine nucleotides also inhibit somatostatin binding to its receptor

  7. FDG PET imaging of Ela1-myc mice reveals major biological differences between pancreatic acinar and ductal tumours

    Energy Technology Data Exchange (ETDEWEB)

    Abasolo, Ibane [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Universitat Pompeu Fabra, Parc de Recerca Biomedica de Barcelona, Departament de Ciencies Experimentals i de la Salut, Barcelona (Spain); Institut d' Alta Tecnologia - CRC, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Pujal, Judit; Navarro, Pilar [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Rabanal, Rosa M.; Serafin, Anna [Universitat Autonoma de Barcelona, Departament de Medicina i Cirurgia Animals, Barcelona (Spain); Millan, Olga [Institut d' Alta Tecnologia - CRC, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Real, Francisco X. [Institut Municipal d' Investigacio Medica-Hospital del Mar, Parc de Recerca Biomedica de Barcelona, Barcelona (Spain); Universitat Pompeu Fabra, Parc de Recerca Biomedica de Barcelona, Departament de Ciencies Experimentals i de la Salut, Barcelona (Spain); Programa de Patologia Molecular, Centro Nacional de Investigaciones Oncologicas, Madrid (Spain)

    2009-07-15

    The aim was to evaluate FDG PET imaging in Ela1-myc mice, a pancreatic cancer model resulting in the development of tumours with either acinar or mixed acinar-ductal phenotype. Transversal and longitudinal FDG PET studies were conducted; selected tissue samples were subjected to autoradiography and ex vivo organ counting. Glucose transporter and hexokinase mRNA expression was analysed by quantitative reverse transcription polymerase chain reaction (RT-PCR); Glut2 expression was analysed by immunohistochemistry. Transversal studies showed that mixed acinar-ductal tumours could be identified by FDG PET several weeks before they could be detected by hand palpation. Longitudinal studies revealed that ductal - but not acinar - tumours could be detected by FDG PET. Autoradiographic analysis confirmed that tumour areas with ductal differentiation incorporated more FDG than areas displaying acinar differentiation. Ex vivo radioactivity measurements showed that tumours of solely acinar phenotype incorporated more FDG than pancreata of non-transgenic littermates despite the fact that they did not yield positive PET images. To gain insight into the biological basis of the differential FDG uptake, glucose transporter and hexokinase transcript expression was studied in microdissected tumour areas enriched for acinar or ductal cells and validated using cell-specific markers. Glut2 and hexokinase I and II mRNA levels were up to 20-fold higher in ductal than in acinar tumours. Besides, Glut2 protein overexpression was found in ductal neoplastic cells but not in the surrounding stroma. In Ela1-myc mice, ductal tumours incorporate significantly more FDG than acinar tumours. This difference likely results from differential expression of Glut2 and hexokinases. These findings reveal previously unreported biological differences between acinar and ductal pancreatic tumours. (orig.)

  8. Effects of Baicalin on inflammatory mediators and pancreatic acinar cell apoptosis in rats with sever acute pancreatitis

    Directory of Open Access Journals (Sweden)

    zhang xiping

    2009-02-01

    Full Text Available

    • BACKGROUND: To investigate the effects of Baicalin and Octreotide on inflammatory mediators and pancreatic acinar cells apoptosis of rats with severe acute pancreatitis (SAP.
    • METHODS: SD rats were randomly divided into sham operated group (I group, model control group (II group, Baicalin treated group (III group and Octreotide treated group (IV group. Each group was also divided into subgroup of 3, 6 and 12 h (n = 15. The mortality rate, ascites/body weight ratio as well as the level of endotoxin, NO and ET-1 in blood were measured. The pathological severity score of pancreas, apoptotic indexes, and expression levels of Bax and Bcl-2 proteins in each group were investigated.
    • RESULTS: The survival rate of III and IV group has a significant difference compared with II group (P12 h < 0.05. The ascites volume, contents of inflammatory mediators in blood and pathological severity score of pancreas of III and IV group declined at different degrees compared to II group (P < 0.05, P < 0.01 or P < 0.001. Apoptotic index in III group was significantly higher than that in II group at 3 and 6 h (P3, 6 h < 0.05. Apoptotic index in IV group was significantly higher than that in II group at pancreatic tail at 6 h (P6 h < 0.05. Expression level of Bax in III group was significantly higher than that in II group (pancreatic head P3 h,6 h < 0.01, pancreatic tail P3 h < 0.001.
    • CONCLUSIONS: Compared with Octreotide in the treatment of SAP, the protective mechanisms of Baicalin include reducing the excessive inflammatory mediators’ release, inducing the pancreatic acinar cells apoptosis.
    • KEY WORDS: Severe acute pancreatitis, baicalin, octreotide, inflammatory mediators, apoptosis, tissue microarrays.

  9. p21(WAF1) (/Cip1) limits senescence and acinar-to-ductal metaplasia formation during pancreatitis.

    Science.gov (United States)

    Grabliauskaite, Kamile; Hehl, Adrian B; Seleznik, Gitta M; Saponara, Enrica; Schlesinger, Kathryn; Zuellig, Richard A; Dittmann, Anja; Bain, Martha; Reding, Theresia; Sonda, Sabrina; Graf, Rolf

    2015-02-01

    Trans-differentiation of pancreatic acinar cells into ductal-like lesions, a process defined as acinar-to-ductal metaplasia (ADM), is observed in the course of organ regeneration following pancreatitis. In addition, ADM is found in association with pre-malignant PanIN lesions and correlates with an increased risk of pancreatic adenocarcinoma (PDAC). Human PDAC samples show down-regulation of p21(WAF1) (/Cip1) , a key regulator of cell cycle and cell differentiation. Here we investigated whether p21 down-regulation is implicated in controlling the early events of acinar cell trans-differentiation and ADM formation. p21-mediated regulation of ADM formation and regression was analysed in vivo during the course of cerulein-induced pancreatitis, using wild-type (WT) and p21-deficient (p21(-/-) ) mice. Biochemical and immunohistochemical methods were used to evaluate disease progression over 2 weeks of the disease and during a recovery phase. We found that p21 was strongly up-regulated in WT acinar cells during pancreatitis, while it was absent in ADM areas, suggesting that p21 down-regulation is associated with ADM formation. In support of this hypothesis, p21(-/-) mice showed a significant increase in number and size of metaplasia. In addition, p21 over-expression in acinar cells reduced ADM formation in vitro, suggesting that the protein regulates the metaplastic transition in a cell-autonomous manner. p21(-/-) mice displayed increased expression and relocalization of β-catenin both during pancreatitis and in the subsequent recovery phase. Finally, loss of p21 was accompanied by increased DNA damage and development of senescence. Our findings are consistent with a gate-keeper role of p21 in acinar cells to limit senescence activation and ADM formation during pancreatic regeneration. PMID:25212177

  10. Genetic ablation of Smoothened in pancreatic fibroblasts increases acinar-ductal metaplasia.

    Science.gov (United States)

    Liu, Xin; Pitarresi, Jason R; Cuitiño, Maria C; Kladney, Raleigh D; Woelke, Sarah A; Sizemore, Gina M; Nayak, Sunayana G; Egriboz, Onur; Schweickert, Patrick G; Yu, Lianbo; Trela, Stefan; Schilling, Daniel J; Halloran, Shannon K; Li, Maokun; Dutta, Shourik; Fernandez, Soledad A; Rosol, Thomas J; Lesinski, Gregory B; Shakya, Reena; Ludwig, Thomas; Konieczny, Stephen F; Leone, Gustavo; Wu, Jinghai; Ostrowski, Michael C

    2016-09-01

    The contribution of the microenvironment to pancreatic acinar-to-ductal metaplasia (ADM), a preneoplastic transition in oncogenic Kras-driven pancreatic cancer progression, is currently unclear. Here we show that disruption of paracrine Hedgehog signaling via genetic ablation of Smoothened (Smo) in stromal fibroblasts in a Kras(G12D) mouse model increased ADM. Smo-deleted fibroblasts had higher expression of transforming growth factor-α (Tgfa) mRNA and secreted higher levels of TGFα, leading to activation of EGFR signaling in acinar cells and increased ADM. The mechanism involved activation of AKT and noncanonical activation of the GLI family transcription factor GLI2. GLI2 was phosphorylated at Ser230 in an AKT-dependent fashion and directly regulated Tgfa expression in fibroblasts lacking Smo Additionally, Smo-deleted fibroblasts stimulated the growth of Kras(G12D)/Tp53(R172H) pancreatic tumor cells in vivo and in vitro. These results define a non-cell-autonomous mechanism modulating Kras(G12D)-driven ADM that is balanced by cross-talk between Hedgehog/SMO and AKT/GLI2 pathways in stromal fibroblasts. PMID:27633013

  11. Epiplakin deficiency aggravates murine caerulein-induced acute pancreatitis and favors the formation of acinar keratin granules.

    Directory of Open Access Journals (Sweden)

    Karl L Wögenstein

    Full Text Available Epiplakin, a member of the plakin protein family, is exclusively expressed in epithelial tissues and was shown to bind to keratins. Epiplakin-deficient (EPPK-/- mice showed no obvious spontaneous phenotype, however, EPPK-/- keratinocytes displayed faster keratin network breakdown in response to stress. The role of epiplakin in pancreas, a tissue with abundant keratin expression, was not yet known. We analyzed epiplakin's expression in healthy and inflamed pancreatic tissue and compared wild-type and EPPK-/- mice during caerulein-induced acute pancreatitis. We found that epiplakin was expressed primarily in ductal cells of the pancreas and colocalized with apicolateral keratin bundles in murine pancreatic acinar cells. Epiplakin's diffuse subcellular localization in keratin filament-free acini of K8-deficient mice indicated that its filament-associated localization in acinar cells completely depends on its binding partner keratin. During acute pancreatitis, epiplakin was upregulated in acinar cells and its redistribution closely paralleled keratin reorganization. EPPK-/- mice suffered from aggravated pancreatitis but showed no obvious regeneration phenotype. At the most severe stage of the disease, EPPK-/- acinar cells displayed more keratin aggregates than those of wild-type mice. Our data propose epiplakin to be a protective protein during acute pancreatitis, and that its loss causes impaired disease-associated keratin reorganization.

  12. Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca2+ oscillations in mouse pancreatic acinar cells

    Science.gov (United States)

    Huang, Zebing; Wang, Haiyan; Wang, Jingke; Zhao, Mengqin; Sun, Nana; Sun, Fangfang; Shen, Jianxin; Zhang, Haiying; Xia, Kunkun; Chen, Dejie; Gao, Ming; Hammer, Ronald P.; Liu, Qingrong; Xi, Zhengxiong; Fan, Xuegong; Wu, Jie

    2016-01-01

    Emerging evidence demonstrates that the blockade of intracellular Ca2+ signals may protect pancreatic acinar cells against Ca2+ overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca2+ signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca2+ oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB2Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca2+ oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca2+ oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca2+ oscillations and L-arginine-induced enhancement of Ca2+ signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis. PMID:27432473

  13. Cannabinoid receptor subtype 2 (CB2R) agonist, GW405833 reduces agonist-induced Ca(2+) oscillations in mouse pancreatic acinar cells.

    Science.gov (United States)

    Huang, Zebing; Wang, Haiyan; Wang, Jingke; Zhao, Mengqin; Sun, Nana; Sun, Fangfang; Shen, Jianxin; Zhang, Haiying; Xia, Kunkun; Chen, Dejie; Gao, Ming; Hammer, Ronald P; Liu, Qingrong; Xi, Zhengxiong; Fan, Xuegong; Wu, Jie

    2016-01-01

    Emerging evidence demonstrates that the blockade of intracellular Ca(2+) signals may protect pancreatic acinar cells against Ca(2+) overload, intracellular protease activation, and necrosis. The activation of cannabinoid receptor subtype 2 (CB2R) prevents acinar cell pathogenesis in animal models of acute pancreatitis. However, whether CB2Rs modulate intracellular Ca(2+) signals in pancreatic acinar cells is largely unknown. We evaluated the roles of CB2R agonist, GW405833 (GW) in agonist-induced Ca(2+) oscillations in pancreatic acinar cells using multiple experimental approaches with acute dissociated pancreatic acinar cells prepared from wild type, CB1R-knockout (KO), and CB2R-KO mice. Immunohistochemical labeling revealed that CB2R protein was expressed in mouse pancreatic acinar cells. Electrophysiological experiments showed that activation of CB2Rs by GW reduced acetylcholine (ACh)-, but not cholecystokinin (CCK)-induced Ca(2+) oscillations in a concentration-dependent manner; this inhibition was prevented by a selective CB2R antagonist, AM630, or was absent in CB2R-KO but not CB1R-KO mice. In addition, GW eliminated L-arginine-induced enhancement of Ca(2+) oscillations, pancreatic amylase, and pulmonary myeloperoxidase. Collectively, we provide novel evidence that activation of CB2Rs eliminates ACh-induced Ca(2+) oscillations and L-arginine-induced enhancement of Ca(2+) signaling in mouse pancreatic acinar cells, which suggests a potential cellular mechanism of CB2R-mediated protection in acute pancreatitis. PMID:27432473

  14. Transgenic Expression of a Single Transcription Factor Pdx1 Induces Transdifferentiation of Pancreatic Acinar Cells to Endocrine Cells in Adult Mice.

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    Miyazaki, Satsuki; Tashiro, Fumi; Miyazaki, Jun-Ichi

    2016-01-01

    A promising approach to new diabetes therapies is to generate β cells from other differentiated pancreatic cells in vivo. Because the acinar cells represent the most abundant cell type in the pancreas, an attractive possibility is to reprogram acinar cells into β cells. The transcription factor Pdx1 (Pancreas/duodenum homeobox protein 1) is essential for pancreatic development and cell lineage determination. Our objective is to examine whether exogenous expression of Pdx1 in acinar cells of adult mice might induce reprogramming of acinar cells into β cells. We established a transgenic mouse line in which Pdx1 and EGFP (enhanced green fluorescent protein) could be inducibly expressed in the acinar cells. After induction of Pdx1, we followed the acinar cells for their expression of exocrine and endocrine markers using cell-lineage tracing with EGFP. The acinar cell-specific expression of Pdx1 in adult mice reprogrammed the acinar cells as endocrine precursor cells, which migrated into the pancreatic islets and differentiated into insulin-, somatostatin-, or PP (pancreatic polypeptide)-producing endocrine cells, but not into glucagon-producing cells. When the mice undergoing such pancreatic reprogramming were treated with streptozotocin (STZ), the newly generated insulin-producing cells were able to ameliorate STZ-induced diabetes. This paradigm of in vivo reprogramming indicates that acinar cells hold promise as a source for new islet cells in regenerative therapies for diabetes. PMID:27526291

  15. Transgenic Expression of a Single Transcription Factor Pdx1 Induces Transdifferentiation of Pancreatic Acinar Cells to Endocrine Cells in Adult Mice

    Science.gov (United States)

    Miyazaki, Satsuki; Tashiro, Fumi; Miyazaki, Jun-ichi

    2016-01-01

    A promising approach to new diabetes therapies is to generate β cells from other differentiated pancreatic cells in vivo. Because the acinar cells represent the most abundant cell type in the pancreas, an attractive possibility is to reprogram acinar cells into β cells. The transcription factor Pdx1 (Pancreas/duodenum homeobox protein 1) is essential for pancreatic development and cell lineage determination. Our objective is to examine whether exogenous expression of Pdx1 in acinar cells of adult mice might induce reprogramming of acinar cells into β cells. We established a transgenic mouse line in which Pdx1 and EGFP (enhanced green fluorescent protein) could be inducibly expressed in the acinar cells. After induction of Pdx1, we followed the acinar cells for their expression of exocrine and endocrine markers using cell-lineage tracing with EGFP. The acinar cell-specific expression of Pdx1 in adult mice reprogrammed the acinar cells as endocrine precursor cells, which migrated into the pancreatic islets and differentiated into insulin-, somatostatin-, or PP (pancreatic polypeptide)-producing endocrine cells, but not into glucagon-producing cells. When the mice undergoing such pancreatic reprogramming were treated with streptozotocin (STZ), the newly generated insulin-producing cells were able to ameliorate STZ-induced diabetes. This paradigm of in vivo reprogramming indicates that acinar cells hold promise as a source for new islet cells in regenerative therapies for diabetes. PMID:27526291

  16. Genetic deletion of Rab27B in pancreatic acinar cells affects granules size and has inhibitory effects on amylase secretion.

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    Hou, Yanan; Ernst, Stephen A; Lentz, Stephen I; Williams, John A

    2016-03-18

    Small G protein Rab27B is expressed in various secretory cell types and plays a role in mediating secretion. In pancreatic acinar cells, Rab27B was found to be expressed on the zymogen granule membrane and by overexpression to regulate the secretion of zymogen granules. However, the effect of Rab27B deletion on the physiology of pancreatic acinar cells is unknown. In the current study, we utilized the Rab27B KO mouse model to better understand the role of Rab27B in the secretion of pancreatic acinar cells. Our data show that Rab27B deficiency had no obvious effects on the expression of major digestive enzymes and other closely related proteins, e.g. similar small G proteins, such as Rab3D and Rab27A, and putative downstream effectors. The overall morphology of acinar cells was not changed in the knockout pancreas. However, the size of zymogen granules was decreased in KO acinar cells, suggesting a role of Rab27B in regulating the maturation of secretory granules. The secretion of digestive enzymes was moderately decreased in KO acini, compared with the WT control. These data indicate that Rab27B is involved at a different steps of zymogen granule maturation and secretion, which is distinct from that of Rab3D.

  17. KLF4 Is Essential for Induction of Cellular Identity Change and Acinar-to-Ductal Reprogramming during Early Pancreatic Carcinogenesis.

    Science.gov (United States)

    Wei, Daoyan; Wang, Liang; Yan, Yongmin; Jia, Zhiliang; Gagea, Mihai; Li, Zhiwei; Zuo, Xiangsheng; Kong, Xiangyu; Huang, Suyun; Xie, Keping

    2016-03-14

    Understanding the molecular mechanisms of tumor initiation has significant impact on early cancer detection and intervention. To define the role of KLF4 in pancreatic ductal adenocarcinoma (PDA) initiation, we used molecular biological analyses and mouse models of klf4 gain- and loss-of-function and mutant Kras. KLF4 is upregulated in and required for acinar-to-ductal metaplasia. Klf4 ablation drastically attenuates the formation of pancreatic intraepithelial neoplasia induced by mutant Kras(G12D), whereas upregulation of KLF4 does the opposite. Mutant KRAS and cellular injuries induce KLF4 expression, and ectopic expression of KLF4 in acinar cells reduces acinar lineage- and induces ductal lineage-related marker expression. These results demonstrate that KLF4 induces ductal identity in PanIN initiation and may be a potential target for prevention of PDA initiation.

  18. Different cell death modes of pancreatic acinar cells on macrophage activation in rats

    Institute of Scientific and Technical Information of China (English)

    LIANG Tao; LIU Tie-fu; XUE Dong-bo; SUN Bei; SHI Li-jun

    2008-01-01

    Background The pathogenesis of acute pancreatitis is complex and largely unclear. The aim of this study was to explore the relationship between modes of cell death in pancreatic acinar cells, the release of cell contents and the inflammatory response of macrophagas.Methods Our experiment included four groups: group A (the control group), group B (AR42J cells overstimulated by caerulein), group C (AR42J cells treated with lipopolysaccharide and caerulein), and group D (AR42J cells treated with octreotide and caerulein). Apoptosis and oncosis, and the release of amylase and lactate dehydrogenase (LDH) from AR42J cells were detected. Rat macrophages were stimulated by 1 ml supematant of culture medium of AR42J cells.Finally, NF-кB activation and TNF-α and IL-1β secretion by macrophages were detected.Results Oncotlc cells in group C increased while apoptctic cells decreased (P <0.05); cells in group D had the inverse reaction. The release of amylase and LDH changed directly with the occurrence of oncosis. The transcription factor NF-кB was activated and secretion of TNF-α and IL-1β were significantly higher in group C than in group B (P <0.05); in group D, these actions were significantly lower than in group B (P<0.05). This trend was in line with changes in amylase and LDH production.Conclusion There is a close relationship between modes of pancreatic acinar cell death, the release of cell contents and the inflammatory reaction of macrophages.

  19. Cleavage of SNAP-25 and VAMP-2 impairs store-operated Ca2+ entry in mouse pancreatic acinar cells.

    Science.gov (United States)

    Rosado, Juan A; Redondo, Pedro C; Salido, Ginés M; Sage, Stewart O; Pariente, Jose A

    2005-01-01

    We recently reported that store-operated Ca(2+) entry (SOCE) in nonexcitable cells is likely to be mediated by a reversible interaction between Ca(2+) channels in the plasma membrane and the endoplasmic reticulum, a mechanism known as "secretion-like coupling." As for secretion, in this model the actin cytoskeleton plays a key regulatory role. In the present study we have explored the involvement of the secretory proteins synaptosome-associated protein (SNAP-25) and vesicle-associated membrane protein (VAMP) in SOCE in pancreatic acinar cells. Cleavage of SNAP-25 and VAMPs by treatment with botulinum toxin A (BoNT A) and tetanus toxin (TeTx), respectively, effectively inhibited amylase secretion stimulated by the physiological agonist CCK-8. BoNT A significantly reduced Ca(2+) entry induced by store depletion using thapsigargin or CCK-8. In addition, treatment with BoNT A once SOCE had been activated reduced Ca(2+) influx, indicating that SNAP-25 is needed for both the activation and maintenance of SOCE in pancreatic acinar cells. VAMP-2 and VAMP-3 are expressed in mouse pancreatic acinar cells. Both proteins associate with the cytoskeleton upon Ca(2+) store depletion, although only VAMP-2 seems to be sensitive to TeTx. Treatment of pancreatic acinar cells with TeTx reduced the activation of SOCE without affecting its maintenance. These findings support a role for SNAP-25 and VAMP-2 in the activation of SOCE in pancreatic acinar cells and show parallels between this process and secretion in a specialized secretory cell type.

  20. Lysosome associated membrane proteins maintain pancreatic acinar cell homeostasis : LAMP-2 deficient mice develop pancreatitis

    NARCIS (Netherlands)

    Mareninova, Olga A; Sendler, Matthias; Malla, Sudarshan Ravi; Yakubov, Iskandar; French, Samuel W; Tokhtaeva, Elmira; Vagin, Olga; Oorschot, Viola; Lüllmann-Rauch, Renate; Blanz, Judith; Dawson, David; Klumperman, Judith; Lerch, Markus M; Mayerle, Julia; Gukovsky, Ilya; Gukovskaya, Anna S

    2015-01-01

    BACKGROUND & AIMS: The pathogenic mechanism of pancreatitis is poorly understood. Recent evidence implicates defective autophagy in pancreatitis responses; however, the pathways mediating impaired autophagy in pancreas remain largely unknown. Here, we investigate the role of lysosome associated memb

  1. Mutant KRas-Induced Mitochondrial Oxidative Stress in Acinar Cells Upregulates EGFR Signaling to Drive Formation of Pancreatic Precancerous Lesions

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    Geou-Yarh Liou

    2016-03-01

    Full Text Available The development of pancreatic cancer requires the acquisition of oncogenic KRas mutations and upregulation of growth factor signaling, but the relationship between these is not well established. Here, we show that mutant KRas alters mitochondrial metabolism in pancreatic acinar cells, resulting in increased generation of mitochondrial reactive oxygen species (mROS. Mitochondrial ROS then drives the dedifferentiation of acinar cells to a duct-like progenitor phenotype and progression to PanIN. This is mediated via the ROS-receptive kinase protein kinase D1 and the transcription factors NF-κB1 and NF-κB2, which upregulate expression of the epidermal growth factor, its ligands, and their sheddase ADAM17. In vivo, interception of KRas-mediated generation of mROS reduced the formation of pre-neoplastic lesions. Hence, our data provide insight into how oncogenic KRas interacts with growth factor signaling to induce the formation of pancreatic cancer.

  2. Alcohol oxidizing enzymes and ethanol-induced cytotoxicity in rat pancreatic acinar AR42J cells.

    Science.gov (United States)

    Bhopale, Kamlesh K; Falzon, Miriam; Ansari, G A S; Kaphalia, Bhupendra S

    2014-04-01

    Alcoholic chronic pancreatitis (ACP) is a serious inflammatory disease causing significant morbidity and mortality. Due to lack of a suitable animal model, the underlying mechanism of ACP is poorly understood. Chronic alcohol abuse inhibits alcohol dehydrogenase (ADH) and facilitates nonoxidative metabolism of ethanol to fatty acid ethyl esters (FAEEs) in the pancreas frequently damaged during chronic ethanol abuse. Earlier, we reported a concentration-dependent formation of FAEEs and cytotoxicity in ethanol-treated rat pancreatic tumor (AR42J) cells, which express high FAEE synthase activity as compared to ADH and cytochrome P450 2E1. Therefore, the present study was undertaken to investigate the role of various ethanol oxidizing enzymes in ethanol-induced pancreatic acinar cell injury. Confluent AR42J cells were pre-treated with inhibitors of ADH class I and II [4-methylpyrazole (MP)] or class I, II, and III [1,10-phenanthroline (PT)], cytochrome P450 2E1 (trans-1,2-dichloroethylene) or catalase (sodium azide) followed by incubation with 800 mg% ethanol at 37°C for 6 h. Ethanol metabolism, cell viability, cytotoxicity (apoptosis and necrosis), cell proliferation status, and formation of FAEEs in AR42J cells were measured. The cell viability and cell proliferation rate were significantly reduced in cells pretreated with 1,10-PT + ethanol followed by those with 4-MP + ethanol. In situ formation of FAEEs was twofold greater in cells incubated with 1,10-PT + ethanol and ∼1.5-fold in those treated with 4-MP + ethanol vs. respective controls. However, cells treated with inhibitors of cytochrome P450 2E1 or catalase in combination of ethanol showed no significant changes either for FAEE formation, cell death or proliferation rate. Therefore, an impaired ADH class I-III catalyzed oxidation of ethanol appears to be a key contributing factor in ethanol-induced pancreatic injury via formation of nonoxidative metabolites of ethanol.

  3. Alcohol oxidizing enzymes and ethanol-induced cytotoxicity in rat pancreatic acinar AR42J cells

    Science.gov (United States)

    Bhopale, Kamlesh K.; Falzon, Miriam; Ansari, G. A. S.

    2016-01-01

    Alcoholic chronic pancreatitis (ACP) is a serious inflammatory disease causing significant morbidity and mortality. Due to lack of a suitable animal model, the underlying mechanism of ACP is poorly understood. Chronic alcohol abuse inhibits alcohol dehydrogenase (ADH) and facilitates nonoxidative metabolism of ethanol to fatty acid ethyl esters (FAEEs) in the pancreas frequently damaged during chronic ethanol abuse. Earlier, we reported a concentration-dependent formation of FAEEs and cytotoxicity in ethanol-treated rat pancreatic tumor (AR42J) cells, which express high FAEE synthase activity as compared to ADH and cytochrome P450 2E1. Therefore, the present study was undertaken to investigate the role of various ethanol oxidizing enzymes in ethanol-induced pancreatic acinar cell injury. Confluent AR42J cells were pre-treated with inhibitors of ADH class I and II [4-methylpyrazole (MP)] or class I, II, and III [1,10-phenanthroline (PT)], cytochrome P450 2E1 (trans-1,2-dichloroethylene) or catalase (sodium azide) followed by incubation with 800 mg% ethanol at 37°C for 6 h. Ethanol metabolism, cell viability, cytotoxicity (apoptosis and necrosis), cell proliferation status, and formation of FAEEs in AR42J cells were measured. The cell viability and cell proliferation rate were significantly reduced in cells pretreated with 1,10-PT + ethanol followed by those with 4-MP + ethanol. In situ formation of FAEEs was twofold greater in cells incubated with l,10-PT + ethanol and ~1.5-fold in those treated with 4-MP + ethanol vs. respective controls. However, cells treated with inhibitors of cytochrome P450 2E1 or catalase in combination of ethanol showed no significant changes either for FAEE formation, cell death or proliferation rate. Therefore, an impaired ADH class I—III catalyzed oxidation of ethanol appears to be a key contributing factor in ethanol-induced pancreatic injury via formation of nonoxidative metabolites of ethanol. PMID:24281792

  4. Directed pancreatic acinar differentiation of mouse embryonic stem cells via embryonic signalling molecules and exocrine transcription factors.

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    Fabien Delaspre

    Full Text Available Pluripotent embryonic stem cells (ESC are a promising cellular system for generating an unlimited source of tissue for the treatment of chronic diseases and valuable in vitro differentiation models for drug testing. Our aim was to direct differentiation of mouse ESC into pancreatic acinar cells, which play key roles in pancreatitis and pancreatic cancer. To that end, ESC were first differentiated as embryoid bodies and sequentially incubated with activin A, inhibitors of Sonic hedgehog (Shh and bone morphogenetic protein (BMP pathways, fibroblast growth factors (FGF and retinoic acid (RA in order to achieve a stepwise increase in the expression of mRNA transcripts encoding for endodermal and pancreatic progenitor markers. Subsequent plating in Matrigel® and concomitant modulation of FGF, glucocorticoid, and folllistatin signalling pathways involved in exocrine differentiation resulted in a significant increase of mRNAs encoding secretory enzymes and in the number of cells co-expressing their protein products. Also, pancreatic endocrine marker expression was down-regulated and accompanied by a significant reduction in the number of hormone-expressing cells with a limited presence of hepatic marker expressing-cells. These findings suggest a selective activation of the acinar differentiation program. The newly differentiated cells were able to release α-amylase and this feature was greatly improved by lentiviral-mediated expression of Rbpjl and Ptf1a, two transcription factors involved in the maximal production of digestive enzymes. This study provides a novel method to produce functional pancreatic exocrine cells from ESC.

  5. A resected case of symptomatic acinar cell cystadenoma of the pancreas displacing the main pancreatic duct.

    Science.gov (United States)

    Tanaka, Haruyoshi; Hatsuno, Tsuyoshi; Kinoshita, Mitsuru; Hasegawa, Kazuya; Ishihara, Hiromasa; Takano, Nao; Shimoyama, Satofumi; Nakayama, Hiroshi; Kataoka, Masato; Ichihara, Shu; Kanda, Mitsuro; Kodera, Yasuhiro; Kondo, Ken

    2016-12-01

    Acinar cell cystadenoma (ACA) of the pancreas has been newly recognized as an entity by the World Health Organization (WHO) definition (2010), and its pathogenesis has not been known adequately because of the rarity. Here, we report a case of a 22-year-old female who had been followed up for a cystic lesion at the tail of the pancreas pointed out by a screening computed tomography (CT) scan 7 years ago. The tumor grew in size from 3.3 to 5.1 cm in diameter for 6 years (0.3 cm per year). Particularly, it rapidly grew up to 6.3 cm in the latest 3 months in concurrence with the emergence of epigastralgia. A contrasted CT scan revealed the irregularly formed, multilocular cystic tumor having thin septum and calcification. The intratumoral magnetic resonance imaging intensity in the T1 and T2 weighted images were low and high, respectively. No communications between the tumor and the main pancreatic duct (MPD) were found, but the tumor displaced the MPD. She underwent surgical resection because the tumor was growing, turned symptomatic, and it seemed difficult to be diagnosed correctly until totally biopsied. Spleen-preserved distal pancreatectomy was performed. It was pathologically diagnosed as ACA; the cyst was lined by cells with normal acinar differentiation; cuboidal cells with round, basally oriented nuclei and eosinophilic granules in its apical cytoplasm. The abdominal pain has disappeared, and no recurrences have been found during a 5-year follow-up. Clinicians are recommended to consider an ACA as one of differential diagnoses of cystic tumors of the pancreas to provide appropriate diagnostics and therapeutics. PMID:27108123

  6. Rab27A Is Present in Mouse Pancreatic Acinar Cells and Is Required for Digestive Enzyme Secretion.

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    Yanan Hou

    Full Text Available The small G-protein Rab27A has been shown to regulate the intracellular trafficking of secretory granules in various cell types. However, the presence, subcellular localization and functional impact of Rab27A on digestive enzyme secretion by mouse pancreatic acinar cells are poorly understood. Ashen mice, which lack the expression of Rab27A due to a spontaneous mutation, were used to investigate the function of Rab27A in pancreatic acinar cells. Isolated pancreatic acini were prepared from wild-type or ashen mouse pancreas by collagenase digestion, and CCK- or carbachol-induced amylase secretion was measured. Secretion occurring through the major-regulated secretory pathway, which is characterized by zymogen granules secretion, was visualized by Dextran-Texas Red labeling of exocytotic granules. The minor-regulated secretory pathway, which operates through the endosomal/lysosomal pathway, was characterized by luminal cell surface labeling of lysosomal associated membrane protein 1 (LAMP1. Compared to wild-type, expression of Rab27B was slightly increased in ashen mouse acini, while Rab3D and digestive enzymes (amylase, lipase, chymotrypsin and elastase were not affected. Localization of Rab27B, Rab3D and amylase by immunofluorescence was similar in both wild-type and ashen acinar cells. The GTP-bound states of Rab27B and Rab3D in wild-type and ashen mouse acini also remained similar in amount. In contrast, acini from ashen mice showed decreased amylase release induced by CCK- or carbachol. Rab27A deficiency reduced the apical cell surface labeling of LAMP1, but did not affect that of Dextran-Texas Red incorporation into the fusion pockets at luminal surface. These results show that Rab27A is present in mouse pancreatic acinar cells and mainly regulates secretion through the minor-regulated pathway.

  7. Atp2c2 Is Transcribed From a Unique Transcriptional Start Site in Mouse Pancreatic Acinar Cells.

    Science.gov (United States)

    Fenech, Melissa A; Sullivan, Caitlin M; Ferreira, Lucimar T; Mehmood, Rashid; MacDonald, William A; Stathopulos, Peter B; Pin, Christopher L

    2016-12-01

    Proper regulation of cytosolic Ca(2+) is critical for pancreatic acinar cell function. Disruptions in normal Ca(2+) concentrations affect numerous cellular functions and are associated with pancreatitis. Membrane pumps and channels regulate cytosolic Ca(2+) homeostasis by promoting rapid Ca(2+) movement. Determining how expression of Ca(2+) modulators is regulated and the cellular alterations that occur upon changes in expression can provide insight into initiating events of pancreatitis. The goal of this study was to delineate the gene structure and regulation of a novel pancreas-specific isoform for Secretory Pathway Ca(2+) ATPase 2 (termed SPCA2C), which is encoded from the Atp2c2 gene. Using Next Generation Sequencing of RNA (RNA-seq), chromatin immunoprecipitation for epigenetic modifications and promoter-reporter assays, a novel transcriptional start site was identified that promotes expression of a transcript containing the last four exons of the Atp2c2 gene (Atp2c2c). This region was enriched for epigenetic marks and pancreatic transcription factors that promote gene activation. Promoter activity for regions upstream of the ATG codon in Atp2c2's 24th exon was observed in vitro but not in in vivo. Translation from this ATG encodes a protein aligned with the carboxy terminal of SPCA2. Functional analysis in HEK 293A cells indicates a unique role for SPCA2C in increasing cytosolic Ca(2+) . RNA analysis indicates that the decreased Atp2c2c expression observed early in experimental pancreatitis reflects a global molecular response of acinar cells to reduce cytosolic Ca(2+) levels. Combined, these results suggest SPCA2C affects Ca(2+) homeostasis in pancreatic acinar cells in a unique fashion relative to other Ca(2+) ATPases. J. Cell. Physiol. 231: 2768-2778, 2016. © 2016 Wiley Periodicals, Inc. PMID:27017909

  8. Damage to pancreatic acinar cells and preservation of islets of Langerhans in a rat model of acute pancreatitis induced by Karwinskia humboldtiana (buckthorn).

    Science.gov (United States)

    Carcano-Diaz, Katya; Garcia-Garcia, Aracely; Segoviano-Ramirez, Juan Carlos; Rodriguez-Rocha, Humberto; Loera-Arias, Maria de Jesus; Garcia-Juarez, Jaime

    2016-09-01

    Karwinskia humboldtiana (Kh) is a poisonous plant that grows in some regions of the American continent. Consuming large amounts of Kh fruit results in acute intoxication leading to respiratory failure, culminating in death within days. There is evidence of histological damage to the lungs, liver, and kidneys following accidental and experimental Kh intoxication. To date, the microscopic effect of Kh consumption on the pancreas has not been described. We examined the early effects of Kh fruit on pancreatic tissue at different stages of acute intoxication in the Wistar rat. We found progressive damage confined to the exocrine pancreas, starting with a reduction in the number of zymogen granules, loss of acinar architecture, the presence of autophagy-like vesicles, apoptosis and inflammatory infiltrate. The pancreatic pathology culminated in damaged acini characterized by necrosis and edema, with a complete loss of lobular architecture. Interestingly, the morphology of the islets of Langerhans was conserved throughout our evaluations. Taken together, our results indicate the damage induced by a high dose of Kh fruit in the Wistar rat is consistent with an early acute necrotizing pancreatitis that exclusively affects the exocrine pancreas. Therefore, this system might be useful as an animal model to study the treatment of pancreatic diseases. More importantly, as the islets of Langerhans were preserved, the active compounds of Kh fruit could be utilized for the treatment of acinar pancreatic cancer. Further studies might provide insight into the severity of acute Kh intoxication in humans and influence the design of treatments for pancreatic diseases and acinar pancreatic cancer. PMID:26877198

  9. Slug inhibits pancreatic cancer initiation by blocking Kras-induced acinar-ductal metaplasia

    OpenAIRE

    Kazumi Ebine; Chow, Christina R.; DeCant, Brian T.; Hattaway, Holly Z.; Grippo, Paul J.; Krishan Kumar; Munshi, Hidayatullah G.

    2016-01-01

    Cells in the pancreas that have undergone acinar-ductal metaplasia (ADM) can transform into premalignant cells that can eventually become cancerous. Although the epithelial-mesenchymal transition regulator Snail (Snai1) can cooperate with Kras in acinar cells to enhance ADM development, the contribution of Snail-related protein Slug (Snai2) to ADM development is not known. Thus, transgenic mice expressing Slug and Kras in acinar cells were generated. Surprisingly, Slug attenuated Kras-induced...

  10. β-catenin is selectively required for the expansion and regeneration of mature pancreatic acinar cells in mice

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    Matthew D. Keefe

    2012-07-01

    The size of the pancreas is determined by intrinsic factors, such as the number of progenitor cells, and by extrinsic signals that control the fate and proliferation of those progenitors. Both the exocrine and endocrine compartments of the pancreas undergo dramatic expansion after birth and are capable of at least partial regeneration following injury. Whether the expansion of these lineages relies on similar mechanisms is unknown. Although we have shown that the Wnt signaling component β-catenin is selectively required in mouse embryos for the generation of exocrine acinar cells, this protein has been ascribed various functions in the postnatal pancreas, including proliferation and regeneration of islet as well as acinar cells. To address whether β-catenin remains important for the maintenance and expansion of mature acinar cells, we have established a system to follow the behavior and fate of β-catenin-deficient cells during postnatal growth and regeneration in mice. We find that β-catenin is continuously required for the establishment and maintenance of acinar cell mass, extending from embryonic specification through juvenile and adult self-renewal and regeneration. This requirement is not shared with islet cells, which proliferate and function normally in the absence of β-catenin. These results make distinct predictions for the relative role of Wnt–β-catenin signaling in the etiology of human endocrine and exocrine disease. We suggest that loss of Wnt–β-catenin activity is unlikely to drive islet dysfunction, as occurs in type 2 diabetes, but that β-catenin is likely to promote human acinar cell proliferation following injury, and might therefore contribute to the resolution of acute or chronic pancreatitis.

  11. A comparison study of pancreatic acinar cell carcinoma with ductal adenocarcinoma using computed tomography in Chinese patients

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    Wang Q

    2016-09-01

    Full Text Available Qingbing Wang,1,2 Xiaolin Wang,1,2 Rongfang Guo,2,3 Guoping Li1,2 1Department of Interventional Radiology, Zhongshan Hospital, Fudan University, 2Shanghai Institute of Medical Imaging, 3Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China Abstract: Pancreatic acinar cell carcinoma (ACC is a rare tumor that is difficult to diagnose preoperatively. The aim of this study was to evaluate and describe the computed tomography (CT features of ACC and compare the results with pancreatic ductal adenocarcinoma (DAC for improving preoperative diagnosis. The control group consisted of 34 patients with DAC collected from the pathology electronic database. The CT imaging from nine patients with pathologically confirmed ACC was retrospectively reviewed. Two radiologists independently assessed the tumor location, size, texture, and enhancement patterns. We found that 64.3% (9/14 of ACC tumors were homogeneous and 35.7% (5/14 had necrosis. The percentage of common bile duct and pancreatic ductal dilation was 14.3% (2/14 and 7.1% (1/14, respectively. The mean size of ACC was 50.1±24.2 mm. The mean attenuation of ACC was 35.4±3.9 Hounsfield unit (HU before enhancement, 73.1±42.9 HU in arterial phase, and 71.8±15.6 HU in port venous phase. It is difficult to distinguish ACC from DAC preoperatively only based on CT findings. However, compared with DAC, we found that ACC tumors are likely to be larger and contain more heterogeneous intratumoral necrotic hypovascular regions, and less pancreatic ductal and common biliary dilation. Keywords: acinar cell carcinoma, computed tomography, pancreatic ductal carcinoma, pancreas

  12. Involvement of M3 Cholinergic Receptor Signal Transduction Pathway in Regulation of the Expression of Chemokine MOB-1, MCP-1 Genes in Pancreatic Acinar Cells

    Institute of Scientific and Technical Information of China (English)

    郑海; 陈道达; 张景輝; 田原

    2004-01-01

    Whether M3 cholinergic receptor signal transduction pathway is involved in regulation of the activation of NF-κB and the expression of chemokine MOB-1, MCP-1genes in pancreatic acinar cells was investigated. Rat pancreatic acinar cells were isolated, cultured and treated with carbachol, atropine and PDTC in vitro. The MOB-1 and MCP-1 mRNA expression was detected by using RT-PCR. The activation of NF-κB was monitored by using electrophoretic mobility shift assay.The results showed that as compared with control group, M3 cholinergic receptor agonist (103mol/L, 104-4ol/L carbachol) could induce a concentration-dependent and time-dependent increase in the expression of MOB-1, MCP-1 mRNA in pancreatic acinar cells. After treatment with 10 -3mol/L carbachol for 2 h, the expression of MOB-1, MCP-1 mRNA was strongest. The activity of NF-κB in pancreatic acinar cells was significantly increased (P<0.01) after treated with M3 cholinergic receptor agonist (10-3 mol/L carbachol) in vitro for 30 min. Either M3 cholinergic receptor antagonist (10-5 mol/L atropine) or NF-κB inhibitor (10-2 mol/L PDTC) could obviously inhibit the activation of NF-κB and the chemokine MOB-1, MCP-1 mRNA expression induced by carbachol (P <0.05). This inhibitory effect was significantly increased by atropine plus PDTC (P<0.01). The results of these studies indicated that M3 cholinergic receptor signal transduction pathway was likely involved in regulation of the expression of chemokine MOB-1 and MCP-1genes in pancreatic acinar cells in vitro through the activation of NF-κB.

  13. Knockdown of GRP78 promotes apoptosis in pancreatic acinar cells and attenuates the severity of cerulein and LPS induced pancreatic inflammation.

    Directory of Open Access Journals (Sweden)

    Yong Liu

    Full Text Available Acute pancreatitis (AP is a potentially lethal disease characterized by inflammation and parenchymal cell death; also, the severity of AP correlates directly with necrosis and inversely with apoptosis. However, mechanisms of regulating cell death in AP remain unclear. The endoplasmic reticulum (ER chaperone protein GRP78 has anti-apoptotic properties, in addition to modulating ER stress responses. This study used RNA interference (RNAi approach to investigate the potential role of GRP78 in regulating apoptosis during AP. In vitro models of AP were successfully developed by treating AR42J cells with cerulein or cerulein plus lipoplysaccharide (LPS. There was more pancreatic inflammation and less apoptosis with the cerulein plus LPS treatment. Furthermore, knockdown of GRP78 expression markedly promoted apoptosis and reduced necrosis in pancreatic acinar cells. This was accomplished by enhancing the activation of caspases and inhibiting the activity of X-linked inhibitor of apoptosis protein (XIAP, as well as a receptor interacting protein kinase-1(RIPK1, which is a key mediator of necrosis. This attenuated the severity of pancreatic inflammation, especially after cerulein plus LPS treatment. In conclusion, these findings indicate that GRP78 plays an anti-apoptotic role in regulating the cell death response during AP. Therefore, GRP78 is a potential therapeutic target for AP.

  14. Characteristics and mechanism of enzyme secretion and increase in [ Ca2+ ]i in Saikosaponin(I) stimulated rat pancreatic acinar cells

    Institute of Scientific and Technical Information of China (English)

    Yi Yu; Wen-Xiu Yang; Hui Wang; Wen-Zheng Zhang; Bao-Hua Liu; Zhi-Yong Dong

    2002-01-01

    AIM: This investigation was to reveal the characteristics andmechanism of enzyme secretion and increase in [ Ca2+ ]1stimulated by saikosaponin(I) [ SA(I) ] in rat pancreatic acini.METHODS: Pancreatic acini were prepared from male Wistarrats. Isolated acinar cells were suspended in Eagle's MEMsolution. After adding drugs, the incubation was performedat 37 ℃ for a set period of time. Amylase of supernatant wasassayed using starch-iodide reaction. Isolated acinar singlecell was incubated with Fura-2/AMat 37 ℃, then cells werewashed and resuspended in fresh solution and attached tothe chamber. Cytoplasm [ Ca2+ ]i of a single cell wasexpressed by fluorescence ratio F340/F380 recorded in aNikon PI Ca2+ measurement system.RESULTS: Rate course of amylase secretion stimulated bySA(I) in rat pancreatic acini appeared in bell-like shape. Thepeak amplitude increased depended on SA(I) concentration.The maximum rate responded to 1 × 10-5 mol/L SA(I) was 13.1-fold of basal and the rate decreased to basal level at 30min. CCK-8 receptor antagonist Bt2-cGMP markedly inhibitedamylase secretion stimulated by SA (I) and the dose-effectrelationship was similar to that by CCK-8. [Ca2+ ]i in a singleacinar cell rose to the peak st 5 min after adding 5 × l06 mol/LSA(I) and was 5. 1-fold of basal level. In addition, there was asecondary increase after the initial peak. GDP could inhibitboth the rate of amylase secretion and rising of [Ca2+ ]istimulated by SA(I) in a single pancreatic acinar cell.CONCLUSION: SA (I) is highly efficient in promoting thesecretion of enzymes synthesized in rat pancreatic acini andraising intracellular [Ca2+ ]i. Signaling transduction pathwayof SA(I) involves activating special membrane receptor andincrease in cytoplasm [Ca2+ ]i sequentially.

  15. Pancreatic Acinar Cells Employ miRNAs as Mediators of Intercellular Communication to Participate in the Regulation of Pancreatitis-Associated Macrophage Activation.

    Science.gov (United States)

    Zhao, Yong; Wang, Hao; Lu, Ming; Qiao, Xin; Sun, Bei; Zhang, Weihui; Xue, Dongbo

    2016-01-01

    Macrophage activation plays an important role in the inflammatory response in acute pancreatitis. In the present study, the activation of AR42J pancreatic acinar cells was induced by taurolithocholate treatment. The results showed that the culture medium from the activated AR42J cells significantly enhanced NFκB activation in the macrophages compared to that without taurolithocholate treatment. Additionally, the precipitates obtained from ultracentrifugation of the culture media that were rich in exosomes were markedly more potent in activating macrophages compared with the supernatant fraction lacking exosomes. The results indicated that the mediators carried by the exosomes played important roles in macrophage activation. Exosomal miRNAs were extracted and examined using microarrays. A total of 115 differentially expressed miRNAs were identified, and 30 showed upregulated expression, while 85 displayed downregulated expression. Target genes of the differentially expressed miRNAs were predicted using TargetScan, MiRanda, and PicTar software programs. The putative target genes were subjected to KEGG functional analysis. The functions of the target genes were primarily enriched in MAPK pathways. Specifically, the target genes regulated macrophage activation through the TRAF6-TAB2-TAK1-NIK/IKK-NFκB pathway. As the mediators of signal transduction, miRNAs and their predicted target mRNAs regulate every step in the MAPK pathway. PMID:27546996

  16. Quantitative characterization of the protein contents of the exocrine pancreatic acinar cell by soft x-ray microscopy and advanced digital imaging methods

    Energy Technology Data Exchange (ETDEWEB)

    Loo Jr., Billy W.

    2000-06-09

    The study of the exocrine pancreatic acinar cell has been central to the development of models of many cellular processes, especially of protein transport and secretion. Traditional methods used to examine this system have provided a wealth of qualitative information from which mechanistic models have been inferred. However they have lacked the ability to make quantitative measurements, particularly of the distribution of protein in the cell, information critical for grounding of models in terms of magnitude and relative significance. This dissertation describes the development and application of new tools that were used to measure the protein content of the major intracellular compartments in the acinar cell, particularly the zymogen granule. Soft x-ray microscopy permits image formation with high resolution and contrast determined by the underlying protein content of tissue rather than staining avidity. A sample preparation method compatible with x-ray microscopy was developed and its properties evaluated. Automatic computerized methods were developed to acquire, calibrate, and analyze large volumes of x-ray microscopic images of exocrine pancreatic tissue sections. Statistics were compiled on the protein density of several organelles, and on the protein density, size, and spatial distribution of tens of thousands of zymogen granules. The results of these measurements, and how they compare to predictions of different models of protein transport, are discussed.

  17. Inhibition of pancreatic acinar mitochondrial thiamin pyrophosphate uptake by the cigarette smoke component 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone.

    Science.gov (United States)

    Srinivasan, Padmanabhan; Thrower, Edwin C; Gorelick, Fred S; Said, Hamid M

    2016-05-15

    Thiamin is essential for normal metabolism in pancreatic acinar cells (PAC) and is obtained from their microenvironment through specific plasma-membrane transporters, converted to thiamin pyrophosphate (TPP) in the cytoplasm, followed by uptake of TPP by mitochondria through the mitochondrial TPP (MTPP) transporter (MTPPT; product of SLC25A19 gene). TPP is essential for normal mitochondrial function. We examined the effect of long-term/chronic exposure of PAC in vitro (pancreatic acinar 266-6 cells) and in vivo (wild-type or transgenic mice carrying the SLC25A19 promoter) of the cigarette smoke toxin, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), on the MTPP uptake process. Our in vitro and in vivo findings demonstrate that NNK negatively affects MTPP uptake and reduced expression of MTPPT protein, MTPPT mRNA, and heterogenous nuclear RNA, as well as SLC25A19 promoter activity. The effect of NNK on Slc25a19 transcription was neither mediated by changes in expression of transcriptional factor NFY-1 (known to drive SLC25A19 transcription), nor due to changes in methylation profile of the Slc25a19 promoter. Rather, it appears to be due to changes in histone modifications that involve significant decreases in histone H3K4-trimethylation and H3K9-acetylation (activation markers). The effect of NNK on MTPPT function is mediated through the nonneuronal α7-nicotinic acetylcholine receptor (α7-nAChR), as indicated by both in vitro (using the nAChR antagonist mecamylamine) and in vivo (using an α7-nAchR(-/-) mouse model) studies. These findings demonstrate that chronic exposure of PAC to NNK negatively impacts PAC MTPP uptake. This effect appears to be exerted at the level of Slc25a19 transcription, involve epigenetic mechanism(s), and is mediated through the α7-nAchR. PMID:26999808

  18. Monoclonal Antibody 16D10 to the C-Terminal Domain of the Feto-Acinar Pancreatic Protein Binds to Membrane of Human Pancreatic Tumoral SOJ-6 Cells and Inhibits the Growth of Tumor Xenografts

    Directory of Open Access Journals (Sweden)

    Laurence Panicot-Dubois

    2004-11-01

    Full Text Available Feto-acinar pancreatic protein (FAPP characterized by mAbJ28 reactivity is a specific component associated with ontogenesis and behaves as an oncodevelopment-associated antigen. We attempted to determine whether pancreatic tumoral SOJ-6 cells are expressed at their surface FAPP antigens and to examine if specific antibodies directed against these FAPP epitopes could decrease the growth of pancreatic tumors in a mice model. For this purpose, we used specific antibodies against either the whole FAPP, the O-glycosylated C-terminal domain, or the N-terminal domain of the protein. Our results indicate that SOJ-6 cells expressed at their surface a 32-kDa peptide corresponding to the C-terminal domain of the FAPP. Furthermore, we show, by using endoproteinase Lys-C or geldanamycin, a drug able to impair the FAPP secretion, that this 32-kDa peptide expressed on the SOJ-6 cell surface comes from the degradation of the FAPP. Finally, an in vivo prospective study using a preventative tumor model in nude mice indicates that targeting this peptide by the use of mAb16D10 inhibits the growth of SOJ-6 xenografts. The specificity of mAb16D10 for pancreatic tumors and the possibility to obtain recombinant structures of mucin-like peptides recognized by mAb16D10 and mAbJ28 are promising tools in immunologic approaches to cure pancreatic cancers.

  19. Tissue microarrays in pathological examination of apoptotic acinar cells induced by dexamethasone in the pancreas of rats with severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Xi-Ping Zhang; Hua Tian; Bei Lu; Li Chen; Ru-Jun Xu; Ke-Yi Wang; Zhi-Wei Wang; Qi-Hui Cheng; Hai-Ping Shen

    2007-01-01

    BACKGROUND:The good therapeutic effects of large dose of dexamethasone on severe acute pancreatitis (SAP) patients have been proved. This study was designed to investigate the inlfuence of dexamethasone on apoptosis of acinar cells in the pancreas of rats with SAP and the protein expression of the apoptosis-regulating genes Bax and Bcl-2. METHODS: Ninety Sprague-Dawley rats with SAP were randomly divided into a model group and a dexamethasone treated group (45 rats in each group), and another 45 rats formed the sham operation group. Survival rates were calculated and gross pathological changes in the pancreas of each group were observed under a light microscope 3, 6 and 12 hours after operation. Tissue microarray technology was applied to prepare pancreatic tissue sections. The changes in Bax and Bcl-2 protein expression levels of pancreatic tissues from each group were assessed by immunohistochemical staining, and TUNEL staining was used to evaluate changes in apoptosis index. RESULTS: The model and treated groups did not differ in mortality at each time point. The pathological score for the pancreas in the treated group was signiifcantly lower than that in the model group at 3 and 6 hours. The positive rates of Bax protein expression in the head and tail of the pancreas in the treated group at all time points were all markedly higher than those of the model group. The positive rate of Bcl-2 protein expression in the head of the pancreas in the treated group was signiifcantly higher than that of the model group at 3 hours. TUNEL staining showed that the pancreas head and tail apoptosis indices of the treated group were markedly higher than those of the model group after 6 hours. CONCLUSIONS: Apoptosis may be a protective response to pancreatic cell injury. The mechanism of action of dexamethasone in treating SAP may be related to the apoptosis of acinar cells in the pancreas induced by apoptosis-regulating genes such as Bax and Bcl-2. The advantages of tissue

  20. Melatonin induces the expression of Nrf2-regulated antioxidant enzymes via PKC and Ca2+ influx activation in mouse pancreatic acinar cells.

    Science.gov (United States)

    Santofimia-Castaño, Patricia; Clea Ruy, Deborah; Garcia-Sanchez, Lourdes; Jimenez-Blasco, Daniel; Fernandez-Bermejo, Miguel; Bolaños, Juan P; Salido, Gines M; Gonzalez, Antonio

    2015-10-01

    The goal of this study was to evaluate the potential activation of the nuclear factor erythroid 2-related factor and the antioxidant-responsive element (Nrf2-ARE) signaling pathway in response to melatonin in isolated mouse pancreatic acinar cells. Changes in intracellular free Ca(2+) concentration were followed by fluorimetric analysis of fura-2-loaded cells. The activations of PKC and JNK were measured by Western blot analysis. Quantitative reverse transcription-polymerase chain reaction was employed to detect the expression of Nrf2-regulated antioxidant enzymes. Immunocytochemistry was employed to determine nuclear location of phosphorylated Nrf2, and the cellular redox state was monitored following MitoSOX Red-derived fluorescence. Our results show that stimulation of fura-2-loaded cells with melatonin (1 µM to 1 mM), in the presence of Ca(2+) in the extracellular medium, induced a slow and progressive increase of [Ca(2+)](c) toward a stable level. Melatonin did not inhibit the typical Ca(2+) response induced by CCK-8 (1 nM). When the cells were challenged with indoleamine in the absence of Ca(2+) in the extracellular solution (medium containing 0.5 mM EGTA) or in the presence of 1 mM LaCl(3), to inhibit Ca(2+) entry, we could not detect any change in [Ca(2+)](c). Nevertheless, CCK-8 (1 nM) was able to induce the typical mobilization of Ca(2+). When the cells were incubated with the PKC activator PMA (1 µM) in the presence of Ca(2+) in the extracellular medium, we observed a response similar to that noted when the cells were challenged with melatonin 100 µM. However, in the presence of Ro31-8220 (3 µM), a PKC inhibitor, stimulation of cells with melatonin failed to evoke changes in [Ca(2+)]c. Immunoblots, using an antibody specific for phospho-PKC, revealed that melatonin induces PKCα activation, either in the presence or in the absence of external Ca(2+). Melatonin induced the phosphorylation and nuclear translocation of the transcription factor Nrf2, and

  1. Adult pancreatic acinar cells give rise to ducts but not endocrine cells in response to growth factor signaling

    OpenAIRE

    Blaine, Stacy A.; Ray, Kevin C.; Anunobi, Reginald; Gannon, Maureen A.; Washington, Mary K.; Means, Anna L.

    2010-01-01

    Studies in both humans and rodents have found that insulin+ cells appear within or near ducts of the adult pancreas, particularly following damage or disease, suggesting that these insulin+ cells arise de novo from ductal epithelium. We have found that insulin+ cells are continuous with duct cells in the epithelium that makes up the hyperplastic ducts of both chronic pancreatitis and pancreatic cancer in humans. Therefore, we tested the hypothesis that both hyperplastic ductal cells and their...

  2. Acinar Cell Carcinoma of the Pancreas

    Institute of Scientific and Technical Information of China (English)

    Hua Li; Qiang Li

    2008-01-01

    Acinar cell carcinoma of the pancreas is a rare tumor which is defined as a carcinoma that exhibits pancreatic enzyme production by neoplastic cells. This review includes re-cent developments in our understanding of the epidemiology and pathogenesis of ACC, imaging and pathological diagnosis and ap-proaches to treatment with reference to the literature.

  3. Acinar Cell Cyst adenoma (Acinar Cystic Transformation) of the Pancreas: the Radiologic-Pathologic Features

    Energy Technology Data Exchange (ETDEWEB)

    Gumus, Mehmet; Algin, Oktay; Gundogdu, Haldun [Ataturk Training and Research Hospital, Ankara (Turkmenistan); Ugras, Serdar [Selcuk University, Selcuklu Medical Faculty, Konya (Turkmenistan)

    2011-02-15

    Acinar cystic transformation of the pancreas is also known as acinar cell cystadenoma (ACC), and this is an extremely rare benign lesion that was first described in April 2002. We report here on a case of a previously asymptomatic patient with pancreatic ACC and this was diagnosed by computed tomography (CT) and magnetic resonance imaging (MRI). To the best of our knowledge, there is no previous report concerning the CT or MRI features of ACC in the medical literature. We present here the CT, MRI and pathological findings of pancreatic ACC

  4. Nonenzymatic cryogenic isolation of therapeutic cells: novel approach for enzyme-free isolation of pancreatic islets using in situ cryopreservation of islets and concurrent selective freeze destruction of acinar tissue.

    Science.gov (United States)

    Taylor, Michael J; Baicu, Simona C

    2014-01-01

    Cell-based therapies, which all involve processes for procurement and reimplantation of living cells, currently rely upon expensive, inconsistent, and even toxic enzyme digestion processes. A prime example is the preparation of isolated pancreatic islets for the treatment of type 1 diabetes by transplantation. To avoid the inherent pitfalls of these enzymatic methods, we have conceptualized an alternative approach based on the hypothesis that cryobiological techniques can be used for differential freeze destruction of the pancreas (Px) to release islets that are selectively cryopreserved in situ. Pancreata were procured from juvenile pigs using approved procedures. The concept of cryoisolation is based on differential processing of the pancreas in five stages: 1) infiltrating islets in situ preferentially with a cryoprotectant (CPA) cocktail via antegrade perfusion of the major arteries; 2) retrograde ductal infusion of water to distend the acinar; 3) freezing the entire Px solid to dithizone for identification of intact islets and with Syto 13/PI for fluorescence viability testing and glucose-stimulated insulin release assessment. As predicted, the cryoisolate contained small fragments of residual tissue comprising an amorphous mass of acinar tissue with largely intact and viable (>90%) embedded islets. Islets were typically larger (range 50-500 µm diameter) than their counterparts isolated from juvenile pigs using conventional enzyme digestion techniques. Functionally, the islets from replicate cryoisolates responded to a glucose challenge with a mean stimulation index = 3.3 ± 0.7. An enzyme-free method of islet isolation relying on in situ cryopreservation of islets with simultaneous freeze destruction of acinar tissue is feasible and proposed as a new and novel method that avoids the problems associated with conventional collagenase digestion methods. PMID:23992741

  5. Gemcitabine Hydrochloride With or Without Erlotinib Hydrochloride Followed By the Same Chemotherapy Regimen With or Without Radiation Therapy and Capecitabine or Fluorouracil in Treating Patients With Pancreatic Cancer That Has Been Removed By Surgery

    Science.gov (United States)

    2016-10-19

    Pancreatic Acinar Cell Carcinoma; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraductal Papillary-Mucinous Neoplasm; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer

  6. The natural history of pancreatic acinar cell cystadenoma: Is resection better than surveillance? An update to a case report from 2010

    OpenAIRE

    Darcy, David G.; Dominique Jan

    2016-01-01

    Cystic lesions of the pancreas are a rare entity, and few reports have described their natural history in children. A previously published report described a 9-year-old boy with an acinar cell cystadenoma, discovered during a laparoscopic appendectomy. Initially asymptomatic and followed by serial MRI, this patient presented to our institution several years later with chronic obstructive symptoms that required surgical intervention. Planning for resection included multidisciplinary input from...

  7. High Volume Washing of the Abdomen in Increasing Survival After Surgery in Patients With Pancreatic Cancer That Can Be Removed by Surgery

    Science.gov (United States)

    2016-05-03

    Acinar Cell Carcinoma; Ampulla of Vater Adenocarcinoma; Cholangiocarcinoma; Duodenal Adenocarcinoma; Pancreatic Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; Pancreatic Intraductal Papillary Mucinous Neoplasm, Pancreatobiliary-Type; Periampullary Adenocarcinoma

  8. Research of TAP Induction The Pancreatic Acinar Cells to Release HMGB1 in Rat%TAP诱导大鼠胰腺腺泡细胞释放HMGB1的研究

    Institute of Scientific and Technical Information of China (English)

    王国良; 兑丹华; 白亮; 刘尧; 田飞; 魏巍

    2012-01-01

    目的 探讨人胰蛋白酶原激活肽(TAP)诱导大鼠胰腺腺泡细胞高迁移率族蛋白1(HMGB1)的分泌规律和丙酮酸乙酯(EP)对其释放的影响.方法 将12只SD大鼠处死后,取出胰腺分离胰腺腺泡细胞,将所得细胞悬液按抽签法随机分为3组,对照组、TAP组及EP组.TAP组及EP组加入相同剂量的TAP(终浓度3 nmol/L),EP组同时加入EP(终浓度28 mmol/L),在3、6、12及24 h分别取细胞样本.采用实时定量逆转录聚合酶链反应(RT-PCR)检测HMGB1 mRNA的表达,蛋白印迹法(Western blot)检测HMGB1蛋白的表达;并进行HMGB1 mRNA及蛋白的表达与TAP作用时间的Spearman秩相关分析.结果 与对照组比较,TAP组及EP组的HMGB1 mRNA及蛋白的表达均随TAP作用时间的延长而上调(P<0.05);与TAP组比较,EP组的HMGB1mRNA及蛋白表达则下调(P<0.05).TAP组组内比较显示,HMGB1 mRNA及蛋白的表达随TAP作用时间延长而逐渐升高(P<0.05),且以12h及24 h时升高明显(P<0.01),HMGB1 mRNA及蛋白的表达与TAP作用时间呈正相关(rs=0.971,P<0.01;rs=0.966,P<0.01).结论 TAP可诱导大鼠胰腺腺泡细胞内HMGB1的释放.急性胰腺炎早期的TAP与晚期的HMGB1之间存在着时间的正向联系.EP可抑制HMGB1的释放.%Objective To explore the secretion law of high mobility group box 1 (HMGB1) in rat pancreatic acinar cells induced by trypsin activation peptide (TAP) and release of HMGB1 affected by ethyl pyruvate (EP) . Methods The experiment was performed in 12 SD rats. The pancreatic acinar cells of rats were taken out and then separated into three groups: control group, TAP group, and EP group. TAP was added into TAP group and EP group (keep TAP at a final concentration of 3 nmol/L), respectively, but EP was added into EP group only (keep EP at a final concentration of 28 mmol/L). The expressions of HMGB1 mRNA and protein were detected by using real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) or

  9. Impact of PI3Kγ gene knockout on acinar cells in mice with acute pancreatitis%磷脂酰肌醇3-激酶γ基因敲除对急性胰腺炎小鼠腺泡细胞的影响

    Institute of Scientific and Technical Information of China (English)

    贾文焯; 孙建华; 余涛; 肖刚

    2012-01-01

    目的:探讨磷脂酰肌醇3-激酶γ(PI3Kγ)基因敲除对急性胰腺炎(AP)小鼠病变程度、腺泡细胞功能以及对HSP70表达的影响.方法:雄性野生型( WT) C57BL/6小鼠和雄性PI3Kγ基因敲除(KO)小鼠各12只,随机均分为对照组和AP组,采用腹腔内注射蛙皮素诱导在体AP模型,对照组以同样的方式和体积给予生理盐水;另取两种动物各8只,行胰腺腺泡细胞体外分离,用胆囊收缩素(CCK-8)刺激作为离体AP模型,对照组给予二甲基亚砜(DMSO).观察胰腺组织病理变化、血清淀粉酶水平、胰腺组织和腺泡细胞胰蛋白酶活性和腺泡细胞淀粉酶释放率.Western blot检测胰腺组织及腺泡细胞中HSP70蛋白的表达.结果:病理学观察,两种小鼠的对照组胰腺未见异常,而AP组均出现不同程度的水肿、出血、坏死,经定量分析,KO小鼠胰腺炎腺泡细胞坏死数量和空泡数量明显少于WT小鼠(均P<0.05);两对照组间胰腺组织胰蛋白酶活性和体外腺泡细胞胰蛋白酶活性无明显差异(均P>0.05),但AP组(在体、离体)KO小鼠胰腺组织及腺泡的胰蛋白酶活性均低于WT小鼠(均P<0.05).两种小鼠间血清淀粉酶水平及腺泡细胞淀粉酶释放曲线差异无统计学意义(P>0.05);与对照组比较,AP组(在体、离体)小鼠胰腺组织和腺泡细胞HSP70表达均增加,且KO小鼠表达量明显大于WT小鼠(均P<0.05).结论:AP时,PI3Kγ可能通过下调HSP70表达水平和增强胰蛋白酶原活化促进腺泡细胞坏死,而对淀粉酶的分泌过程无明显影响.%Objective: To observe the effect of PI3Kγ gene knockout on the extent of the pancreatic lesion, acinar cellfunction and HSP70 protein expression level of mice with acute pancreatitis (AP).Methods: The male wild-type (WT) C57BL/6 mice and PI3Kγ gene knockout (KO) mice were randomly divided into control group and AP group with 12 mice in each group. The in vivo AP model was induced by intraperitoneal

  10. 姜黄素对长期摄入酒精和不同量蛋白质的大鼠胰腺腺泡细胞损伤的保护作用研究%Effects of Curcumin on Pancreatic Acinar Cell Injury in Rats with Long-term Alcohol Intake and Different Amount of Protein

    Institute of Scientific and Technical Information of China (English)

    周旭春

    2011-01-01

    目的:研究姜黄素对长期摄入酒精和不同量蛋白质的大鼠胰腺腺泡细胞损伤的保护作用.方法:实验分为5组,即正常对照(正常饲养)、高蛋白、低蛋白、高蛋白+姜黄素、低蛋白+姜黄素(以25%酒精代替饮水自由饮用,高、低蛋白质占总热量供给的32%、6%,喂饲6个月)组.在光镜和电镜下观察大鼠胰腺腺泡细胞结构变化,用比色法检测胰腺组织匀浆淀粉酶和脂肪酶的含量,TUNEL法检测腺泡细胞凋亡情况,免疫组化检测胰腺组织切片中环氧化酶-2(COX-2)的变化.结果:与高、低蛋白组比较,高、低蛋白+姜黄素组大鼠胰腺腺泡细胞髓样结构减少,线粒体肿胀减轻;淀粉酶和脂肪酶含量均显著升高(P<0.05);胰腺腺泡细胞凋亡显著减少(P<0.05);COX-2的表达降低.结论:姜黄素可预防摄入酒精联合过高或过低蛋白质的大鼠胰腺腺泡细胞损伤,延缓酒精性胰腺损伤的进程.%OBJECTIVE: To investigate the protective effects of curcumin on pancreatic acinar cell injury in rats with long-term alcohol intake and protein consumption. METHODS: Wistar rats were divided into 5 groups, I.e. Normal control group (the group fed with normal feed) ,high protein group, low protein group, high protein+curcumin group, low protein+curcumin group (those groups fed with diet containing 25% ethanol instead of drinking water for 6 months). High and low protein accounted for 32% and 6 % of total heat quantity. The structure change of pancreatic acinar cell was observed under light microscope and electron microscope. The contents of amylase and lipase in pancreatic tissue homogenate were determined by colorimetry. Apoptosis and expression of cyclooxygenase-2(COX-2) in acinar cell were detected by TUNEL and immunohistochemical staining, respectively. RESULTS: Compared with no application of curcumin, myelin figure and enlarged mitochondria were reduced in curcumin treatment groups. Lipase and amylase

  11. What is the origin of pancreatic adenocarcinoma?

    Directory of Open Access Journals (Sweden)

    Pandey Krishan K

    2003-01-01

    Full Text Available Abstract The concept of pancreatic cancer origin is controversial. Acinar, ductal or islet cells have been hypothesized as the cell of origin. The pros and cons of each of these hypotheses are discussed. Based on the world literature and recent observations, pancreatic cells seem to have potential for phenotypical transdifferentiation, i.e ductal-islet, ductal-acinar, acinar-ductal, acinar-islet, islet-acinar and islet-ductal cells. Although the possibility is discussed that cancer may arise from either islet, ductal or acinar cells, the circumstances favoring the islet cells as the tumor cell origin include their greater transdifferentiation potency into both pancreatic and extrapancreatic cells, the presence of a variety of carcinogen-metabolizing enzymes, some of which are present exclusively in islet cells and the growth factor-rich environment of islets.

  12. Pancreatitis

    Science.gov (United States)

    ... the hormones insulin and glucagon into the bloodstream. Pancreatitis is inflammation of the pancreas. It happens when digestive enzymes start digesting the pancreas itself. Pancreatitis can be acute or chronic. Either form is ...

  13. Pancreatitis

    Institute of Scientific and Technical Information of China (English)

    1997-01-01

    970359 CT diagnosis of pancreatic carcinoma andchronic pancreatitis. LUAN Baoqing(栾宝庆), et al,Dept Radiol, Beijing Friendship Hosp, Capital Med U-niv, Beijing, 100050. Chin J Radiol 1997; 31(2): 114-118. Objective: To improve the diagnostic accuracy ofpancreatic carcinoma and chronic pancreatitis. Materi-

  14. Pancreatitis

    Institute of Scientific and Technical Information of China (English)

    1995-01-01

    950347 Pancreatic endorcine response to parenteralnutrition in experimental acute pancreatitis.SUN Xi-aoguang(孙晓光),et al.Dept Nucl Med,ZhongshanHosp,Shanghai Med Univ,Shanghai.Shanghai Med J1995;18(2),74-70.In order to study the pancreatic endocrine responseto parenteral nutrition (PN) in acute pancreatitis,thedisease was induced in dogs by injecting 4% tauro-cholate sodium 0.5ml/kg plus trypsin 0.5mg/kg into the pancreatic duct.Intravenous infusion of PN wasinitiated one hour after the establishment of the dis-

  15. Pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010355 Oxymatrine enhances the expression of collagen I and α-SMA in rat chronic pancreatitis. WANG Yuliang(王昱良),et al. Dept Gastroenterol ,Huanghe Hosp,Sanmenxia 472000. World Chin J Digestol 2010;18(13):1331-36. Objective To investigate the treatment effects of oxymatrine (OM) against chronic pancreatitis in rats and to explore the potential

  16. PTD-NBD polypeptide down-regulates expression of NF-κB p65 in inflammatory pancreatic acinar cell injury in rats%PTD-NBD多肽对大鼠胰腺腺泡细胞炎症损伤中NF-κB表达的影响

    Institute of Scientific and Technical Information of China (English)

    谢文瑞; 杨元生; 杨新魁; 陈垦; 陈婧华; 崔淑兰; 王晖

    2013-01-01

    To examine the effect of PTD-NBD polypeptide on the expression of nuclear factor κB (NF-κB) p65 in inflammatory pancreatic acinar cell injury in rats.METHODS:Rat pancreatic acinar cells were isolated,cultured,and divided into a normal control group,an acute pancreatitis (AP) group and a PTD-NBD polypeptides group.An in vitro model of AP was induced by treating rat pancreatic acinar cells with lipopolysaccharide (10 mg/L).Cell morphological changes were observed,and the contents of amylase,superoxide dismutase (SOD) and IL-1β in culture medium were tested.Expression of NF-κB p65 mRNA and protein in cells was detected by RT-PCR and Western blot 6 and 12 h after modeling,respectively.RESULTS:Compared to the control group,pancreatic acinar cell swelling and death were increased (6 h:8.9 ± 0.34 vs 1.1 ± 0.13; 12 h:9.4 ± 0.26 vs 1.2 ± 0.15,both P < 0.05),the contents of amylase (6 h:2135.8 ± 347.2 vs 873.5 ± 91.6; 12 h:3299.6 ± 217.7 vs 917.7 ± 101.9,both P < 0.05) and IL-1β (6 h:84.9 ± 15.7 vs 39.3 ± 7.9; 12 h:95.6 ± 17.1 vs 38.9 ± 5.2,both P < 0.05) were increased and the contents of SOD were decreased in culture medium (6 h:116.3 ± 30.3 vs 176.2 ± 21.6; 12h:101.5 ± 25.6 vs 173.6 ± 27.9,P < 0.05),and the expression of NF-kB p65 in pancreatic acinar ceils was increased (P < 0.05) in the AP group at 6 and 12 h after modeling.Compared to the AP group,pancreatic acinar cell swelling and death were lessened (6 h:6.8 ± 0.23 vs 8.9 ± 0.34; 12 h:7.5 ± 0.19 vs 9.4 ± 0.26,both P < 0.05),the contents of SOD were raised (6 h:137.6 ± 27.4 vs 116.3 ± 30.3; 12 h:144.3 ± 23.6 vs 101.5 ± 25.6,both P < 0.05)and the contents of amylase (6 h:1951.5 ± 211.7 vs 2135.8 ± 347.2; 12 h:1761.3 ± 231.5 vs 3299.6 ± 217.7,both P < 0.05) and IL-1β (6 h:66.8 ± 11.6 vs 84.9 ± 15.7; 12 h:54.8 ± 21.2 vs 95.6 ± 17.1,both P < 0.05) were decreased in culture medium,and the expression of NF-κB p65 mRNA and protein was down-regulated in the PAT

  17. Pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    2008318 Proteomics of hyperlipidemia-associated pancreatitis using differential gel electrophoresis and tandem mass spectrometry: experiment with rats. ZHANG Wei(张伟), et al. Dept Gastroenterol, Shanghai 1st Hosp, Shanghai Jiaotong Univ, Shanghai 200080. Natl Med J China 2008;88(16):1132-1131.Objective To analyze the injury mechanismof hyperlipidemia-associated acute pancreatitis utilizing pro-teomics.Methods Ten SD rats were fed with high fat feed to establish hyperlipidemic models,and 10 SD rats were fed with normal feed to be used as control group.

  18. Acinar Cell Carcinoma of the Pancreas: A Possible Role of S-1 as Chemotherapy for Acinar Cell Carcinoma. A Case Report

    Directory of Open Access Journals (Sweden)

    Tameyoshi Yamamoto

    2012-01-01

    Full Text Available Context Acinar cell carcinoma of the pancreas is a rare malignancy, accounting for 1-2% of pancreatic exocrine malignancies. This rarity makes it difficult to standardize a protocol of treatment for acinar cell carcinoma. Case report A 71-year-old male without any particular past history was referred to our institute with abdominal distention and mild liver dysfunction. Computed tomography (CT revealed a cystic lesion with a diameter of 3.5 cm, which originated from the neck of pancreas and had solid nodules inside. Several nodules were demonstrated surrounding the cystic tumor. Laparotomy and histological study demonstrated peritoneal dissemination of acinar cell carcinoma. The patient was treated with S-1 monotherapy (80 mg/m2 for four weeks with a two-week interval as one cycle. After one cycle of S-1 monotherapy, CT demonstrated remarkable shrinkage of the main tumor and disappearance of the nodules on the peritoneum. The patient underwent a radical distal pancreatectomy. The patient was then treated with 16 cycles of S-1 monotherapy after the radical pancreatectomy and remains without any recurrence of the disease two years later. Conclusion Initially inoperable acinar cell carcinoma was treated by monotherapy using S-1, resulting in curative operation and two years disease free survival post operation. S-1 might be more effective on acinar cell carcinoma, rather than gemcitabine

  19. 糖尿病/星型胶质细胞富集磷蛋白酶-15的表达对急性胰腺炎腺泡细胞凋亡的影响%Effects of diabetes mellitus/astrocyte enriched phosphorus protease 15 expression on the apoptosis of acinar cells in acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    胡明星; 王玉柱; 刘传江; 秦涛

    2015-01-01

    目的 观察糖尿病/星型胶质细胞富集磷蛋白酶-15(PED/PEA-15)的表达对蛙皮素诱导的体外急性胰腺炎(AP)模型腺泡细胞凋亡的影响.方法 建立体外AP模型:用10 nmol/L的蛙皮素处理胰腺腺泡细胞株(AR42J细胞)建立AP模型,4h后检测培养液淀粉酶水平,实时荧光定量反转录聚合酶链反应(RT-PCR)检测PED/PEA-15的mRNA表达,吖啶橙/溴乙锭(AO/EB)法检测AR42J细胞的凋亡.构建PED/PEA-15的真核表达载体pcDNA3和空载体,利用脂质体转染AR42J细胞,72 h后加入10 nmol/L的蛙皮素处理,RT-PCR检测PED/PEA-15的mRNA表达水平,AO/EB法检测AR42J细胞的凋亡.结果 蛙皮素处理的AR42J细胞培养液淀粉酶水平较未处理细胞明显升高[(748.75±42.90) U/L较(249.75±27.16) U/L,P<0.05],PED/PEA-15的mRNA表达降低(5.24±0.66)倍(P<0.05),细胞凋亡率[(78.75±0.03)%]较未处理组[(17.50±0.04)%]升高(P<0.05).PED/PEA-15-pcDNA组AR42J细胞较空载体组PED/PEA-15的mRNA表达升高(4.27±0.78)倍(P<0.05),淀粉酶水平[(528.71±34.92) U/L]较空载体组[(856.29±52.39) U/L]明显下降(P<0.05),细胞凋亡率[(22.19±1.21)%]较空载体组[(68.92±1.83)%]降低(P<0.05),转染空载体组各项指标与未转染组差异无统计学意义(P>0.05).结论 PED/PEA-15蛋白在胰腺腺泡细胞的表达升高,能够抑制蛙皮素诱导的AR42J胰腺腺泡细胞凋亡.%Objective To investigate the effect of diabetes mellitus/astrocyte enriched phosphorus protease 15 (PED/PEA-15) expression on the apoptosis of acinar cells in bombesin-induced acute pancreatitis.Methods A model of acute pancreatitis with bombesin of 10 nmol/L was established.Amylase was determined 4 h later.The real-time reverse transcription polymerase chain reaction (RT-PCR) was used to detect the expression of PED/PEA-15 mRNA.The pcDNA or empty vehicle was created and transfected into AR42J cells.After the AR42J cells were treated with 10 nmol/L bombesin for 72 h, the

  20. Dynamic Contrast Enhanced MRI in Patients With Advanced Breast or Pancreatic Cancer With Metastases to the Liver or Lung

    Science.gov (United States)

    2014-05-28

    Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Liver Metastases; Lung Metastases; Recurrent Breast Cancer; Recurrent Pancreatic Cancer; Stage IV Breast Cancer; Stage IV Pancreatic Cancer

  1. Cytotoxic effect of desoxycholic acid on pancreatic acinar cells and its influence on the activity of nuclear transcription factors%脱氧胆酸对胰腺腺泡细胞的损伤及核转录因子活性的影响

    Institute of Scientific and Technical Information of China (English)

    张桂信; 陈海龙; 曹传海; 林小洋; 张利; 纪军; 王永鹏

    2011-01-01

    目的 观察脱氧胆酸(DCA)对AR42J胰腺腺泡细胞的损伤作用并探讨其对核转录因子(TF)活性的影响。方法 应用噻唑蓝(MTT)比色法检测DCA作用下细胞存活率改变,流式细胞术AV/PI双染法检测细胞的凋亡/坏死率。细胞经0.4mmoL/L DCA分别作用15 min、30 min、4h后收集培液上清,收集细胞并提取细胞质和细胞核蛋白,分别检测培液上清和胞质淀粉酶的活性,利用Luminex检测细胞核TF的DNA结合活性。结果 DCA对AR42J胰腺腺泡细胞的损伤作用呈浓度和时间依赖性,对细胞质内和培液中的淀粉酶水平无明显影响。在检测的40种TF活性变化中,DCA诱导ATF2、AR33、STAT5、NFAT、FKHR和NKX-2.5这6种TF活性明显升高,而RUNX/AML、NF-Y、MEF2和E2F1这4种TF活性则明显下降,其余30种TF活性无明显变化。结论 DCA对腺泡细胞的损伤作用主要表现为凋亡和坏死,对细胞内酶的合成和分泌功能没有明显影响。DCA诱导细胞核TF活性的变化,可能是其诱导细胞损伤的分子生物学基础。%Objective To study the cytotoxic effect of desoxycholic acid (DCA) on pancreatic acinar cells AR42J, its impact on the synthesis and secretion function of amylase, and the influence on the activity of nuclear transcription factor (TF). MethodsThe cytotoxic effect of DCS was detected in rat AR42J cells by using methyl thiazol tetrazolium (MTT) assay. The rate of apoptosis or necrosis was determined by flow cytometry. After the cells were incubated with DCA (0. 4 mmol/L) for 15 min, 30 min, or 4 h, the medium was collected to detect the activity of amylase. The cytoplamic protein was extracted to detect the activity of amylase, and nuclear protein was extracted to detect the DNA binding activity of 40 TFs by Luminex. Results DCA exerted cytotoxic effects on AR42J cells in a time-and dose-dependent manner, and induced cell apoptosis and necrosis. DCA had no significant influence on the amylase synthesis and secretion

  2. Molecular mechanisms of alcohol associated pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Dahn; L; Clemens; Mark; A; Wells; Katrina; J; Schneider; Shailender; Singh

    2014-01-01

    Alcohol abuse is commonly associated with the development of both acute and chronic pancreatitis. Despite this close association, the fact that only a small percentage of human beings who abuse alcohol develop pancreatitis indicates that alcohol abuse alone is not sufficient to initiate clinical pancreatitis. This contention is further supported by the fact that administration of ethanol to experimental animals does not cause pancreatitis. Because of these findings, it is widely believed that ethanol sensitizes the pancreas to injury and additional factors trigger the development of overt pancreatitis. How ethanol sensitizes the pancreas to pancreatitis is not entirely known. Numerous studies have demonstrated that ethanol and its metabolites have a number of deleterious effects on acinar cells. Important acinar cells properties that are affected by ethanol include: calcium signaling, secretion of zymogens, autophagy, cellular regeneration, the unfolded protein response, and mitochondrial membrane integrity. In addition to the actions of ethanol on acinar cells, it is apparent that ethanol also affects pancreatic stellatecells. Pancreatic stellate cells have a critical role in normal tissue repair and the pathologic fibrotic response. Given that ethanol and its metabolites affect so many pancreatic functions, and that all of these effects occur simultaneously, it is likely that none of these effects is "THE" effect. Instead, it is most likely that the cumulative effect of ethanol on the pancreas predisposes the organ to pancreatitis. The focus of this article is to highlight some of the important mechanisms by which ethanol alters pancreatic functions and may predispose the pancreas to disease.

  3. Ethanol consumption as inductor of pancreatitis

    Institute of Scientific and Technical Information of China (English)

    José; A; Tapia; Ginés; M; Salido; Antonio; González

    2010-01-01

    Alcohol abuse is a major cause of pancreatitis, a condition that can manifest as both acute necroinflammation and chronic damage (acinar atrophy and f ibrosis). Pancreatic acinar cells can metabolize ethanol via the oxidative pathway, which generates acetaldehyde and involves the enzymes alcohol dehydrogenase and possibly cytochrome P4502E1. Additionally, ethanol can be metabolized via a nonoxidative pathway involving fatty acid ethyl ester synthases. Metabolism of ethanol by acinar and other pancreatic cells and the consequent generation of toxic metabolites, are postulated to play an important role in the development of alcohol-related acute and chronic pancreatic injury. This current work will review some recent advances in the knowledge about ethanol actions on the exocrine pancreas and its relationship to inflammatory disease and cancer.

  4. Alteraciones fisiopatológicas tempranas asociadas a pancreatitis crónica en células acinares pancreáticas: mecanismos de respuesta frente a tóxicos

    OpenAIRE

    Luaces Regueira, María

    2013-01-01

    La pancreatitis crónica, una de las enfermedades del páncreas con mayor prevalencia, se caracteriza por un infiltrado inflamatorio crónico que puede conllevar la pérdida de las funciones exocrina y endocrina de la glándula y que constituye el principal factor de riesgo conocido, junto con el tabaco y la diabetes, para el desarrollo del cáncer de páncreas. Se describieron diferentes factores etiológicos capaces de desencadenar, tanto aislados como en asociación, este proceso pat...

  5. Beer and its Non-Alcoholic Compounds: Role in Pancreatic Exocrine Secretion, Alcoholic Pancreatitis and Pancreatic Carcinoma

    Directory of Open Access Journals (Sweden)

    Peter Feick

    2010-03-01

    Full Text Available : In this article we provide an overview of the newest data concerning the effect of non-alcoholic constituents of alcoholic beverages, especially of beer, on pancreatic secretion, and their possible role in alcoholic pancreatitis and pancreatic carcinoma. The data indicate that non-alcoholic constituents of beer stimulate pancreatic enzyme secretion in humans and rats, at least in part, by direct action on pancreatic acinar cells. Some non-alcoholic compounds of beer, such as quercetin, resveratrol, ellagic acid or catechins, have been shown to be protective against experimentally induced pancreatitis by inhibiting pancreatic secretion, stellate cell activation or by reducing oxidative stress. Quercetin, ellagic acid and resveratrol also show anti-carcinogenic potential in vitro and in vivo. However, beer contains many more non-alcoholic ingredients. Their relevance in beer-induced functional alterations of pancreatic cells leading to pancreatitis and pancreatic cancer in humans needs to be further evaluated.

  6. Cerulein Pancreatitis: Oxidative Stress, Inflammation, and Apoptosis

    OpenAIRE

    Kim, Hyeyoung

    2008-01-01

    Cerulein pancreatitis is similar to human edematous pancreatitis, manifesting with dysregulation of digestive enzyme production and cytoplasmic vacuolization, the death of acinar cells, edema formation, and infiltration of inflammatory cells into the pancreas. Reactive oxygen species are involved in nuclear factor-κB activation, cytokine expression, apoptosis and pathogenesis of pancreatitis. There is recent evidence that cerulein activates NADPH oxidase, which is a major source of reactive o...

  7. Acinar Cell Carcinoma of the Pancreas with Colon Involvement

    Directory of Open Access Journals (Sweden)

    Naoki Asayama

    2014-01-01

    Full Text Available We report a case of acinar cell carcinoma of the pancreas with colon involvement that was difficult to distinguish from primary colon cancer. A 60-year-old man was admitted with a 1-month history of diarrhea. Contrast-enhanced computed tomography (CT revealed a large tumor (10.6×11.6 cm at the splenic flexure of the colon. Colonoscopy showed completely round ulcerative lesions, and biopsy revealed poorly differentiated adenocarcinoma. Left hemicolectomy, resection of the jejunum and pancreas body and tail, and splenectomy were performed based on a diagnosis of descending colon cancer (cT4N0M0, stage IIB, and surgery was considered to be curative. Diagnosis was subsequently confirmed as moderately differentiated acinar cell carcinoma of the pancreas by immunohistochemical staining (pT3N0M0, stage IIA. Multiple liver metastases with portal thrombosis were found 8 weeks postoperatively. Despite combination chemotherapy with oral S-1 and gemcitabine, the patient died of hepatic failure with no effect of chemotherapy 14 weeks postoperatively. Correct diagnosis was difficult to determine preoperatively from the clinical, CT, and colonoscopy findings. Moreover, the disease was extremely aggressive even after curative resection. Physicians should consider pancreatic cancer in the differential diagnosis of similar cases.

  8. Whole exome sequencing reveals recurrent mutations in BRCA2 and FAT genes in acinar cell carcinomas of the pancreas

    OpenAIRE

    Toru Furukawa; Hitomi Sakamoto; Shoko Takeuchi; Mitra Ameri; Yuko Kuboki; Toshiyuki Yamamoto; Takashi Hatori; Masakazu Yamamoto; Masanori Sugiyama; Nobuyuki Ohike; Hiroshi Yamaguchi; Michio Shimizu; Noriyuki Shibata; Kyoko Shimizu; Keiko Shiratori

    2015-01-01

    Acinar cell carcinoma of the pancreas is a rare tumor with a poor prognosis. Compared to pancreatic ductal adenocarcinoma, its molecular features are poorly known. We studied a total of 11 acinar cell carcinomas, including 3 by exome and 4 by target sequencing. Exome sequencing revealed 65 nonsynonymous mutations and 22 indels with a mutation rate of 3.4 mutations/Mb per tumor, on average. By accounting for not only somatic but also germline mutations with loss of the wild-type allele, we ide...

  9. Acute pancreatitis: Etiology and common pathogenesis

    Institute of Scientific and Technical Information of China (English)

    Guo-Jun Wang; Chun-Fang Gao; Dong Wei; Cun Wang; Si-Qin Ding

    2009-01-01

    Acute pancreatitis is an inflammatory disease of the pancreas. The etiology and pathogenesis of acute pancreatitis have been intensively investigated for centuries worldwide. Many causes of acute pancreatitis have been discovered, but the pathogenetic theories are controversial. The most common cause of acute pancreatitis is gallstone impacting the distal common bile-pancreatic duct. The majority of investigators accept that the main factors for acute billiary pancreatitis are pancreatic hyperstimulation and bile-pancreatic duct obstruction which increase pancreatic duct pressure and active trypsin reflux. Acute pancreatitis occurs when intracellular protective mechanisms to prevent trypsinogen activation or reduce trypsin activity are overwhelmed. However, little is known about the other acute pancreatitis. We hypothesize that acute biliary pancreatitis and other causes of acute pancreatitis possess a common pathogenesis. Pancreatic hyperstimulation and pancreatic duct obstruction increase pancreatic duct pressure, active trypsin reflux, and subsequent unregulated activation of trypsin within pancreatic acinar cells. Enzyme activation within the pancreas leads to auto-digestion of the gland and local inflammation. Once the hypothesis is confirmed, traditional therapeutic strategies against acute pancreatitis may be improved. Decompression of pancreatic duct pressure should be advocated in the treatment of acute pancreatitits which may greatly improve its outcome.

  10. β-Cell regeneration through the transdifferentiation of pancreatic cells: Pancreatic progenitor cells in the pancreas.

    Science.gov (United States)

    Kim, Hyo-Sup; Lee, Moon-Kyu

    2016-05-01

    Pancreatic progenitor cell research has been in the spotlight, as these cells have the potential to replace pancreatic β-cells for the treatment of type 1 and 2 diabetic patients with the absence or reduction of pancreatic β-cells. During the past few decades, the successful treatment of diabetes through transplantation of the whole pancreas or isolated islets has nearly been achieved. However, novel sources of pancreatic islets or insulin-producing cells are required to provide sufficient amounts of donor tissues. To overcome this limitation, the use of pancreatic progenitor cells is gaining more attention. In particular, pancreatic exocrine cells, such as duct epithelial cells and acinar cells, are attractive candidates for β-cell regeneration because of their differentiation potential and pancreatic lineage characteristics. It has been assumed that β-cell neogenesis from pancreatic progenitor cells could occur in pancreatic ducts in the postnatal stage. Several studies have shown that insulin-producing cells can arise in the duct tissue of the adult pancreas. Acinar cells also might have the potential to differentiate into insulin-producing cells. The present review summarizes recent progress in research on the transdifferentiation of pancreatic exocrine cells into insulin-producing cells, especially duct and acinar cells. PMID:27330712

  11. Loss of Periostin Results in Impaired Regeneration and Pancreatic Atrophy after Cerulein-Induced Pancreatitis.

    Science.gov (United States)

    Hausmann, Simone; Regel, Ivonne; Steiger, Katja; Wagner, Nadine; Thorwirth, Manja; Schlitter, Anna M; Esposito, Irene; Michalski, Christoph W; Friess, Helmut; Kleeff, Jörg; Erkan, Mert

    2016-01-01

    The extracellular matrix molecule periostin (POSTN, encoded by POSTN), which is secreted by activated pancreatic stellate cells, has important functions in chronic pancreatitis and pancreatic cancer. However, the role of POSTN in acute pancreatitis and subsequent regeneration processes has not been addressed so far. We analyzed the function of POSTN in pancreatic exocrine regeneration after the induction of a severe acute pancreatitis. Postn-deficient mice and wild-type control animals received repetitive cerulein injections, and a detailed histologic analysis of pancreatic tissues was performed. Although there was no difference in pancreatitis severity in the acute inflammatory phase, the recovery of the exocrine pancreas was massively impaired in Postn-deficient mice. Loss of Postn expression was accompanied by strong pancreatic atrophy and acinar-to-adipocyte differentiation, which was also reflected in gene expression patterns. Our data suggest that POSTN is a crucial factor for proper exocrine lineage-specific regeneration after severe acute pancreatitis.

  12. Loss of Periostin Results in Impaired Regeneration and Pancreatic Atrophy after Cerulein-Induced Pancreatitis.

    Science.gov (United States)

    Hausmann, Simone; Regel, Ivonne; Steiger, Katja; Wagner, Nadine; Thorwirth, Manja; Schlitter, Anna M; Esposito, Irene; Michalski, Christoph W; Friess, Helmut; Kleeff, Jörg; Erkan, Mert

    2016-01-01

    The extracellular matrix molecule periostin (POSTN, encoded by POSTN), which is secreted by activated pancreatic stellate cells, has important functions in chronic pancreatitis and pancreatic cancer. However, the role of POSTN in acute pancreatitis and subsequent regeneration processes has not been addressed so far. We analyzed the function of POSTN in pancreatic exocrine regeneration after the induction of a severe acute pancreatitis. Postn-deficient mice and wild-type control animals received repetitive cerulein injections, and a detailed histologic analysis of pancreatic tissues was performed. Although there was no difference in pancreatitis severity in the acute inflammatory phase, the recovery of the exocrine pancreas was massively impaired in Postn-deficient mice. Loss of Postn expression was accompanied by strong pancreatic atrophy and acinar-to-adipocyte differentiation, which was also reflected in gene expression patterns. Our data suggest that POSTN is a crucial factor for proper exocrine lineage-specific regeneration after severe acute pancreatitis. PMID:26632158

  13. Protein kinase D regulates cell death pathways in experimental pancreatitis

    Directory of Open Access Journals (Sweden)

    Jingzhen eYuan

    2012-03-01

    Full Text Available Inflammation and acinar cell necrosis are two major pathological responses of acute pancreatitis, a serious disorder with no current therapies directed to its molecular pathogenesis. Serine/threonine protein kinase D family, which includes PKD/PKD1, PKD2, and PKD3, has been increasingly implicated in the regulation of multiple physiological and pathophysiological effects. We recently reported that PKD/PKD1, the predominant PKD isoform expressed in rat pancreatic acinar cells, mediates early events of pancreatitis including NF-kappaB activation and inappropriate intracellular digestive enzyme activation. In current studies, we investigated the role and mechanisms of PKD/PKD1 in the regulation of necrosis in pancreatic acinar cells by using two novel small molecule PKD inhibitors CID755673 and CRT0066101 and molecular approaches in in vitro and in vivo experimental models of acute pancreatitis. Our results demonstrated that both CID755673 and CRT0066101 are PKD-specific inhibitors and that PKD/PKD1 inhibition by either the chemical inhibitors or specific PKD/PKD1 siRNAs attenuated necrosis while promoting apoptosis induced by pathological doses of cholecystokinin-octapeptide (CCK in pancreatic acinar cells. Conversely, upregulation of PKD expression in pancreatic acinar cells increased necrosis and decreased apoptosis. We further showed that PKD/PKD1 regulated several key cell death signals including inhibitors of apoptotic proteins (IAPs, caspases, receptor-interacting protein kinase 1 (RIP1 to promote necrosis. PKD/PKD1 inhibition by CID755673 significantly ameliorated necrosis and severity of pancreatitis in an in vivo experimental model of acute pancreatitis. Thus, our studies indicate that PKD/PKD1 is a key mediator of necrosis in acute pancreatitis and that PKD/PKD1 may represent a potential therapeutic target in acute pancreatitis.

  14. Stress kinase inhibition modulates acute experimental pancreatitis

    Institute of Scientific and Technical Information of China (English)

    F. Fleischer; R. Dabew; B. Goke; ACC Wagner

    2001-01-01

    AIM To examine the role of p38 during acute experimental cerulein pancreatitis.METHODS Rats were treated with cerulein with or without a specific JNK inhibitor (CEP1347)andy or a specific p38 inhbitor (SB203380) and pancreatic stress kinase activity wasdetermined. Parameters to assess pancreatitis included trypsin, amylase, lipase, pancreatic weight and histology.RESULTS JNK inhibition with CEP1347ameliorated pancreatitis, reducing pancreatic edema. In contrast, p38 inhibition with SB203580aggravated pancreatitis with higher trypsinlevels and, with induction of acinar necrosis not normally found after cerulein hyperstimulation.Simultaneous treatment with both CEP1347 and SB203580 mutually abolished the effects of either compound on cerulein pancreatitis.CONCLUSION Stress kinases modulatepancreatitis differentially. JNK seems to promote pancreatitis development, possibly by supporting inflammatory reactions such as edema formation while its inhibition ameliorates pancreatitis. In contrast, p38 may help reduce organ destruction while inhibition of p38 during induction of cerulein pancreatitis leads to the occurrence of acinar necrosis.

  15. Overexpression of Caspase-1 in adenocarcinoma of pancreas and chronic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Yin-Mo Yang; Marco Ramadani; Yan-Ting Huang

    2003-01-01

    AIM: To identify the expression of Caspase-l(interleukin1.β converting enzyme) and its role in adenoma of the pancreas and chronic pancreatitis.METHODS: The expression of Caspase-1 was assessed in 42 pancreatic cancer tissue samples, 38 chronic pancreatitis specimens, and 9 normal pancreatic tissues by immunohistochemistry and Western blot analysis.RESULTS: Overexpression of Caspase-1 was observed in both disorders, but there were differences in the expression patterns in distinct morphologic compartments. Pancreatic cancer tissues showed a clear cytoplasmatic overexpression of Caspase-1 in tumor cells of 71% of the tumors, whereas normal pancreatic tissues showed only occasional immunoreactivity. In chronic pancreatitis, overexpression of Caspase-1 was found in atrophic acinar cells (89 %),hyperplastic ducts (87 %), and dedifferentiating acinar cells (84 %). Although in atrophic cells a clear nuclear expression was found, hyperplastic ducts and dedifferentiating acinar cells showed dear cytoplasmic expression. Western blot analysis revealed a marked expression of the 45 kDa precursor of Caspase-1 in pancreatic cancer and chronic pancreatitis (80 %and 86 %, respectively). Clear bands at 30 kDa, which suggested the p10-p20 heterodimer of active Caspase-1, were found in 60 % of the cancer tissue and 14 % of the pancreatitis tissue specimens, but not in normal pancreatic tissues.CONCLUSION: Overexpression of Caspase-1 is a frequent event in pancreatic disorders and its differential expression patterns may reflect two functions of the protease. One is its participation in the apoptotic pathway in atrophic acinar cells and tumor-surrounding pancreatitis tissue, the other is its possible role in proliferative processes in pancreatic cancer cells and hyperplastic duct cells and dedifferentiating acinar cells in chronic pancreatitis.

  16. Acinarcellcarcinomaofthepancreasina young patient with chronic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Fatima-Zahra Kebir; Ahlem Lahmar; Nafaa Arfa; Saber Manai; Mohamed Ali El Ouaer; Saadia Bouraoui; Carole Gouttalier; Sabah Mezabi-Regaya

    2010-01-01

    BACKGROUND: Acinar cell carcinoma (ACC) is a rare malignancy of the pancreas arising from acinar cells. Unlike ductal adenocarcinoma, this tumor rarely presents with pancreatitis. METHODS: We present a case of ACC associated with chronic calcifying pancreatitis, and a review of the literature focusing on diagnosis and management. RESULTS: A 43-year-old man was proposed for Wirsungo-jejunal derivation for chronic pancreatitis. Histopathological examination of the tissue extracted revealed an ACC. Duodenopancreatectomy was performed. Six months post-operatively, the patient developed hepatic metastasis and was treated with gemcitabine as palliative chemotherapy. CONCLUSIONS: The clinical presentation of ACC of the pancreas is not speciifc and the tumor can be under-diagnosed when associated with chronic pancreatitis. Data regarding course, treatment, and prognosis of this tumor are generally lacking.

  17. Ethacrynic acid inhibits pancreatic exocrine secretion%依他尼酸抑制胰腺外分泌

    Institute of Scientific and Technical Information of China (English)

    YU Hong-Gang; KLONOWSKI-STUMPE Hanne

    2001-01-01

    AIM: The effect of ethacrynic acid on pancreatic exocrine secretion function and potential mechanisms of interference with the secretory process in pancreatic acinar cells were investigated. METHODS: After incubation with ethacrynic acid for 30 min, caerulein-stimulated amylase release and cholecystokinin (CCK) receptor binding characteristics were assessed in isolated rat pancreatic acini. The level of thiol groups (glutathione and protein thiols ) and cytosolic free calcium were measured in pancreatic acinar cells. RESULTS:Ethacrynic acid decreased caerulein (0. 1 nmol/L )-stimulated amylase release and the level of pancreatic acinar glutathione in a concentration-dependent fashion without a marked increase in cell damage. Ethacrynic acid also inhibited the caerulein (1 nmol/L)-induced Ca2+ mobilization in pancreatic acinar cells. But neither protein thiol nor CCK-receptor binding characteristics was altered by ethacrynic acid. CONCLUSION: Ethacrynic acid inhibit pancreatic exocrine secretion by depletion of glutathione and down-regulation of caerulein-induced Ca2+ mobilization. Glutathione might play a potential role in the secretory process in pancreatic acinar cells and in the secretory blockade observed in acute pancreatitis.

  18. Pancreatic fibroblasts smoothen their activities via AKT-GLI2-TGFα.

    Science.gov (United States)

    Rustgi, Anil K

    2016-09-01

    Pancreatic stromal fibroblasts provide structural support. Activated fibroblasts are critical in the tumor microenvironment. In this issue of Genes & Development, Liu and colleagues (pp. 1943-1955) unravel the finding that depletion of Smoothened (Smo) in pancreatic stromal fibroblasts results in AKT activation and noncanonical GLI2 activation with subsequent TGFα secretion, activation of EGFR in pancreatic epithelial cells, and augmentation of acinar-ductal metaplasia. Additionally, Smo-mediated signaling has proproliferative effects on pancreatic tumor cells. PMID:27664234

  19. Effects of human interleukin 10 gene transfer on the expression of Bcl-2 Bax and apoptosis of hepatocyte in rats with acute hemorrhagic necrotizing pancreatitis

    Institute of Scientific and Technical Information of China (English)

    GU Jun-chao; WANG Yu; ZHANG Zhong-tao; XUE Jian-guo; LI Jian-she; ZHOU Yan-zhong

    2005-01-01

    @@ Acute necrotising pancreatitis is characterized by inflammatory and necrotic events, which follow the initial intra-acinar injury involving enzyme activation, and disruption of the acinar cytoskeleton.1 At present, apoptosis has become a hot topic in many kinds of disease.

  20. Chronic pancreatitis

    Science.gov (United States)

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

  1. Silencing Mist1 Gene Expression Is Essential for Recovery from Acute Pancreatitis.

    Directory of Open Access Journals (Sweden)

    Anju Karki

    Full Text Available Acinar cells of the exocrine pancreas are tasked with synthesizing, packaging and secreting vast quantities of pro-digestive enzymes to maintain proper metabolic homeostasis for the organism. Because the synthesis of high levels of hydrolases is potentially dangerous, the pancreas is prone to acute pancreatitis (AP, a disease that targets acinar cells, leading to acinar-ductal metaplasia (ADM, inflammation and fibrosis-events that can transition into the earliest stages of pancreatic ductal adenocarcinoma. Despite a wealth of information concerning the broad phenotype associated with pancreatitis, little is understood regarding specific transcriptional regulatory networks that are susceptible to AP and the role these networks play in acinar cell and exocrine pancreas responses. In this study, we examined the importance of the acinar-specific maturation transcription factor MIST1 to AP damage and organ recovery. Analysis of wild-type and Mist1 conditional null mice revealed that Mist1 gene transcription and protein accumulation were dramatically reduced as acinar cells underwent ADM alterations during AP episodes. To test if loss of MIST1 function was primarily responsible for the damaged status of the organ, mice harboring a Cre-inducible Mist1 transgene (iMist1 were utilized to determine if sustained MIST1 activity could alleviate AP damage responses. Unexpectedly, constitutive iMist1 expression during AP led to a dramatic increase in organ damage followed by acinar cell death. We conclude that the transient silencing of Mist1 expression is critical for acinar cells to survive an AP episode, providing cells an opportunity to suppress their secretory function and regenerate damaged cells. The importance of MIST1 to these events suggests that modulating key pancreas transcription networks could ease clinical symptoms in patients diagnosed with pancreatitis and pancreatic cancer.

  2. Effects of a diet high in fish oil (MaxEPA) on the formation of micronucleated erythrocytes in blood and on the number of atypical acinar cell foci induced in rat pancreas by Azaserine

    NARCIS (Netherlands)

    Appel, M.J.; Woutersen, R.A.

    2004-01-01

    The present study was performed to investigate the influence of fish oil on the genotoxic effects of azaserine, using the formation of micronucleated erythrocytes as a measure for the degree of initiating potency and the number and size of putative preneoplastic pancreatic atypical acinar cell foci

  3. Mixed acinar-neuroendocrine-ductal carcinoma of the pancreas: a tale of three lineages.

    Science.gov (United States)

    Anderson, Mark J; Kwong, Christina A; Atieh, Mohammed; Pappas, Sam G

    2016-01-01

    Most pancreatic cancers arise from a single cell type, although mixed pancreatic carcinomas represent a rare exception. The rarity of these aggressive malignancies and the limitations of fine-needle aspiration (FNA) pose significant barriers to diagnosis and appropriate management. We report a case of a 54-year-old man presenting with abdominal pain, jaundice and a hypodense lesion within the uncinate process on CT. FNA suggested poorly differentiated adenocarcinoma, which was subsequently resected via pancreaticoduodenectomy. Pathological analysis yielded diagnosis of invasive mixed acinar-neuroendocrine-ductal pancreatic carcinoma. Given the rare and deadly nature of these tumours, clinicians must be aware of their pathophysiology and do practice with a high degree of clinical suspicion, when appropriate. Surgical resection and thorough pathological analysis with immunohistochemical staining and electron microscopy remain the standards of care for mixed pancreatic tumours without gross evidence of metastasis. Diligent characterisation of the presentation and histological findings associated with these neoplasms should continue in order to promote optimal diagnostic and therapeutic strategies. PMID:27257019

  4. Pancreatic Stellate Cells and Chronic Alcoholic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Raffaele Pezzilli

    2007-03-01

    Full Text Available Chronic pancreatitis is a disease often characterized by recurrent episodes of abdominal pain accompanied by progressive pancreatic exocrine and endocrine insufficiency [1] and it sometimes requires multiple hospitalizations. Obstructive jaundice, duodenal stenosis, left-sided portal hypertension, pseudocyst and mass formation, and pancreatic carcinoma may occur as complications of chronic pancreatitis. The disease is frequently the result of chronic alcohol abuse, even if other factors such as genetic alterations, autoimmune disorders, and obstructive disease of the biliary tract and the pancreas may cause the disease [2]. Medical therapy is the treatment of choice for most patients and it is based on substitutive therapy for either exocrine or endocrine insufficiency and on analgesics for pain control. In the presence of intractable pain, surgical management is the main option [3] even if, in recent years, other therapeutic options such as endoscopic therapy [4], thoracoscopic splanchnicectomy [5], and extracorporeal shockwave lithotripsy have been applied in clinical practice [6]. From a pathological point of view, chronic pancreatitis is characterized by irregular sclerosis with destruction and loss of the exocrine parenchyma, and complete replacement of acinar, ductal and endocrine tissue by fibrotic tissue. It has recently been reported that acute alcoholic pancreatitis develops in a pancreas already affected by chronic pancreatitis [7]. In 1982, Watari et al. [8] reported the presence of vitamin A-containing cells in the vitamin A-fed rat pancreas. These were later described and characterized as stellate cells in the rat and the human pancreas [9, 10]. Pancreatic stellate cells are morphologically similar to hepatic stellate cells. They bear long cytoplasmic processes and are situated close to the pancreatic acini. In the quiescent state, these cells contain lipid droplets, store vitamin A and express markers such as desmin, glial

  5. Current concept of pathogenesis of severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Xie Ning Wu

    2000-01-01

    @@ The pathogenesis of severe acute pancreatitis is very complicated. It is a multifactorial as well as multifaceted disease. First of all, the etiologic agents initiate the pancreatic acinar injury by release of pancreatic enzymes and overstimulation of macrophages and neutrophils, then the cytokines and inflammatory mediators are liberated. There is also interaction between neutrophils and endothelial cells producing free radicals, the cytokines cause increasing vascular permeability, activating complement component, resulting in microcirculatory impairment and imbalance of thrombo-fibrinolytic system. Many of these events occur not only in the pancreas itself, but also in the other vital organs and tissues, leading to severe acute pancreatitis and complications. The sequencial events are as follows.

  6. Successful Salvage Chemotherapy with FOLFIRINOX for Recurrent Mixed Acinar Cell Carcinoma and Ductal Adenocarcinoma of the Pancreas in an Adolescent Patient.

    Science.gov (United States)

    Pfrommer, Sarah; Weber, Achim; Dutkowski, Philipp; Schäfer, Niklaus G; Müllhaupt, Beat; Bourquin, Jean-Pierre; Breitenstein, Stefan; Pestalozzi, Bernhard C; Stenner, Frank; Renner, Christoph; D'Addario, Giannicola; Graf, Hans-Jörg; Knuth, Alexander; Clavien, Pierre-Alain; Samaras, Panagiotis

    2013-01-01

    Pancreatic tumors are rare in children and adolescents. Here, we report the case of a 15-year-old boy who presented with a mixed acinar cell carcinoma/ductal adenocarcinoma with blastomatous components. He received multimodal treatment including various chemotherapy regimens and multistep surgery including liver transplantation. Introduction of FOLFIRINOX after relapse repeatedly achieved a durable metabolic and clinical response with good quality of life. PMID:24163668

  7. Successful Salvage Chemotherapy with FOLFIRINOX for Recurrent Mixed Acinar Cell Carcinoma and Ductal Adenocarcinoma of the Pancreas in an Adolescent Patient

    Directory of Open Access Journals (Sweden)

    Sarah Pfrommer

    2013-09-01

    Full Text Available Pancreatic tumors are rare in children and adolescents. Here, we report the case of a 15-year-old boy who presented with a mixed acinar cell carcinoma/ductal adenocarcinoma with blastomatous components. He received multimodal treatment including various chemotherapy regimens and multistep surgery including liver transplantation. Introduction of FOLFIRINOX after relapse repeatedly achieved a durable metabolic and clinical response with good quality of life.

  8. Intravenous Selenium Modulates L-Arginine-Induced Experimental Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Jonathan Hardman

    2005-09-01

    Full Text Available Context Oxidative stress is understood to have a critical role in the development of acinar injury in experimental acute pancreatitis. We have previously demonstrated that compound multiple antioxidant therapy ameliorates end-organ damage in the intra-peritoneal L-arginine rat model. As the principal co-factor for glutathione, selenium is a key constituent of multiple antioxidant preparations. Objective The intention of this study was to investigate the effect of selenium on pancreatic and remote organ injury in a wellvalidated experimental model of acute pancreatitis. Methods Male Sprague-Dawley rats were randomly allocated to one of 3 groups (n=5/group and sacrificed at 72 hours. Acute pancreatitis was induced by 250 mg per 100 g body weight of 20% L-arginine hydrochloride in 0.15 mol/L sodium chloride. Group allocations were: Group 1, control; Group 2, acute pancreatitis; Group 3, selenium. Main outcome measures Serum amylase, anti-oxidant levels, bronchoalveolar lavage protein, lung myeloperoxidase activity, and histological assessment of pancreatic injury. Results L-arginine induced acute pancreatitis characterised by oedema, neutrophil infiltration, acinar cell degranulation and elevated serum amylase. Selenium treatment was associated with reduced pancreatic oedema and inflammatory cell infiltration. Acinar degranulation and dilatation were completely absent. A reduction in bronchoalveolar lavage protein content was also demonstrated. Conclusion Intravenous selenium given 24 hours after induction of experimental acute pancreatitis was associated with a reduction in the histological stigmata of pancreatic injury and a dramatic reduction in broncho-alveolar lavage protein content. Serum selenium fell during the course of experimental acute pancreatitis and this effect was not reversed by exogenous selenium supplementation.

  9. Experimental evidence of obesity as a risk factor for severe acute pancreatitis

    OpenAIRE

    Frossard, Jean-Louis; Lescuyer, Pierre; Pastor, Catherine M

    2009-01-01

    The incidence of acute pancreatitis, an inflammation of the pancreas, is increasing worldwide. Pancreatic injury is mild in 80%-90% of patients who recover without complications. The remaining patients may develop a severe disease with local complications such as acinar cell necrosis, abscess and remote organ injury including lung injury. The early prediction of the severity of the disease is an important goal for physicians in management of patients with acute pancreatitis in order to optimi...

  10. A Microfluidic Model of Biomimetically Breathing Pulmonary Acinar Airways.

    Science.gov (United States)

    Fishler, Rami; Sznitman, Josué

    2016-01-01

    Quantifying respiratory flow characteristics in the pulmonary acinar depths and how they influence inhaled aerosol transport is critical towards optimizing drug inhalation techniques as well as predicting deposition patterns of potentially toxic airborne particles in the pulmonary alveoli. Here, soft-lithography techniques are used to fabricate complex acinar-like airway structures at the truthful anatomical length-scales that reproduce physiological acinar flow phenomena in an optically accessible system. The microfluidic device features 5 generations of bifurcating alveolated ducts with periodically expanding and contracting walls. Wall actuation is achieved by altering the pressure inside water-filled chambers surrounding the thin PDMS acinar channel walls both from the sides and the top of the device. In contrast to common multilayer microfluidic devices, where the stacking of several PDMS molds is required, a simple method is presented to fabricate the top chamber by embedding the barrel section of a syringe into the PDMS mold. This novel microfluidic setup delivers physiological breathing motions which in turn give rise to characteristic acinar air-flows. In the current study, micro particle image velocimetry (µPIV) with liquid suspended particles was used to quantify such air flows based on hydrodynamic similarity matching. The good agreement between µPIV results and expected acinar flow phenomena suggest that the microfluidic platform may serve in the near future as an attractive in vitro tool to investigate directly airborne representative particle transport and deposition in the acinar regions of the lungs. PMID:27214269

  11. ATP release, generation and hydrolysis in exocrine pancreatic duct cells

    DEFF Research Database (Denmark)

    Kowal, Justyna Magdalena; Yegutkin, G.G.; Novak, Ivana

    2015-01-01

    purine homeostasis in a pancreatic duct cell model involving: ATP release by several mechanisms and subsequent nucleotide breakdown and ATP regeneration via counteracting nucleotide-inactivating and nucleotide-phosphorylating ecto-enzymes. We suggest that extracellular ATP homeostasis in pancreatic ducts......Extracellular adenosine triphosphate (ATP) regulates pancreatic duct function via P2Y and P2X receptors. It is well known that ATP is released from upstream pancreatic acinar cells. The ATP homeostasis in pancreatic ducts, which secrete bicarbonate-rich fluid, has not yet been examined. First, our...... aim was to reveal whether pancreatic duct cells release ATP locally and whether they enzymatically modify extracellular nucleotides/sides. Second, we wished to explore which physiological and pathophysiological factors may be important in these processes. Using a human pancreatic duct cell line, Capan...

  12. Pancreatic regenerating protein (reg Ⅰ) and reg Ⅰ receptor mRNA are upregulated in rat pancreas after induction of acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Martin H Bluth; Sameer A Patel; Brian K Dieckgraefe; Hiroshi Okamoto; Michael E Zenilman

    2006-01-01

    AIM: Pancreatic regenerating protein (reg Ⅰ) stimulates pancreatic regeneration after pancreatectomy and is mitogenic to ductal and β-cells. This suggests that reg Ⅰ and its receptor may play a role in recovery after pancreatic injury. We hypothesized that reg Ⅰ and its receptor are induced in acute pancreatitis.METHODS: Acute pancreatitis was induced in male Wistar rats by retrograde injection of 3% sodium taurocholate into the pancreatic duct. Pancreata and serum were collected 12, 24, and 36 hours after injection and from normal controls (4 rats/group). Reg Ⅰ receptor mRNA, serum reg Ⅰ protein, and tissue reg Ⅰ protein levels were determined by Northern analysis, enzymelinked immunosorbent assay (ELISA), and Western analysis, respectively. Immunohistochemistry was used to localize changes in reg Ⅰ and its receptor.RESULTS: Serum amylase levels and histology confirmed necrotizing pancreatitis in taurocholate treated rats. There was no statistically significant change in serum reg Ⅰ concentrations from controls. However,Western blot demonstrated increased tissue levels of reg Ⅰ at 24 and 36 h. This increase was localized primarily to the acinar cells and the ductal cells by immunohistochemistry. Northern blot demonstrated a significant increase in reg Ⅰ receptor mRNA expression with pancreatitis. Immunohistochemistry localized this increase to the ductal cells, islets, and acinar cells.CONCLUSION: Acute pancreatitis results in increased tissue reg Ⅰ protein levels localized to the acinar and ductal cells, and a parallel threefold induction of reg Ⅰ receptor in the ductal cells, islets, and acinar cells. These changes suggest that induction of reg Ⅰ and its receptor may be important for recovery from acute pancreatitis.

  13. Phospho-Aspirin (MDC-22) Prevents Pancreatic Carcinogenesis in Mice.

    Science.gov (United States)

    Mattheolabakis, George; Papayannis, Ioannis; Yang, Jennifer; Vaeth, Brandon M; Wang, Ruixue; Bandovic, Jela; Ouyang, Nengtai; Rigas, Basil; Mackenzie, Gerardo G

    2016-07-01

    Pancreatic cancer is a deadly disease with a dismal 5-year survival rate of <6%. The currently limited treatment options for pancreatic cancer underscore the need for novel chemopreventive and therapeutic agents. Accumulating evidence indicates that aspirin use is associated with a decreased risk of pancreatic cancer. However, the anticancer properties of aspirin are restricted by its gastrointestinal toxicity and its limited efficacy. Therefore, we developed phospho-aspirin (MDC-22), a novel derivative of aspirin, and evaluated its chemopreventive efficacy in preclinical models of pancreatic cancer. Phospho-aspirin inhibited the growth of human pancreatic cancer cell lines 8- to 12-fold more potently than aspirin; based on the 24-hour IC50 values. In a Panc-1 xenograft model, phospho-aspirin, at a dose of 100 mg/kg/d 5 times per week for 30 days, reduced tumor growth by 78% (P < 0.01 vs. vehicle control). Furthermore, phospho-aspirin prevented pancreatitis-accelerated acinar-to-ductal metaplasia in mice with activated Kras. In p48-Cre;Kras(G12D) mice, cerulein treatment (6 hourly injections two times per week for 3 weeks) led to a significant increase in ductal metaplasia, replacing the majority of the exocrine compartment. Administration of phospho-aspirin 100 mg/kg/day five times per week for 21 days (starting on the first day of cerulein injection) inhibited the acinar-to-ductal metaplasia, reducing it by 87% (P < 0.01, vs. cerulein-treated control). Phospho-aspirin appeared to be safe, with the animals showing no signs of toxicity during treatment. Mechanistically, phospho-aspirin inhibited EGFR activation in pancreatic cancer, an effect consistently observed in pancreatic cancer cells, primary acinar explants and in vivo In conclusion, our findings indicate that phospho-aspirin has strong anticancer efficacy in preclinical models of pancreatic cancer, warranting its further evaluation. Cancer Prev Res; 9(7); 624-34. ©2016 AACR. PMID:27138793

  14. Estrategias para la diferenciación in vitro de células ES de ratón a células acinares pancreáticas

    OpenAIRE

    Rovira Clusellas, Meritxell

    2007-01-01

    Las patologías más importantes del páncreas exocrino, como la pancreatitis crónica (PC) o el cáncer de páncreas, representan un gran problema de salud pública en Europa. En la PC, el tejido acinar es substituido por complejos ductales. Además, es difícil mantener el fenotipo diferenciado de las células acinares en cultivo ya que sufren una transdiferenciación acinar-ductal.Las células madre embrionarias (ES) de ratón han sido utilizadas en la última década para generar in vitro células comple...

  15. Pancreatic Tuberculosis or Autoimmune Pancreatitis

    OpenAIRE

    Ayesha Salahuddin; Muhammad Wasif Saif

    2014-01-01

    Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 relate...

  16. Nitric oxide-induced signalling in rat lacrimal acinar cells

    DEFF Research Database (Denmark)

    Looms, Dagnia Karen; Tritsaris, K.; Dissing, S.

    2002-01-01

    The aim of the present study was to investigate the physiological role of nitric oxide (NO) in mediating secretory processes in rat lacrimal acinar cells. In addition, we wanted to determine whether the acinar cells possess endogenous nitric oxide synthase (NOS) activity by measuring NO productio...... not by itself causing fast transient increases in [Ca2+]i. In addition, we suggest that endogenously produced NO activated by ß-adrenergic receptor stimulation, plays an important role in signalling to the surrounding tissue.......The aim of the present study was to investigate the physiological role of nitric oxide (NO) in mediating secretory processes in rat lacrimal acinar cells. In addition, we wanted to determine whether the acinar cells possess endogenous nitric oxide synthase (NOS) activity by measuring NO production......-adrenergic stimulation and not by a rise in [Ca2+]i alone.   We show that in rat lacrimal acinar cells, NO and cGMP induce Ca2+ release from intracellular stores via G kinase activation. However, the changes in [Ca2+]i are relatively small, suggesting that this pathway plays a modulatory role in Ca2+ signalling, thus...

  17. Expression of dynamin immunoreactivity in experimental pancreatic tumors induced in rat by mancozeb-nitrosomethylurea.

    Science.gov (United States)

    Valentich, M A; Cook, T; Urrutia, R

    1996-04-19

    Dynamins are GTPases which support receptor-mediated endocytosis and bind to several tyrosine kinase receptor-associated proteins known to mediate cell proliferation and differentiation. We have recently established that dynamin expression correlates with normal neuronal (Torre et al., J. Biol. Chem., 269 (1994) 32411-32417) and acinar pancreatic cell differentiation (Cook et al., Mol. Biol. Cell, 6 (1995) 405a). To begin to understand the role of dynamin in neoplastic pancreatic cell differentiation, we have followed the expression of this protein by immunohistochemistry during the development of pancreatic tumors in a mancozeb-nitrosomethylurea (NMU)-based carcinogenesis model recently developed in our laboratory (Monis and Valentich, Carcinogenesis, 14 (1993) 929-933). After a single intraperitoneal injection (50 mg/g body wt) of this carcinogen, rats fed with mancozeb develop pancreatic focal acinar hyperplasia (FACH), dysplastic foci (DYF) displaying acinar-like and ductular-like structures, and ductular-like carcinoma in situ (CIS). After histochemical staining using a monoclonal anti-dynamin antibody, high levels of this protein are consistently observed in well-differentiated acinar tumors (FACH). In contrast, dynamin immunoreactivity is almost undetectable in more advanced lesions showing a ductular-like phenotype (ductular-like DYF and CIS). This change in the expression pattern of dynamin during the progression of acinar into ductular-like DYF and CIS lesions correlates with recent findings from our laboratory showing a differential expression pattern for dynamin in pancreatic cells during embryonic development, with ductular-like precursor cells expressing low levels of this protein. Based upon these results, we conclude that more advanced ductular-like neoplastic cells induced by the carcinogen NMU in rat pancreas behave phenotypically like pancreatic precursor cells in their pattern of expression for dynamin. PMID:8603375

  18. Emodin promoted pancreatic claudin-5 and occludin expression in experimental acute pancreatitis rats

    Institute of Scientific and Technical Information of China (English)

    Xian-Ming Xia; Bang-Ku Li; Shi-Mei Xing; Hai-Ling Ruan

    2012-01-01

    AIM:To investigate the effect of emodin on pancreatic claudin-5 and occludin expression,and pancreatic paracellular permeability in acute pancreatitis (AP).METHODS:Experimental pancreatitis was induced by retrograde injection of 5% sodium taurocholate into the biliopancreatic duct.Emodin was injected via the external jugular vein 0 or 6 h after induction of AP.Rats from sham operation and AP groups were injected with normal saline at the same time.Samples of pancreas were obtained 6 or 12 h after drug administration.Pancreatic morphology was examined with hematoxylin and eosin staining.Pancreatic edema was estimated by measuring tissue water content.Tumor necrosis factor (TNF)-α and interleukin (IL)-6 level were measured by enzyme-linked immunosorbent assay.Pancreatic paracellular permeability was assessed by tissue dye extravasation.Expression of pancreatic claudin-5 and occludin was examined by immunohistology,quantitative real-time reverse transcriptase polymerase chain reaction and western blotting.RESULTS:Pancreatic TNF-α and IL-6 levels,wet/dry ratio,dye extravasation,and histological score were significantly elevated at 3,6 and 12 h following sodium taurocholate infusion; treatment with emodin prevented these changes at all time points.Immunostaining of claudin-5 and occludin was detected in rat pancreas,which was distributed in pancreatic acinar cells,ductal cells and vascular endothelial cells,respectively.Sodium taurocholate infusion significantly decreased pancreatic claudin-5 and occludin mRNA and protein levels at 3,6 and 12 h,and that could be promoted by intravenous administration of emodin at all time points.CONCLUSION:These results demonstrate that emodin could promote pancreatic claudin-5 and occludin expression,and reduce pancreatic paracellular permeability.

  19. Necroptosis: a potential, promising target and switch in acute pancreatitis.

    Science.gov (United States)

    Wang, Gang; Qu, Feng-Zhi; Li, Le; Lv, Jia-Chen; Sun, Bei

    2016-02-01

    Pancreatic acinar cell death is the major pathophysiological change in early acute pancreatitis (AP), and the death modalities are important factors determining its progression and prognosis. During AP, acinar cells undergo two major modes of death, including necrosis and apoptosis. Acinar necrosis can lead to intensely local and systemic inflammatory responses, which both induce and aggravate the lesion. Necrosis has long been considered an unregulated, and passive cell death process. Since the effective interventions of necrosis are difficult to perform, its relevant studies have not received adequate attention. Necroptosis is a newly discovered cell death modality characterized by both necrosis and apoptosis, i.e., it is actively regulated by special genes, while has the typical morphological features of necrosis. Currently, necroptosis is gradually becoming an important topic in the fields of inflammatory diseases. The preliminary results from necroptosis in AP have confirmed the existence of acinar cell necroptosis, which may be a potential target for effectively regulating inflammatory injuries and improving its outcomes; however, the functional changes and mechanisms of necroptosis still require further investigation. This article reviewed the progress of necroptosis in AP to provide a reference for deeply understanding the pathogenic mechanisms of AP and identifying new therapeutic targets. PMID:26514558

  20. Role of cholecystokinin in dietary fat-promoted azaserine-induced pancreatic carcinogenesis in rats.

    OpenAIRE

    Appel, M J; Meijers, M.; Van Garderen-Hoetmer, A.; Lamers, C B; Rovati, L. C.; Sprij-Mooij, D.; Jansen, J B; Woutersen, R.A.

    1992-01-01

    The role of cholecystokinin in dietary fat-promoted pancreatic carcinogenesis was investigated in azaserine-treated rats, using lorglumide, a highly specific cholecystokinin-receptor antagonist. The animals were killed 8 months after the start of treatment. Cholecystokinin, but not dietary unsaturated fat, increased pancreatic weight. Rats treated with cholecystokinin developed more acidophilic atypical acinar cell nodules, adenomas and adenocarcinomas than control animals. Rats maintained on...

  1. Pancreatic Cancer

    Science.gov (United States)

    ... hormones that help control blood sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for developing pancreatic cancer include Smoking Long-term diabetes Chronic pancreatitis Certain ...

  2. Potential role of NADPH oxidase in pathogenesis of pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Wei-Li; Cao; Xiao-Hui; Xiang; Kai; Chen; Wei; Xu; Shi-Hai; Xia

    2014-01-01

    Studies have demonstrated that reactive oxygen species(ROS) are closely related to inflammatory disorders. Nicotinamide adenine dinucleotide phosphate oxidase(NOX), originally found in phagocytes, is the main source of ROS in nonphagocytic cells. Besides directly producing the detrimental highly reactive ROS to act on biomolecules(lipids, proteins, and nucleic acids), NOX can also activate multiple signal transduction pathways, which regulate cell growth, proliferation, differentiation and apoptosis by producing ROS. Recently, research on pancreatic NOX is no longer limited to inflammatory cells, but extends to the aspect of pancreatic acinar cells and pancreatic stellate cells, which are considered to be potentially associated with pancreatitis. In this review, we summarize the literature on NOX protein structure, activation, function and its role in the pathogenesis of pancreatitis.

  3. Acute pancreatitis

    OpenAIRE

    Bo-Guang Fan; Åke Andrén-Sandberg

    2010-01-01

    Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline) addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingest...

  4. Acute pancreatitis

    OpenAIRE

    Bo-Guang Fan; Åke Andrén-Sandberg

    2010-01-01

    Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline) addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion....

  5. ADH-1, Gemcitabine Hydrochloride and Cisplatin in Treating Patients With Metastatic Pancreatic or Biliary Tract Cancer That Cannot Be Removed By Surgery

    Science.gov (United States)

    2013-05-07

    Acinar Cell Adenocarcinoma of the Pancreas; Adenocarcinoma of the Gallbladder; Adult Primary Cholangiocellular Carcinoma; Advanced Adult Primary Liver Cancer; Cholangiocarcinoma of the Gallbladder; Duct Cell Adenocarcinoma of the Pancreas; Localized Unresectable Adult Primary Liver Cancer; Periampullary Adenocarcinoma; Recurrent Adult Primary Liver Cancer; Recurrent Gallbladder Cancer; Recurrent Pancreatic Cancer; Stage II Gallbladder Cancer; Stage III Pancreatic Cancer; Stage IIIA Gallbladder Cancer; Stage IIIB Gallbladder Cancer; Stage IV Pancreatic Cancer; Stage IVA Gallbladder Cancer; Stage IVB Gallbladder Cancer

  6. Effects of Benzodiazepines on Acinar and Myoepithelial Cells

    Science.gov (United States)

    Mattioli, Tatiana M. F.; Alanis, Luciana R. A.; Sapelli, Silvana da Silva; de Lima, Antonio A. S.; de Noronha, Lucia; Rosa, Edvaldo A. R.; Althobaiti, Yusuf S.; Almalki, Atiah H.; Sari, Youssef; Ignacio, Sergio A.; Johann, Aline C. B. R.; Gregio, Ana M. T.

    2016-01-01

    Background: Benzodiazepines (BZDs), the most commonly prescribed psychotropic drugs with anxiolytic action, may cause hyposalivation. It has been previously shown that BZDs can cause hypertrophy and decrease the acini cell number. In this study, we investigated the effects of BZDs and pilocarpine on rat parotid glands, specifically on acinar, ductal, and myoepithelial cells. Methods: Ninety male Wistar rats were divided into nine groups. Control groups received a saline solution for 30 days (C30) and 60 days (C60), and pilocarpine (PILO) for 60 days. Experimental groups received lorazepam (L30) and midazolam (M30) for 30 days. Another group (LS60 or MS60) received lorazepam or midazolam for 30 days, respectively, and saline for additional 30 days. Finally, other groups (LP60 or MP60) received either lorazepam or midazolam for 30 days, respectively, and pilocarpine for additional 30 days. The expression of calponin in myoepithelial cells and the proliferating cell nuclear antigen (PCNA) in acinar and ductal cells were evaluated. Results: Animals treated with lorazepam showed an increase in the number of positive staining cells for calponin as compared to control animals (p acinar and ductal cells and a decrease in the positive staining cells for calponin as compared to midazolam administered with saline (MS60). Conclusion: We found that myoepithelial cells might be more sensitive to the effects of BZD than acinar and ductal cells in rat parotid glands. PMID:27445812

  7. Effects of Benzodiazepines on Acinar and Myoepithelial Cells

    Science.gov (United States)

    Mattioli, Tatiana M. F.; Alanis, Luciana R. A.; Sapelli, Silvana da Silva; de Lima, Antonio A. S.; de Noronha, Lucia; Rosa, Edvaldo A. R.; Althobaiti, Yusuf S.; Almalki, Atiah H.; Sari, Youssef; Ignacio, Sergio A.; Johann, Aline C. B. R.; Gregio, Ana M. T.

    2016-01-01

    Background: Benzodiazepines (BZDs), the most commonly prescribed psychotropic drugs with anxiolytic action, may cause hyposalivation. It has been previously shown that BZDs can cause hypertrophy and decrease the acini cell number. In this study, we investigated the effects of BZDs and pilocarpine on rat parotid glands, specifically on acinar, ductal, and myoepithelial cells. Methods: Ninety male Wistar rats were divided into nine groups. Control groups received a saline solution for 30 days (C30) and 60 days (C60), and pilocarpine (PILO) for 60 days. Experimental groups received lorazepam (L30) and midazolam (M30) for 30 days. Another group (LS60 or MS60) received lorazepam or midazolam for 30 days, respectively, and saline for additional 30 days. Finally, other groups (LP60 or MP60) received either lorazepam or midazolam for 30 days, respectively, and pilocarpine for additional 30 days. The expression of calponin in myoepithelial cells and the proliferating cell nuclear antigen (PCNA) in acinar and ductal cells were evaluated. Results: Animals treated with lorazepam showed an increase in the number of positive staining cells for calponin as compared to control animals (p < 0.05). Midazolam administered with pilocarpine (MP60) induced an increase in the proliferation of acinar and ductal cells and a decrease in the positive staining cells for calponin as compared to midazolam administered with saline (MS60). Conclusion: We found that myoepithelial cells might be more sensitive to the effects of BZD than acinar and ductal cells in rat parotid glands.

  8. Acute Pancreatitis and Pregnancy

    Science.gov (United States)

    ... Acute Pancreatitis > Acute Pancreatitis and Pregnancy test Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is ... of acute pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for ...

  9. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2010-01-01

    Full Text Available Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions : Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  10. Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Bo-Guang Fan

    2010-05-01

    Full Text Available Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions: Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  11. Aberrant innate immune activation following tissue injury impairs pancreatic regeneration.

    Directory of Open Access Journals (Sweden)

    Alexandra E Folias

    Full Text Available Normal tissue architecture is disrupted following injury, as resident tissue cells become damaged and immune cells are recruited to the site of injury. While injury and inflammation are critical to tissue remodeling, the inability to resolve this response can lead to the destructive complications of chronic inflammation. In the pancreas, acinar cells of the exocrine compartment respond to injury by transiently adopting characteristics of progenitor cells present during embryonic development. This process of de-differentiation creates a window where a mature and stable cell gains flexibility and is potentially permissive to changes in cellular fate. How de-differentiation can turn an acinar cell into another cell type (such as a pancreatic β-cell, or a cell with cancerous potential (as in cases of deregulated Kras activity is of interest to both the regenerative medicine and cancer communities. While it is known that inflammation and acinar de-differentiation increase following pancreatic injury, it remains unclear which immune cells are involved in this process. We used a combination of genetically modified mice, immunological blockade and cellular characterization to identify the immune cells that impact pancreatic regeneration in an in vivo model of pancreatitis. We identified the innate inflammatory response of macrophages and neutrophils as regulators of pancreatic regeneration. Under normal conditions, mild innate inflammation prompts a transient de-differentiation of acinar cells that readily dissipates to allow normal regeneration. However, non-resolving inflammation developed when elevated pancreatic levels of neutrophils producing interferon-γ increased iNOS levels and the pro-inflammatory response of macrophages. Pancreatic injury improved following in vivo macrophage depletion, iNOS inhibition as well as suppression of iNOS levels in macrophages via interferon-γ blockade, supporting the impairment in regeneration and the

  12. Obestatin Accelerates the Recovery in the Course of Ischemia/Reperfusion-Induced Acute Pancreatitis in Rats.

    Directory of Open Access Journals (Sweden)

    Jakub Bukowczan

    Full Text Available Several previous studies have shown that obestatin exhibits protective and regenerative effects in some organs including the stomach, kidney, and the brain. In the pancreas, pretreatment with obestatin inhibits the development of cerulein-induced acute pancreatitis, and promotes survival of pancreatic beta cells and human islets. However, no studies investigated the effect of obestatin administration following the onset of experimental acute pancreatitis.The aim of this study was to evaluate the impact of obestatin therapy in the course of ischemia/reperfusion-induced pancreatitis. Moreover, we tested the influence of ischemia/reperfusion-induced acute pancreatitis and administration of obestatin on daily food intake and pancreatic exocrine secretion.Acute pancreatitis was induced by pancreatic ischemia followed by reperfusion of the pancreas. Obestatin (8 nmol/kg/dose was administered intraperitoneally twice a day, starting 24 hours after the beginning of reperfusion. The effect of obestatin in the course of necrotizing pancreatitis was assessed between 2 and 14 days, and included histological, functional, and biochemical analyses. Secretory studies were performed on the third day after sham-operation or induction of acute pancreatitis in conscious rats equipped with chronic pancreatic fistula.Treatment with obestatin ameliorated morphological signs of pancreatic damage including edema, vacuolization of acinar cells, hemorrhages, acinar necrosis, and leukocyte infiltration of the gland, and led to earlier pancreatic regeneration. Structural changes were accompanied by biochemical and functional improvements manifested by accelerated normalization of interleukin-1β level and activity of myeloperoxidase and lipase, attenuation of the decrease in pancreatic DNA synthesis, and by an improvement of pancreatic blood flow. Induction of acute pancreatitis by pancreatic ischemia followed by reperfusion significantly decreased daily food intake and

  13. Adrenoceptor-activated nitric oxide synthesis in salivary acinar cells

    DEFF Research Database (Denmark)

    Looms, Dagnia; Dissing, Steen; Tritsaris, Katerina;

    2000-01-01

    We investigated the cellular regulation of nitric oxide synthase (NOS) activity in isolated acinar cells from rat parotid and human labial salivary glands, using the newly developed fluorescent nitric oxide (NO) indicator, DAF-2. We found that sympathetic stimulation with norepinephrine (NE) caused...... a strong increase in NO synthesis that was not seen after parasympathetic stimulation with acetylcholine. In rat parotid acinar cells, we furthermore investigated to which extent the NOS activity was dependent on the intracellular free Ca2+ concentration ([Ca2+]i) by simultaneously measuring NO synthesis...... not cause significant NO synthesis. We furthermore found that activating adrenoceptors with NE causes synthesis of cGMP by activating a guanylyl cyclase, and that an enhanced [cGMP] evoked by use of caged cGMP causes Ca2+ release from internal stores. Thus, upon sympathetic stimulation, salivary gland acini...

  14. Action of Antiproteases on the Inflammatory Response in Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Chun-Chia Chen

    2007-07-01

    Full Text Available The spectrum of acute pancreatitis ranges from mild edematous disease to a severe necrotizing process which is usually accompanied by local or systemic complications and even mortality. Early deaths (within the first week due to severe acute pancreatitis are generally caused by massive inflammatory responses which result in multiple organ failure. Although the exact mechanisms which trigger the inflammatory and necrotizing processes are not completely understood, it is generally accepted that autodigestion and activated leukocytes play important roles in the pathogenesis of acute pancreatitis. Proinflammatory cytokines are associated with systemic inflammatory response syndrome and multiple organ failure syndrome in acute pancreatitis. A compensatory anti-inflammatory response occurs in parallel with systemic inflammatory response syndrome. Trypsin secreted by the pancreatic acinar cells activates proteaseactivated receptor-2 which can result in the production of cytokines. Protease inhibitors such as aprotinin, gabexate mesilate, nafamostat mesilate, ulinastatin, etc. can inhibit the various enzymes and inflammatory response in experimental and clinical studies. Thus, protease inhibitors have been considered as a potential treatment to inhibit the pancreatic inflammation in acute pancreatitis. The beneficial effects of antiproteases on experimental severe acute pancreatitis may be, in part, due to the modulation of inflammatory cytokine responses. The effect of protease inhibitors on the inflammatory response in human acute pancreatitis deserves further study.

  15. Postmortem acinar autolysis in rat sublingual gland: a morphometric study

    Directory of Open Access Journals (Sweden)

    Leticia Rodrigues Nery

    2010-10-01

    Full Text Available ABSTRACT OBJECTIVE: To analyze and to quantify morphological acinar postmortem changes in rat sublingual glands (SLG. MATERIAL AND METHODSs: Fifty rats were divided into two groups of 25 animals each. Group I was used for morphological and morphometric evaluations and group II for the determination of gland density and processed gland volume. Acinar autolytic changes were studied at 0 (control group, 3, 6, 12 and 24 h postmortem periods. The morphometric analysis of the volume density (Vv and total volume (Vt of intact (ia and autolyzed (aa acini was performed under light microscopy using a Zeiss II integration grid with 100 symmetrically distributed points. RESULTS: Morphologically, temporal progressive nuclear alterations and gradual loss of the structural architecture of acinar cells were found. Regarding quantitative results, both the Vvaa and the Vvia showed statistically significant differences among all postmortem periods (p0.05, respectively. Vtaa increased from 0.18 mm³ at 0 h to 38.17 mm³ at 12 h, while Vtia showed a decrease from 33.47 mm³ to 0 mm³ between 3-24 h postmortem. Data concerning Vtaa were adjusted by two-variable linear regression, obtaining the equation: y=-3.54 + 3.38x (r²=0.90. The Vtaa growth rate calculated by this equation was 3.38 mm³/h between 0-12 h. CONCLUSION: Acinar autolysis on rat SLG demonstrated the most significant signs during the first 6 h postmortem and was widely spread through the gland at 12 h.

  16. Salivary gland homeostasis is maintained through acinar cell self-duplication.

    Science.gov (United States)

    Aure, Marit H; Konieczny, Stephen F; Ovitt, Catherine E

    2015-04-20

    Current dogma suggests that salivary gland homeostasis is stem cell dependent. However, the extent of stem cell contribution to salivary gland maintenance has not been determined. We investigated acinar cell replacement during homeostasis, growth, and regeneration, using an inducible CreER(T2) expressed under the control of the Mist1 gene locus. Genetic labeling, followed by a chase period, showed that acinar cell replacement is not driven by the differentiation of unlabeled stem cells. Analysis using R26(Brainbow2.1) reporter revealed continued proliferation and clonal expansion of terminally differentiated acinar cells in all major salivary glands. Induced injury also demonstrated the regenerative potential of pre-labeled acinar cells. Our results support a revised model for salivary gland homeostasis based predominantly on self-duplication of acinar cells, rather than on differentiation of stem cells. The proliferative capacity of differentiated acinar cells may prove critical in the implementation of cell-based strategies to restore the salivary glands.

  17. [Pancreatic Diseases].

    Science.gov (United States)

    Schöfl, Rainer

    2016-06-22

    The author presents his personal choice of practical relevant papers of pancreatic diseases from 2014 to 2015. Nutritional factors and hypertriglycidemia are discussed as causes of acute pancreatitis. Tools to avoid post-ERCP(endoscopic retrograde cholangiopancreatography) pancreatitis are described and the natural course of fluid collections and pseudocysts is demonstrated. The value of secretin-MRCP(magnetic resonance cholangiopancreatography) for diagnosis of chronic pancreatitis is illustrated. Data help to choose the minimally effective prednisolone dose in autoimmune pancreatitis. The increased prevalence of fractures in patients with chronic pancreatitis highlights the necessity of screening for bone density loss. The association of vitamin D intake with pancreatic cancer is described. The probability of cancer in IPNM is shown and innovative surgical concepts to reduce the loss of pancreatic function are presented. Finally neoadjuvant concepts for the treatment of pancreatic cancer are highlighted. PMID:27329710

  18. Ultrastructural morphometry of parotid acinar cells following fractionated irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Grehn, A.-L.; Gustafsson, H.; Franzen, L.; Thornell, L.-E.; Henriksson, R. [Umeaa Univ. (Sweden)

    1997-01-01

    The aim of this study was to evaluate the long term effects on the ultrastructure of parotid glands after fractionated irradiation. The method implemented involved 5 x 6 Gy and 5 x 8 Gy, Monday to Friday 6 MV photons. By unilateral irradiation, the contralateral parotid gland served as a control. Although irradiation diminished the acinar cell density in light microscopic sections from 75 to 32% after 5 x 8 Gy of irradiation, ultrastructural morphometry could not detect any statistically significant differences in acinar cell size, nuclear size, nuclear density, granule area, mean granule size, or granule density. In general, greater differences were seen between rats receiving 30 or 40 Gy, on both the irradiated and the control side, than between the irradiated side and the control side. This was interpreted as due to differences in the nutritional state of the animals. This analysis concluded that individual acinar cells that survive irradiation seem not to be damaged in the long term when evaluated at the ultrastructural level. The study further stresses the importance of adequate sampling sizes and the use of adequate controls. (author).

  19. N-acetylcysteine in acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Laura; Ramudo; Manuel; A; Manso

    2010-01-01

    Premature trypsinogen activation and production of oxygen free radicals (OFR) are early pathogenic events which occur within acinar cells and trigger acute pancreatitis (AP). OFR exert their harmful effects on various cell components causing lipid peroxidation, disturbances in calcium homeostasis and DNA damage, which lead to increased cell injury and eventually cell death. This review presents the most recent data concerning the effects of N-Acetylcysteine (NAC), in the treatment of AP. NAC is an antioxidant capable of restoring the levels of Glutathione, the most important cellular antioxidant. Studies show the benef icial effects of NAC treatment in preventing OFR production and therefore attenuating oxidative damage. Additionally, NAC treatment has been shown to prevent the increase in cytosolic Ca2+ concentration and reduce the accumulation of enzymes in acinar cells during AP. The prevention, by NAC, of these pathological events occurring within acinar would contribute to reducing the severity of AP. NAC is also capable of reducing the activation of transcription factors especially sensitive to the cellular redox state, such as Nuclear factor-κB, signal transducer and activator of transcription-3 and mitogenactivated protein kinase. This leads to a down-regulation of cytokines, adhesion molecules and chemokine expression in various cell types during AP. These f indingspoint to NAC as a powerful therapeutic treatment, attenuating oxidative-stress-induced cell injury and other pathological events at early stages of AP, and potentially contributing to reducion in the severity of disease.

  20. New Frontiers in the Pharmacological Prevention of Post-ERCP Pancreatitis: The Cytokines

    Directory of Open Access Journals (Sweden)

    Demols A

    2003-01-01

    Full Text Available Acute pancreatitis is a major complication of endoscopic retrograde cholangiopancreatography (ERCP, its incidence varying with the indications for the procedure (less than 5% for the management of common bile duct stones and up to 20% in the case of sphincter of Oddi dysfunction and also with events occurring during the ERCP such as acinarization and pancreatic sphincterotomy. If the triggering event of premature intra-acinar activation of trypsinogen is unknown, the acinar cell injury leads to oxidative stress, nuclear translocation of nuclear factor kappa B and subsequent transcription of chemo- and pro-inflammatory cytokines. These events are followed by chemoattraction and activation of monomacrophages, T lymphocytes and neutrophils which are responsible for acinar necrosis and amplification of the pro-inflammatory cascade. Finally, after amplification by Kupffer cells, systemic inflammatory response syndrome and multiple organ failure occur. All these events take place within a very short period of time, thus offering a very short therapeutic window during which it is theoretically possible to modulate the severity of human pancreatitis. Prophylactic immunomodulation of this pro-inflammatory cascade is attractive, using anti-inflammatory cytokines, specific inhibitors of pro-inflammatory cytokines or inhibitors of the nuclear translocation of the nuclear factor kappa B. Good results have been obtained in experimental models, reducing the acute pancreatitis severity and its systemic complications. The use of immunomodulators in the prevention of human post-ERCP pancreatitis is actually restricted to recombinant interleukin-10. Three of four randomized clinical trials, confirmed by a meta-analysis, have shown that prophylactic injection of recombinant interleukin-10 can significantly reduce the incidence of acute pancreatitis and may decrease the length of the hospital stay. The use of recombinant interleukin-10 in this indication has to be

  1. Co-localization hypothesis: A mechanism for the intrapancreatic activation of digestive enzymes during the early phases of acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Gijs JD van Acker; George Perides; Michael L Steer

    2006-01-01

    Acute pancreatitis is generally believed to be a disease in which the pancreas is injured by digestive enzymes that it normally produces. Most of the potentially harmful digestive enzymes produced by pancreatic acinar cells are synthesized and secreted as inactive zymogens which are normally activated only upon entry into the duodenum but, during the early stages of acute pancreatitis, those zymogens become prematurely activated within the pancreas and, presumably, that activation occurs within pancreatic acinar cells. The mechanisms responsible for intracellular activation of digestive enzyme zymogens have not been elucidated with certainty but, according to one widely recognized theory (the "co-localization hypothesis"), digestive enzyme zymogens are activated by lysosomal hydrolases when the two types of enzymes become co-localized within the same intracellular compartment. This review focuses on the evidence supporting the validity of the co-localization hypothesis as an explanation for digestive enzyme activation during the early stages of pancreatitis.The findings, summarized in this review, support the conclusion that co-localization of lysosomal hydrolases with digestive enzyme zymogens plays a critical role in permitting the intracellular activation of digestive enzymesthat leads to acinar cell injury and pancreatitis.

  2. Cholecystokinin acts as an essential factor in the exacerbation of pancreatic bile duct ligation-induced rat pancreatitis model under non-fasting condition.

    Science.gov (United States)

    Yoshinaga, K; Washizuka, M; Segawa, Y

    2000-09-01

    We examined the influence of 2 gut hormones involved in the enhancement of pancreatic exocrine secretion, secretin and cholecystokinin (CCK), in the exacerbation of pancreatitis. We also examined the role of the vagal system, which was considered to be a transmission route for these hormones. Our model of pancreatitis in the rat was prepared by pancreatic bile duct ligation (PBDL), which simultaneously ligated the pancreatic duct and the common bile duct. Serum amylase activity and histopathological changes in the pancreas were used as indices of pancreatitis. We also measured the volume of pancreatic juice, as well as the amylase activity and protein level of the pancreatic juice, as indices of increased pancreatic exocrine secretion. Two gut hormones were given 6 times at 1-h intervals. Administration of secretin (1-3 microg/kg, s.c.) did not influence serum amylase activity in rats with PBDL-induced pancreatitis. However, food stimulation and administration of CCK-8 (1 microg/kg, s.c.) increased serum amylase activity and promoted vacuolation of the pancreatic acinar cells in rats with PBDL-induced pancreatitis. Administration of atropine (3 mg/kg, s.c.) or a CCK1-receptor antagonist, Z-203 (0.1 mg/kg, i.v.), inhibited food-stimulated or CCK-8-induced (1 microg/kg, s.c.) enhancement of pancreatic exocrine secretion and exacerbation after the development of PBDL-induced pancreatitis. These results suggest that not secretin, which regulates the volume of pancreatic juice, but CCK, which regulates the secretion of pancreatic enzymes via the vagal system, plays an essential role in food-stimulated exacerbation after the development of pancreatitis.

  3. Pancreatic Tuberculosis or Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Ayesha Salahuddin

    2014-01-01

    Full Text Available Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 related systemic diseases and tuberculosis appear to have some similarities. Case Report. We report a case of a 59-year-old Southeast Asian male who presented with fever, weight loss, and obstructive jaundice. CT scan revealed pancreatic mass and enlarged peripancreatic lymph nodes. Endoscopic ultrasound-guided fine needle aspiration confirmed the presence of mycobacterium tuberculosis. Patient also had high immunoglobulin G4 levels suggestive of autoimmune pancreatitis. He was started on antituberculosis medications and steroids. Clinically, he responded to treatment. Follow-up imaging showed findings suggestive of chronic pancreatitis. Discussion. Pancreatic tuberculosis and autoimmune pancreatitis can mimic pancreatic malignancy. Accurate diagnosis is imperative as unnecessary surgical intervention can be avoided. Endoscopic ultrasound-guided fine needle aspiration seems to be the diagnostic test of choice for pancreatic masses. Long-term follow-up is warranted in cases of chronic pancreatitis.

  4. Complicated Pancreatitis

    NARCIS (Netherlands)

    Bakker, O.J.

    2015-01-01

    Research questions addressed in this thesis: What is the accuracy of serum blood urea nitrogen as early predictor of complicated pancreatitis? ; What is difference in clinical outcome between patients with pancreatic parenchymal necrosis and patients with extrapancreatic necrosis without necrosis

  5. Complicated Pancreatitis

    OpenAIRE

    Bakker, O.J.

    2015-01-01

    Research questions addressed in this thesis: What is the accuracy of serum blood urea nitrogen as early predictor of complicated pancreatitis? ; What is difference in clinical outcome between patients with pancreatic parenchymal necrosis and patients with extrapancreatic necrosis without necrosis of the pancreatic parenchyma? ; What is the impact of organ failure on mortality in necrotizing pancreatitis? ; Based on individual patient data from randomized trials, does early enteral tube feedin...

  6. Childhood pancreatitis.

    Science.gov (United States)

    Uretsky, G; Goldschmiedt, M; James, K

    1999-05-01

    Acute pancreatitis is a rare finding in childhood but probably more common than is generally realized. This condition should be considered in the evaluation of children with vomiting and abdominal pain, because it can cause significant morbidity and mortality. Clinical suspicion is required to make the diagnosis, especially when the serum amylase concentration is normal. Recurrent pancreatitis may be familial as a result of inherited biochemical or anatomic abnormalities. Patients with hereditary pancreatitis are at high risk for pancreatic cancer.

  7. p53 mutations cooperate with oncogenic Kras to promote adenocarcinoma from pancreatic ductal cells.

    Science.gov (United States)

    Bailey, J M; Hendley, A M; Lafaro, K J; Pruski, M A; Jones, N C; Alsina, J; Younes, M; Maitra, A; McAllister, F; Iacobuzio-Donahue, C A; Leach, S D

    2016-08-11

    Pancreatic cancer is one of the most lethal malignancies, with virtually all patients eventually succumbing to their disease. Mutations in p53 have been documented in >50% of pancreatic cancers. Owing to the high incidence of p53 mutations in PanIN 3 lesions and pancreatic tumors, we interrogated the comparative ability of adult pancreatic acinar and ductal cells to respond to oncogenic Kras and mutant Tp53(R172H) using Hnf1b:CreER(T2) and Mist1:CreER(T2) mice. These studies involved co-activation of a membrane-tethered GFP lineage label, allowing for direct visualization and isolation of cells undergoing Kras and mutant p53 activation. Kras activation in Mist1(+) adult acinar cells resulted in brisk PanIN formation, whereas no evidence of pancreatic neoplasia was observed for up to 6 months following Kras activation in Hnf1beta(+) adult ductal cells. In contrast to the lack of response to oncogenic Kras alone, simultaneous activation of Kras and mutant p53 in adult ductal epithelium generated invasive PDAC in 75% of mice as early as 2.5 months after tamoxifen administration. These data demonstrate that pancreatic ductal cells, whereas exhibiting relative resistance to oncogenic Kras alone, can serve as an effective cell of origin for pancreatic ductal adenocarcinoma in the setting of gain-of-function mutations in p53. PMID:26592447

  8. Role of bile acids in carcinogenesis of pancreatic cancer: An old topic with new perspective.

    Science.gov (United States)

    Feng, Hui-Yi; Chen, Yang-Chao

    2016-09-01

    The role of bile acids in colorectal cancer has been well documented, but their role in pancreatic cancer remains unclear. In this review, we examined the risk factors of pancreatic cancer. We found that bile acids are associated with most of these factors. Alcohol intake, smoking, and a high-fat diet all lead to high secretion of bile acids, and bile acid metabolic dysfunction is a causal factor of gallstones. An increase in secretion of bile acids, in addition to a long common channel, may result in bile acid reflux into the pancreatic duct and to the epithelial cells or acinar cells, from which pancreatic adenocarcinoma is derived. The final pathophysiological process is pancreatitis, which promotes dedifferentiation of acinar cells into progenitor duct-like cells. Interestingly, bile acids act as regulatory molecules in metabolism, affecting adipose tissue distribution, insulin sensitivity and triglyceride metabolism. As a result, bile acids are associated with three risk factors of pancreatic cancer: obesity, diabetes and hypertriglyceridemia. In the second part of this review, we summarize several studies showing that bile acids act as cancer promoters in gastrointestinal cancer. However, more question are raised than have been solved, and further oncological and physiological experiments are needed to confirm the role of bile acids in pancreatic cancer carcinogenesis. PMID:27672269

  9. Recruitment and activation of pancreatic stellate cells from the bone marrow in pancreatic cancer: a model of tumor-host interaction.

    Directory of Open Access Journals (Sweden)

    Christopher J Scarlett

    Full Text Available BACKGROUND AND AIMS: Chronic pancreatitis and pancreatic cancer are characterised by extensive stellate cell mediated fibrosis, and current therapeutic development includes targeting pancreatic cancer stroma and tumor-host interactions. Recent evidence has suggested that circulating bone marrow derived stem cells (BMDC contribute to solid organs. We aimed to define the role of circulating haematopoietic cells in the normal and diseased pancreas. METHODS: Whole bone marrow was harvested from male β-actin-EGFP donor mice and transplanted into irradiated female recipient C57/BL6 mice. Chronic pancreatitis was induced with repeat injections of caerulein, while carcinogenesis was induced with an intrapancreatic injection of dimethylbenzanthracene (DMBA. Phenotype of engrafted donor-derived cells within the pancreas was assessed by immunohistochemistry, immunofluorescence and in situ hybridisation. RESULTS: GFP positive cells were visible in the exocrine pancreatic epithelia from 3 months post transplantation. These exhibited acinar morphology and were positive for amylase and peanut agglutinin. Mice administered caerulein developed chronic pancreatitis while DMBA mice exhibited precursor lesions and pancreatic cancer. No acinar cells were identified to be donor-derived upon cessation of cerulein treatment, however rare occurrences of bone marrow-derived acinar cells were observed during pancreatic regeneration. Increased recruitment of BMDC was observed within the desmoplastic stroma, contributing to the activated pancreatic stellate cell (PaSC population in both diseases. Expression of stellate cell markers CELSR3, PBX1 and GFAP was observed in BMD cancer-associated PaSCs, however cancer-associated, but not pancreatitis-associated BMD PaSCs, expressed the cancer PaSC specific marker CELSR3. CONCLUSIONS: This study demonstrates that BMDC can incorporate into the pancreas and adopt the differentiated state of the exocrine compartment. BMDC that

  10. Hereditary pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Richard M Charnley

    2003-01-01

    Hereditary pancreatitis is an autosomal dominant condition,which results in recurrent attacks of acute pancreatitis,progressing to chronic pancreatitis often at a young age.The majority of patients with hereditary pancreatitis expressone of two mutations (R122H or N29I) in the cationictrypsinogen gene (PRSS1 gene). It has been hypothesisedthat one of these mutations, the R122H mutation causespancreatitis by altering a trypsin recognition site sopreventing deactivation of trypsin within the pancreas andprolonging its action, resulting in autodigestion. Families withthese two mutations have been identified in many countriesand there are also other rarer mutations, which have alsobeen linked to hereditary pancreatitis.Patients with hereditary pancreatitis present in the sameway as those with sporadic pancreatitis but at an earlierage. It is common for patients to remain undiagnosed formany years, particularly ifthey present with non-specificsymptoms. Hereditary pancreatitis should always beconsidered in patients who present with recurrent pancreatitiswith a family history of pancreatic disease. If patients withthe 2 common mutations are compared, those with theR122H mutation are more likely to present at a younger ageand are more likely to require surgical intervention than thosewith N29I. Hereditary pancreatitis carries a 40 % lifetimerisk of pancreatic cancer with those patients aged between50 to 70 being most at risk in whom screening tests maybecome important.

  11. Pentoxifylline Treatment in Acute Pancreatitis (AP)

    Science.gov (United States)

    2016-09-14

    Acute Pancreatitis (AP); Gallstone Pancreatitis; Alcoholic Pancreatitis; Post-ERCP/Post-procedural Pancreatitis; Trauma Acute Pancreatitis; Hypertriglyceridemia Acute Pancreatitis; Idiopathic (Unknown) Acute Pancreatitis; Medication Induced Acute Pancreatitis; Cancer Acute Pancreatitis; Miscellaneous (i.e. Acute on Chronic Pancreatitis)

  12. Autoimmune pancreatitis

    DEFF Research Database (Denmark)

    Detlefsen, Sönke; Drewes, Asbjørn M

    2009-01-01

    bile duct. Obstructive jaundice is a common symptom at presentation, and pancreatic cancer represents an important clinical differential diagnosis. In late stages of the disease, the normal pancreatic parenchyma is often replaced by large amounts of fibrosis. Histologically, there seem to be two...... AIP responds to steroid treatment, also a trial with steroids, can help to differentiate AIP from pancreatic cancer. OUTLOOK AND DISCUSSION: This review presents the pathological, radiologic and laboratory findings of AIP. Moreover, the treatment and pathogenesis are discussed.......BACKGROUND: Autoimmune pancreatitis (AIP) is a relatively newly recognized type of pancreatitis that is characterized by diffuse or focal swelling of the pancreas due to lymphoplasmacytic infiltration and fibrosis of the pancreatic parenchyma. MATERIAL AND METHODS: A PubMed literature search was...

  13. Dexamethasone mediates protection against acute pancreatitis via upregulation of pancreatitis-associated proteins

    Institute of Scientific and Technical Information of China (English)

    Emad Kandil; Yin-Yao Lin; Martin H Bluth; Hong Zhang; Gabriel Levi; Michael E Zenilman

    2006-01-01

    AIM:To examine the influence of dexamethasone on pancreatitis-associated protein (PAP) gene expression using both in vitro and in vivo models of acute pancreatitis and to study how PAP gene expression correlates with severity of pancreatitis.METHODS:In vifro, IL-6 stimulated pancreas acinar AR42J cells were cultured with increasing concentrations of dexamethasone and assayed for PAP expression (RT-PCR). In vivo, pancreatitis was induced in rats by retrograde injection of 40 g/L taurocholate into the pancreatic duct. Animals were pretreated with dexamethasone (2 mg/kg) daily or saline for 4 d.Pancreata and serum were harvested after 24 h and gene expression levels of PAP Ⅰ , Ⅱ and Ⅲ were measured by RT-PCR. Severity of pancreatitis was based on serum amylase, pancreatic wet weight, and histopathological score.RESULTS:In vitro, dexamethasone and IL-6 induced a marked transcription of PAP Ⅰ, Ⅱ and Ⅲ genes in AR42J cells at 24 h (P < 0.05 for all comparisons). In vivo,pancreas mRNA levels of PAP Ⅰ, Ⅱ or Ⅲ increased by 2.6-fold, 1.9-fold, and 1.3-fold respectively after dexamethasone treatment, compared with saline treated animals. Serum amylase levels and edema were significantly lower in the dexamethasone group compared with the saline group. Histopathologic evaluation revealed less inflammation and necrosis in pancreata obtained from dexamethasone treated animals (P < 0.05).CONCLUSION:Dexamethasone significantly decreases the severity of pancreatitis. The protective mechanism of dexamethasone may be via upregulating PAP gene expression during injury.

  14. Chronic pancreatitis and pancreatic carcinoma.

    OpenAIRE

    Evans, J D; Morton, D. G.; Neoptolemos, J. P.

    1997-01-01

    The differential diagnosis between pancreatic cancer and chronic pancreatitis is very important as the management and prognosis of these two diseases is different. In most patients with pancreatic disease, the diagnosis can be established but there is a subgroup of patients in whom it is difficult to differentiate between these conditions because the clinical presentation is often similar and currently available diagnostic tests may be unable to distinguish between an inflammatory or neoplast...

  15. Effect of parenteral and early intrajejunal nutrition on pancreatic digestive enzyme synthesis,storage and discharge in dog models of acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Huan-Long Qin; Zhen-Dong Su; Lei-Guang Hu; Zai-Xian Ding; Qing-Tian Lin

    2007-01-01

    AIM:To study the effect of early intrajejunal nutrition on enzyme-protein synthesis and secretion during acute pancreatitis.METHODS:Fifteen dogs were randomly divided into parenteral nutrition(n = 7)and early intrajejunal nutrition groups(n = 8).An acute pancreatitis model was induced by injecting 5% sodium taurocholate and trypsin into the pancreas via the pancreatic duct.Intrajejunal nutrition was delivered with a catheter via a jejunostomy tube after the model was established for 24 h.On d 1 and 7 and at the beginning of nutritional support,radioactive tracing and electron microscopes were used to evaluate the enzyme-protein synthesis in acinar cells,the subcellular fractionation and the change in zymogen granules after 1.85×106 Bq L-3H phenylalanine was infused at 30,60,120,and 180 min.RESULTS:The 3H radioactivity in pancreatic acinar cells reached its peak level at 60 min,and the contents in the early intrajejunal nutrition group were higher than those in the parenteral nutrition group,which were then decreased.The mean number and area of zymogen granules did not show any significant statistical difference in both groups on d 1 or on d 7(P > 0.05).CONCLUSION:Early intrajejunal nutrition might be effective in dogs with acute pancreatitis.

  16. Mechanisms of dexamethasone-mediated chemokine down-regulation in mild and severe acute pancreatitis

    OpenAIRE

    Yubero, S.; Ramudo, L.; Manso, M.A.; De Dios, I.

    2009-01-01

    Abstract This study aimed to investigate the role of therapeutic dexamethaxone (Dex) treatment on the mechanisms underlying chemokine expression during mild and severe acute pancreatitis (AP) experimentally induced in rats. Regardless of the AP severity, Dex (1 mg/kg), administered 1 hour after AP, reduced the acinar cell activation of extracellular signal-regulated kinase (ERK) and c-Jun-NH2-terminal kinase (JNK) but failed to reduce p38-mitogen activated protein kinas (MAPK) in s...

  17. Bicaudal C1 promotes pancreatic NEUROG3+ endocrine progenitor differentiation and ductal morphogenesis

    DEFF Research Database (Denmark)

    Lemaire, Laurence A; Goulley, Joan; Kim, Yung Hae;

    2015-01-01

    that line the ducts during development, and in the ducts after birth, but not in differentiated endocrine or acinar cells. Genetic inactivation of Bicc1 leads to ductal cell over-proliferation and cyst formation. Transcriptome comparison between WT and Bicc1 KO pancreata, before the phenotype onset, reveals......, and suggest a new candidate gene for syndromes associating kidney dysplasia with pancreatic disorders, including diabetes....

  18. Essential role of monocytes and macrophages in the progression of acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Pratima; Shrivastava; Madhav; Bhatia

    2010-01-01

    Acute pancreatitis(AP) is an inflammatory condition of the pancreas caused by an imbalance in factors involved in maintaining cellular homeostasis.Earliest events in AP occur within acinar cells accompanied by other principal contributors to the inflammatory response i.e.the endothelial cells,immunocytes(granulocytes,monocytes/macrophages,lymphocytes) and neutrophils.Monocytes/macrophages are important inflammatory mediators,involved in the pathophysiology of AP,known to reside in the peritoneal cavity(in t...

  19. [Hereditary pancreatitis].

    Science.gov (United States)

    Dyrla, Przemysław; Nowak, Tomasz; Gil, Jerzy; Adamiec, Cezary; Bobula, Mariusz; Saracyn, Marek

    2016-02-01

    Hereditary pancreatitis (HP) is a rare, heterogeneous familial disease and should be suspected in any patient who has suffered at least two attacks of acute pancreatitis for which there is no underlying cause and unexplained chronic pancreatitis with a family history in a first- or second degree relative. with an early onset, mostly during childhood. Genetic factors have been implied in cases of familial chronic pancreatitis. The most common are mutations of the PRSS1 gene on the long arm of the chromosome 7, encoding for the cationic trypsinogen. The inheritance pattern is autosomal dominant with an incomplete penetrance (80%). The inflammation results in repeated DNA damage, error-prone repair mechanisms and the progressive accumulation of genetic mutations. Risk of pancreatic adenocarcinoma is a major concern of many patients with hereditary chronic pancreatitis, but the individual risk is poorly defined. Better risk models of pancreatic cancer in individual patients based on etiology of pancreatitis, family history, genetics, smoking, alcohol, diabetes and the patient's age are needed. PMID:27000817

  20. Pancreatic cancer

    OpenAIRE

    Kocher, Hemant M.; Alrawashdeh, Wasfi

    2010-01-01

    Pancreatic cancer is the fourth most common cause of cancer death in higher-income countries, with 5-year survival only 10% (range 7%–25%), even in people presenting with early-stage cancer. Risk factors include age, smoking, chronic pancreatitis, a family history, and dietary factors. Diabetes mellitus may also increase the risk.

  1. Regeneration of parotid acinar cells after high radiation doses. A morphological study in rat

    Energy Technology Data Exchange (ETDEWEB)

    Gustafsson, H. [Depts. of Oto-Rhino-Laryngology, Histology and Cell Biology, Umeaa Univ. (Sweden); Franzen, L. [Dept. of Oncology, Umeaa Univ. (Sweden); Henriksson, R. [Dept. of Oncology, Umeaa Univ. (Sweden)

    1995-12-31

    The acute and late effects of fractionated irradiation on rat parotid gland acinar cells were studied by light and electron microscopy. At 10 days after the last irradiation session (6 Gy or 9 Gy daily during five consecutive days) no effects were seen. At 180 days, minor loss of acini was detectable after a total dose of 30 Gy. After 45 Gy a massive acinar loss was seen at that time; the number of acini had diminished and minor duct-like structures and scattered amounts of fibrous stroma dominated the slides. The remaining acini were disorganized and usually larger compared with the control side and to non-irradiated animals. The acinar cells appeared larger than in the controls. The custs were better preserved but the intercalated ducts often seemed to be larger than normal. We suggest that this phenomenon indicates a remaining capacity of the parotid gland to regenerate acinar cells even after high radiation doses. (orig.).

  2. Role of YAP and TAZ in pancreatic ductal adenocarcinoma and in stellate cells associated with cancer and chronic pancreatitis.

    Science.gov (United States)

    Morvaridi, Susan; Dhall, Deepti; Greene, Mark I; Pandol, Stephen J; Wang, Qiang

    2015-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by a fibrotic and inflammatory microenvironment that is formed primarily by activated, myofibroblast-like, stellate cells. Although the stellate cells are thought to contribute to tumorigenesis, metastasis and drug resistance of PDAC, the signaling events involved in activation of the stellate cells are not well defined. Functioning as transcription co-factors, Yes-associated protein (YAP) and its homolog transcriptional co-activator with PDZ-binding motif (TAZ) modulate the expression of genes involved in various aspects of cellular functions, such as proliferation and mobility. Using human tissues we show that YAP and TAZ expression is restricted to the centroacinar and ductal cells of normal pancreas, but is elevated in cancer cells. In particular, YAP and TAZ are expressed at high levels in the activated stellate cells of both chronic pancreatitis and PDAC patients as well as in the islets of Langerhans in chronic pancreatitis tissues. Of note, YAP is up regulated in both acinar and ductal cells following induction of acute and chronic pancreatitis in mice. These findings indicate that YAP and TAZ may play a critical role in modulating pancreatic tissue regeneration, neoplastic transformation, and stellate cell functions in both PDAC and pancreatitis. PMID:26567630

  3. Unsteady diffusional screening in 3D pulmonary acinar structures: from infancy to adulthood.

    Science.gov (United States)

    Hofemeier, Philipp; Shachar-Berman, Lihi; Tenenbaum-Katan, Janna; Filoche, Marcel; Sznitman, Josué

    2016-07-26

    Diffusional screening in the lungs is a physical phenomenon where the specific topological arrangement of alveolated airways of the respiratory region leads to a depletion, or 'screening', of oxygen molecules with increasing acinar generation. Here, we revisit diffusional screening phenomena in anatomically-inspired pulmonary acinar models under realistic breathing maneuvers. By modelling 3D bifurcating alveolated airways capturing both convection and diffusion, unsteady oxygen transport is investigated under cyclic breathing motion. To evaluate screening characteristics in the developing lungs during growth, four representative stages of lung development were chosen (i.e. 3 months, 1 year and 9 months, 3 years and adulthood) that capture distinct morphological acinar changes spanning alveolarization phases to isotropic alveolar growth. Numerical simulations unveil the dramatic changes in O2 transport occurring during lung development, where young infants exhibit highest acinar efficiencies that rapidly converge with age to predictions at adulthood. With increased ventilatory effort, transient dynamics of oxygen transport is fundamentally altered compared to tidal breathing and emphasizes the augmented role of convection. Resolving the complex convective acinar flow patterns in 3D acinar trees allows for the first time a spatially-localized and time-resolved characterization of oxygen transport in the pulmonary acinus, from infancy to adulthood.

  4. Formation of the tetraploid intermediate is associated with the development of cells with more than four centrioles in the elastase-simian virus 40 tumor antigen transgenic mouse model of pancreatic cancer.

    OpenAIRE

    1991-01-01

    The development of pancreatic cancer in transgenic mice expressing the simian virus 40 tumor antigen placed under controlling regions of the elastase I gene is characterized by the sequential appearance of tetraploid and then multiple aneuploid cell populations. Pancreatic tissues from such transgenic mice were studied between 8 and 32 days of age. Virtually 100% of acinar cell nuclei had immunohistochemically detectable tumor antigen by 18 days. Tetraploid cells were demonstrated by DNA cont...

  5. A Suspicious Pancreatic Mass in Chronic Pancreatitis: Pancreatic Actinomycosis

    Directory of Open Access Journals (Sweden)

    F. de Clerck

    2015-01-01

    Full Text Available Introduction. Pancreatic actinomycosis is a chronic infection of the pancreas caused by the suppurative Gram-positive bacterium Actinomyces. It has mostly been described in patients following repeated main pancreatic duct stenting in the context of chronic pancreatitis or following pancreatic surgery. This type of pancreatitis is often erroneously interpreted as pancreatic malignancy due to the specific invasive characteristics of Actinomyces. Case. A 64-year-old male with a history of chronic pancreatitis and repeated main pancreatic duct stenting presented with weight loss, fever, night sweats, and abdominal pain. CT imaging revealed a mass in the pancreatic tail, invading the surrounding tissue and resulting in splenic vein thrombosis. Resectable pancreatic cancer was suspected, and pancreatic tail resection was performed. Postoperative findings revealed pancreatic actinomycosis instead of neoplasia. Conclusion. Pancreatic actinomycosis is a rare type of infectious pancreatitis that should be included in the differential diagnosis when a pancreatic mass is discovered in a patient with chronic pancreatitis and prior main pancreatic duct stenting. Our case emphasizes the importance of pursuing a histomorphological confirmation.

  6. CT and MR imaging of multilocular acinar cell cystadenoma: comparison with branch duct intraductal papillary mucinous neoplasia (IPMNs)

    Energy Technology Data Exchange (ETDEWEB)

    Delavaud, Christophe; Assignies, Gaspard d' ; Vilgrain, Valerie; Vullierme, Marie-Pierre [Hopital Beaujon, Service de Radiologie, Clichy (France); Cros, Jerome [Hopital Beaujon, Service d' Anatomopathologie, Clichy (France); Ruszniewski, Philippe; Hammel, Pascal; Levy, Philippe [Hopital Beaujon, Service de Pancreato-Gastro-Enterologie, Clichy (France); Couvelard, Anne [Hopital Bichat, Service d' Anatomopathologie, Paris (France); Sauvanet, Alain; Dokmak, Safi [Hopital Beaujon, Service de Chirurgie Hepato-Pancreato-Biliaire, Clichy (France)

    2014-09-15

    To describe CT and MR imaging findings of acinar cell cystadenoma (ACC) of the pancreas and to compare them with those of branch duct intraductal papillary mucinous neoplasia (BD-IPMN) to identify distinctive elements. Five patients with ACC and the 20 consecutive patients with histologically proven BD-IPMN were retrospectively included. Clinical and biological information was collected and histological data reviewed. CT and MR findings were analysed blinded to pathological diagnosis in order to identify imaging diagnostic criteria of ACC. Patients with ACC were symptomatic in all but one case and were younger than those with BD-IPMN (p = 0.006). Four radiological criteria allowed for differentiating ACC from IPMN: five or more cysts, clustered peripheral small cysts, presence of cyst calcifications and absence of communication with the main pancreatic duct (p < 0.05). Presence of at least two or three of these imaging criteria had a strong diagnostic value for ACC with a sensitivity of 100 % and 80 % and a specificity of 85 % and 100 %, respectively. Preoperative differential diagnosis between ACC and BD-IPMN can be achieved using a combination of four CT and/or MR imaging criteria. Recognition of ACC patients could change patient management and lead to more conservative treatment. (orig.)

  7. Imaging of pancreatic diseases

    Energy Technology Data Exchange (ETDEWEB)

    Mihashi, H.; Hirose, J.; Hayasaka, K.; Kamikita, Y.; Asano, A. (Asahikawa Medical College, Hokkaido (Japan))

    1981-11-01

    Diagnosing pancreatic diseases using non invasive methods such as ultrasound and computed tomography was reviewed. Images characteristic to pancreatitis and pancreatic cancer were explained. Pancreatic cancer accompanied with pancreatitis was demonstrated on echograms and scintigrams. The necessity of follow-up observation of pancreatitis was stressed.

  8. Acute pancreatitis

    Science.gov (United States)

    ... rate Lab tests that show the release of pancreatic enzymes will be done. These include: Increased blood amylase level Increased serum blood lipase level Increased urine amylase ... swelling of the pancreas include: CT scan of the abdomen MRI of ...

  9. Pancreatitis - children

    Science.gov (United States)

    ... perform lab tests to check the release of pancreatic enzymes. These include tests to check the: Blood amylase level Blood lipase level Urine amylase level Other blood tests ... the pancreas include: Ultrasound of the abdomen (most common) CT ...

  10. Chronic pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Maisonneuve, Patrick; Lowenfels, Albert B

    2002-01-01

    Pancreatic cancer is the fourth leading cause of cancer deaths in the USA in both sexes. Early diagnosis is difficult and the overall mortality rate is high. Individuals at high risk for pancreatic cancer include smokers, and persons with all forms of chronic alcoholic, metabolic, tropical or hereditary pancreatitis. The duration of exposure to inflammation seems to be the major factor involved in the transition from benign to malignant condition. Smoking, which appears to further accelerate the carcinogenic transformation, remains the strongest risk factor amenable to preventive intervention.

  11. Pancreatic Ductal Adenocarcinoma Associated with Autoimmune Pancreatitis

    OpenAIRE

    Pezzilli, Raffaele; Vecchiarelli, Silvia; Di Marco, Maria Cristina; SERRA, CARLA; Santini, Donatella; Calculli, Lucia; Fabbri, Dario; Rojas Mena, Betzabè; Imbrogno, Andrea

    2011-01-01

    Autoimmune pancreatitis (AIP), in contrast to other benign chronic pancreatic diseases, can be cured with immunosuppressant drugs, thus the differentiation of AIP from pancreatic cancer is of particular interest in clinical practice. There is the possibility that some patients with AIP may develop pancreatic cancer, and this possibility contributes to increasing our difficulties in differentiating AIP from pancreatic cancer. We herein report the case of a 70-year-old man in whom pancreatic ad...

  12. Effect of tiron on remote organ injury in rats with severe acute pancreatitis induced by L-arginine.

    Science.gov (United States)

    Ateyya, Hayam; Wagih, Heba M; El-Sherbeeny, Nagla A

    2016-08-01

    Acute pancreatitis (AP) is an acute inflammatory disorder of the pancreas that can be complicated by involvement of other remote organs. Oxidative stress is known to have a crucial role in the development of pancreatic acinar damage and one of the main causes in multisystem organ failure in experimental AP. The aim of the study was to determine the effect of tiron on pancreas and remote organ damage in L-arginine (L-Arg) induced AP rat model. Thirty-two male rats were divided in random into four groups: control, tiron, L-Arg, and tiron with L-Arg. At the end of the experiment, blood samples were withdrawn for biochemical analysis. The pancreas, lung, kidney, and liver were collected for histopathological examination. Estimation of pancreatic water content was done. Analysis of pulmonary, hepatic, renal, and pancreatic lipid peroxide levels (MDA), superoxide dismutase (SOD), and reduced glutathione (GSH) were carried out. Finally, nuclear factor kappa B (NF-κB) and transforming growth factor β1 (TGF-β1) expression in pancreatic tissue was determined. Results indicated that treatment with tiron significantly decreased lipid peroxide levels and markedly increased both SOD activity and GSH level. Moreover, histopathological analysis further confirmed that administration of tiron relatively ameliorates pancreatic acinar cells and remote organ damage. Increased immunoreactivity of NF-κB and TGF-β1 were reduced also by tiron treatment. These findings pointed out the protective role of the mitochondrial antioxidant, tiron against AP induced by L-Arg. PMID:27118662

  13. TNF-alpha-dependent regulation of acute pancreatitis severity by Ly-6C(hi) monocytes in mice.

    Science.gov (United States)

    Perides, George; Weiss, Eric R; Michael, Emily S; Laukkarinen, Johanna M; Duffield, Jeremy S; Steer, Michael L

    2011-04-15

    The roles of monocytes/macrophages and their mechanisms of action in the regulation of pancreatitis are poorly understood. To address these issues, we have employed genetically altered mouse strains that either express the human diphtheria toxin receptor (DTR) coupled to the CD11b promoter or have global deletion of TNF-α. Targeted, conditional depletion of monocytes/macrophages was achieved by administration of diphtheria toxin (DT) to CD11b-DTR mice. We show that in the absence of DT administration, pancreatitis is associated with an increase in pancreatic content of Ly-6C(hi) monocytes/macrophages but that this response is prevented by prior administration of DT to CD11b-DTR mice. DT administration also reduces pancreatic edema and acinar cell injury/necrosis in two dissimilar experimental models of acute pancreatitis (a secretagogue-induced model and a model elicited by retrograde pancreatic duct infusion of sodium taurocholate). In the secretagogue-elicited model, the DT-induced decrease in pancreatitis severity is reversed by adoptive transfer of purified Ly-6C(hi) monocytes harvested from non-DT-treated CD11b-DTR mice or by the transfer of purified Ly-6C(hi) monocytes harvested from TNF-α(+/+) donor mice, but it is not reversed by the transfer of Ly-6C(hi) monocytes harvested from TNF-α(-/-) donors. Our studies indicate that the Ly-6C(hi) monocyte subset regulates the severity of pancreatitis by promoting pancreatic edema and acinar cell injury/necrosis and that this phenomenon is dependent upon the expression of TNF-α by those cells. They suggest that therapies targeting Ly-6C(hi) monocytes and/or TNF-α expression by Ly-6C(hi) monocytes might prove beneficial in the prevention or treatment of acute pancreatitis.

  14. Organ culture studies for pancreatic islet transplantation

    International Nuclear Information System (INIS)

    Data support the usefulness of tissue culture in isolation and preservation of islets prior to transplantation. Rodent islet viability in culture was demonstrated histologically and by functional analyses of hormone production. For reasons that remain to be defined, acinar cells disappeared rapidly in tissue culture, yielding an implant preparation relatively rich in islets and devoid of pancreatic exocrine elements. Isografts of cultured and noncultured islets were well tolerated intraperitoneally and intramuscularly; and prompt and lasting reversal of short- and long-standing experimental diabetes was observed regularly. In vitro studies of rodent islet viability after immunosuppressive treatment of donors or islet cultures showed insulin production comparable to that of control experiments, suggesting that immunologic modification of donors or islets might be feasible in eventual human islet allotransplantation

  15. Pancreatic Cancer Early Detection Program

    Science.gov (United States)

    2014-07-30

    Pancreatic Cancer; Pancreas Cancer; Pancreatic Adenocarcinoma; Familial Pancreatic Cancer; BRCA 1/2; HNPCC; Lynch Syndrome; Hereditary Pancreatitis; FAMMM; Familial Atypical Multiple Mole Melanoma; Peutz Jeghers Syndrome

  16. Elevation of serum pancreatic amylase and distortion of pancreatic cyto-architecture in type 1 diabetes mellitus rats treated with Ocimum gratissimum

    Directory of Open Access Journals (Sweden)

    Okon Uduak Akpan

    2014-01-01

    Full Text Available Background: Diabetes mellitus has been shown to cause severe impairment in exocrine pancreatic function and cyto-architecture. Ocimum grattissimum has been reported to lower blood glucose levels in experimental diabetic animals. This study, therefore, aims to investigate if treatment with O. grattissimum can alleviate these pancreatic complications of diabetes mellitus. The phytoconstituents and median lethal dose of the plant extract were determined. Materials and Methods: Eighteen rats were divided into three groups of six rats each. Diabetes mellitus was induced by single intraperitoneal injection of 65 mg/kg streptozotocin. Group 1 was the control and were given normal feed only; Group 2 was of diabetic untreated rats, while Group 3 was O. grattissimum-treated diabetic rats at a dose of 1,500 mg/kg. After 28 days, blood was collected by cardiac puncture of the anaesthetised animals and the serum was obtained for analysis of serum pancreatic amylase. Permanent preparations using routine biopsy method were employed for histological preparations. Results: Results showed that the level of pancreatic serum amylase in the test groups (diabetic and diabetic-treated were significantly higher (P < 0.05 than the control group, while the diabetic-treated group was significantly lower than the diabetic group. Atrophic acinar tissue without β-cells was noted in the diabetic and diabetic-treated groups. Patchy areas of necrosis, oedematous interstitium, haemorrhagic and necrotic acinar cells were present in diabetic-treated groups. Conclusion: Direct association exists between the hyperglycaemic state caused by diabetes mellitus and the elevation of the serum pancreatic amylase and distortion of pancreatic cyto-achitecture. O. grattissimum-treatment reduced serum pancreatic amylase level to near normal and limit the extent of structural damage.

  17. Pancreatic Protein Tyrosine Phosphatase 1B Deficiency Exacerbates Acute Pancreatitis in Mice.

    Science.gov (United States)

    Bettaieb, Ahmed; Koike, Shinichiro; Chahed, Samah; Bachaalany, Santana; Griffey, Stephen; Sastre, Juan; Haj, Fawaz G

    2016-08-01

    Acute pancreatitis (AP) is a common and devastating gastrointestinal disorder that causes significant morbidity. The disease starts as local inflammation in the pancreas that may progress to systemic inflammation and complications. Protein tyrosine phosphatase 1B (PTP1B) is implicated in inflammatory signaling, but its significance in AP remains unclear. To investigate whether PTP1B may have a role in AP, we used pancreas PTP1B knockout (panc-PTP1B KO) mice and determined the effects of pancreatic PTP1B deficiency on cerulein- and arginine-induced acute pancreatitis. We report that PTP1B protein expression was increased in the early phase of AP in mice and rats. In addition, histological analyses of pancreas samples revealed enhanced features of AP in cerulein-treated panc-PTP1B KO mice compared with controls. Moreover, cerulein- and arginine-induced serum amylase and lipase were significantly higher in panc-PTP1B KO mice compared with controls. Similarly, pancreatic mRNA and serum concentrations of the inflammatory cytokines IL-1B, IL-6, and tumor necrosis factor-α were increased in panc-PTP1B KO mice compared with controls. Furthermore, panc-PTP1B KO mice exhibited enhanced cerulein- and arginine-induced NF-κB inflammatory response accompanied with increased mitogen-activated protein kinases activation and elevated endoplasmic reticulum stress. Notably, these effects were recapitulated in acinar cells treated with a pharmacological inhibitor of PTP1B. These findings reveal a novel role for pancreatic PTP1B in cerulein- and arginine-induced acute pancreatitis. PMID:27461362

  18. Effect of IL-4 on altered expression of complement activation regulators in rat pancreatic cells during severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Cheng Zhang; Chun-Lin Ge; Ren-Xuan Guo; San-Guang He

    2005-01-01

    AIM: To investigate the effect of IL-4 on the altered expression of complement activation regulators in pancreas and pancreatic necrosis during experimental severe acute pancreatitis (SAP).METHODS: SAP model of rats was established by retrograde injection of 5% sodium taurocholate (1 mL/kg)into the pancreatic duct. We immunohistochemically assayed the expression of three complement activation regulators: decay accelerating factor (DAF; CD55), 20ku homologous restriction factor (HRF20; CD59) and membrane cofactor protein (MCP; CD46), in the pancreatic acinar cells of rats at 0, 3, 6, 12, and 24 h after the induction of SAP model. Meanwhile the levels of amylase and lipase were determined, and morphological examination was performed. Then, 61 rats were randomly divided into three groups. Group A (n = 21) received notreatment after the SAP model was established; group B (n = 20) was given IL-4 (8 μg/animal) intraperitoneally 0.5 h before the SAP model was established; group C (n = 20) was given IL-4 (8 μg/animal) intraperitoneally 0.5 h after the SAP model was established. Plasma amylase and lipase, extent of pancreatic necrosis and expression of complement activation regulators were investigated 6 h after the induction of SAP model.RESULTS: Three complement activation regulators were all expressed in pancreatic acinar cells. MCP was not found on the basolateral surface as reported. Contrary to the gradually increasing plasma level of amylase and lipase, expression of complement activation regulators decreased after SAP model was set up. At the same time, the severity of pancreatic necrosis was enhanced.A strong negative correlation was found between the expression of MCP, DAF, CD59 in pancreatic acinar cells and the severity of pancreatic necrosis (r = -0.748, -0.827,-0.723; P<0.01). In the second series of experiments,no matter when the treatment of IL-4 was given (before or after the induction of SAP model), the serum level of amylase or lipase Was decreased

  19. Immunohistochemical localization of pancreatic spasmolytic polypeptide (PSP) in the pig

    DEFF Research Database (Denmark)

    Raaberg, Lasse; Poulsen, Steen Seier; Thim, L;

    1992-01-01

    , PSP immunoreactivity was seen in some of the cells in the epithelium of the crypts of Lieberkühn. A peptide chromatographically identical to highly purified PSP was identified in pancreas and stomach extracts. Thus epithelial cells in all parts of the stomach and small intestine contribute......Pancreatic spasmolytic polypeptide (PSP) is a peptide that is isolated from the porcine pancreas and that affects intestinal motility and growth of intestinal tumour cells in vitro. The peptide was recently demonstrated to be present in large amounts in pancreatic juice. The cellular origin...... of the peptide, however, is largely unclarified and the localization was therefore studied of PSP in pigs using immunohistochemistry. Positive immunoreactions were seen in the pancreas, the stomach, the duodenum, the jejunum and the ileum. In the pancreas, the PSP immunoreaction was seen in all acinar cells...

  20. Formation of salivary acinar cell spheroids in vitro above a polyvinyl alcohol-coated surface.

    Science.gov (United States)

    Chen, Min-Huey; Chen, Yi-Jane; Liao, Chih-Chen; Chan, Yen-Hui; Lin, Chia-Yung; Chen, Rung-Shu; Young, Tai-Hong

    2009-09-15

    Tissue engineering of salivary glands offers the potential for future use in the treatment of patients with salivary hypofunction. Biocompatible materials that promote acinar cell aggregation and function in vitro are an essential part of salivary gland tissue engineering. In this study, rat parotid acinar cells assembled into three-dimensional aggregates above the polyvinyl alcohol (PVA)-coated surface. These aggregates developed compact acinar cell spheroids resembling in vivo physiological condition, which were different from the traditional monolayered morphology in vitro. Cells remained viable and with better functional activity in response to acetylcholine in the spheroids and could form monolayered acinar cells when they were reinoculated on tissue culture polystyrene wells. To interpret the phenomenon further, we proposed that the formation of acinar cell spheroids on the PVA is mediated by a balance between two competing forces: the interactions of cell-PVA and cell-cell. This study demonstrated the formation of functional cell spheroids above a PVA-coated surface may provide an in vitro system for investigating cell behaviors for tissue engineering of artificial salivary gland.

  1. Zebrafish reporter lines reveal in vivo signaling pathway activities involved in pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Marco Schiavone

    2014-07-01

    Full Text Available Pancreatic adenocarcinoma, one of the worst malignancies of the exocrine pancreas, is a solid tumor with increasing incidence and mortality in industrialized countries. This condition is usually driven by oncogenic KRAS point mutations and evolves into a highly aggressive metastatic carcinoma due to secondary gene mutations and unbalanced expression of genes involved in the specific signaling pathways. To examine in vivo the effects of KRASG12D during pancreatic cancer progression and time correlation with cancer signaling pathway activities, we have generated a zebrafish model of pancreatic adenocarcinoma in which eGFP-KRASG12D expression was specifically driven to the pancreatic tissue by using the GAL4/UAS conditional expression system. Outcrossing the inducible oncogenic KRASG12D line with transgenic zebrafish reporters, harboring specific signaling responsive elements of transcriptional effectors, we were able to follow TGFβ, Notch, Bmp and Shh activities during tumor development. Zebrafish transgenic lines expressing eGFP-KRASG12D showed normal exocrine pancreas development until 3 weeks post fertilization (wpf. From 4 to 24 wpf we observed several degrees of acinar lesions, characterized by an increase in mesenchymal cells and mixed acinar/ductal features, followed by progressive bowel and liver infiltrations and, finally, highly aggressive carcinoma. Moreover, live imaging analysis of the exocrine pancreatic tissue revealed an increasing number of KRAS-positive cells and progressive activation of TGFβ and Notch pathways. Increase in TGFβ, following KRASG12D activation, was confirmed in a concomitant model of medulloblastoma (MDB. Notch and Shh signaling activities during tumor onset were different between MDB and pancreatic adenocarcinoma, indicating a tissue-specific regulation of cell signaling pathways. Moreover, our results show that a living model of pancreatic adenocarcinoma joined with cell signaling reporters is a suitable

  2. ERK activation is required for CCK-mediated pancreatic adaptive growth in mice.

    Science.gov (United States)

    Holtz, Bryan J; Lodewyk, Kevin B; Sebolt-Leopold, Judith S; Ernst, Stephen A; Williams, John A

    2014-10-01

    High levels of cholecystokinin (CCK) can stimulate pancreatic adaptive growth in which mature acinar cells divide, leading to enhanced pancreatic mass with parallel increases in protein, DNA, RNA, and digestive enzyme content. Prolonged release of CCK can be induced by feeding trypsin inhibitor (TI) to disrupt normal feedback control. This leads to exocrine growth in a CCK-dependent manner. The extracellular signal-related kinase (ERK) pathway regulates many proliferative processes in various tissues and disease models. The aim of this study was to evaluate the role of ERK signaling in pancreatic adaptive growth using the MEK inhibitors PD-0325901 and trametinib (GSK-1120212). It was determined that PD-0325901 given two times daily by gavage or mixed into powdered chow was an effective and specific inhibitor of ERK signaling in vivo. TI-containing chow led to a robust increase in pancreatic mass, protein, DNA, and RNA content. This pancreatic adaptive growth was blocked in mice fed chow containing the MEK inhibitors. PD-0325901 blocked TI-induced ERK-regulated early response genes, cell-cycle proteins, and mitogenesis by acinar cells. It was determined that ERK signaling is necessary for the initiation of pancreatic adaptive growth but not necessary to maintain it. PD-0325901 blocked adaptive growth when given before cell-cycle initiation but not after mitogenesis had been established. Furthermore, GSK-1120212, a chemically distinct inhibitor of the ERK pathway that is now approved for clinical use, inhibited growth similar to PD-0325901. These data demonstrate that the ERK pathway is required for CCK-stimulated pancreatic adaptive growth.

  3. Establishment of functional acinar-like cultures from human salivary glands.

    Science.gov (United States)

    Jang, S I; Ong, H L; Gallo, A; Liu, X; Illei, G; Alevizos, I

    2015-02-01

    Disorders of human salivary glands resulting from therapeutic radiation treatment for head and neck cancers or from the autoimmune disease Sjögren syndrome (SS) frequently result in the reduction or complete loss of saliva secretion. Such irreversible dysfunction of the salivary glands is due to the impairment of acinar cells, the major glandular cells of protein, salt secretion, and fluid movement. Availability of primary epithelial cells from human salivary gland tissue is critical for studying the underlying mechanisms of these irreversible disorders. We applied 2 culture system techniques on human minor salivary gland epithelial cells (phmSG) and optimized the growth conditions to achieve the maintenance of phmSG in an acinar-like phenotype. These phmSG cells exhibited progenitor cell markers (keratin 5 and nanog) as well as acinar-specific markers-namely, α-amylase, cystatin C, TMEM16A, and NKCC1. Importantly, with an increase of the calcium concentration in the growth medium, these phmSG cells were further promoted to acinar-like cells in vitro, as indicated by an increase in AQP5 expression. In addition, these phmSG cells also demonstrated functional calcium mobilization, formation of epithelial monolayer with high transepithelial electrical resistance (TER), and polarized secretion of α-amylase secretion after β-adrenergic receptor stimulation. Taken together, suitable growth conditions have been established to isolate and support culture of acinar-like cells from the human salivary gland. These primary epithelial cells can be useful for study of molecular mechanisms involved in regulating the function of acinar cells and in the loss of salivary gland function in patients.

  4. Hydrogen-rich saline ameliorates the severity of L-arginine-induced acute pancreatitis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Han; Sun, Yan Ping; Li, Yang [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China); Liu, Wen Wu [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China); Xiang, Hong Gang [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China); Fan, Lie Ying [Department of Clinical Laboratory, Shanghai East Hospital, Tong Ji University, Shanghai 200120 (China); Sun, Qiang [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China); Xu, Xin Yun [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China); Cai, Jian Mei [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China); Ruan, Can Ping; Su, Ning; Yan, Rong Lin [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China); Sun, Xue Jun, E-mail: sunxjk@hotmail.com [Department of Diving Medicine, Faculty of Naval Medicine, Second Military Medical University, Shanghai 200433 (China); Wang, Qiang, E-mail: wang2929@hotmail.com [Department of General Surgery, Shanghai Chang Zheng Hospital, Second Military Medical University, Shanghai 200003 (China)

    2010-03-05

    Molecular hydrogen, which reacts with the hydroxyl radical, has been considered as a novel antioxidant. Here, we evaluated the protective effects of hydrogen-rich saline on the L-arginine (L-Arg)-induced acute pancreatitis (AP). AP was induced in Sprague-Dawley rats by giving two intraperitoneal injections of L-Arg, each at concentrations of 250 mg/100 g body weight, with an interval of 1 h. Hydrogen-rich saline (>0.6 mM, 6 ml/kg) or saline (6 ml/kg) was administered, respectively, via tail vein 15 min after each L-Arg administration. Severity of AP was assessed by analysis of serum amylase activity, pancreatic water content and histology. Samples of pancreas were taken for measuring malondialdehyde and myeloperoxidase. Apoptosis in pancreatic acinar cell was determined with terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling technique (TUNEL). Expression of proliferating cell nuclear antigen (PCNA) and nuclear factor kappa B (NF-{kappa}B) were detected with immunohistochemistry. Hydrogen-rich saline treatment significantly attenuated the severity of L-Arg-induced AP by ameliorating the increased serum amylase activity, inhibiting neutrophil infiltration, lipid oxidation and pancreatic tissue edema. Moreover, hydrogen-rich saline treatment could promote acinar cell proliferation, inhibit apoptosis and NF-{kappa}B activation. These results indicate that hydrogen treatment has a protective effect against AP, and the effect is possibly due to its ability to inhibit oxidative stress, apoptosis, NF-{kappa}B activation and to promote acinar cell proliferation.

  5. Effect of nicotine on exocytotic pancreatic secretory response: role of calcium signaling

    Directory of Open Access Journals (Sweden)

    Chowdhury Parimal

    2013-01-01

    Full Text Available Abstract Background Nicotine is a risk factor for pancreatitis resulting in loss of pancreatic enzyme secretion. The aim of this study was to evaluate the mechanisms of nicotine-induced secretory response measured in primary pancreatic acinar cells isolated from Male Sprague Dawley rats. The study examines the role of calcium signaling in the mechanism of the enhanced secretory response observed with nicotine exposure. Methods Isolated and purified pancreatic acinar cells were subjected to a nicotine exposure at a dose of 100 μM for 6 minutes and then stimulated with cholecystokinin (CCK for 30 min. The cell’s secretory response was measured by the percent of amylase released from the cells in the incubation medium Calcium receptor antagonists, inositol trisphosphate (IP3 receptor blockers, mitogen activated protein kinase inhibitors and specific nicotinic receptor antagonists were used to confirm the involvement of calcium in this process. Results Nicotine exposure induced enhanced secretory response in primary cells. These responses remained unaffected by mitogen activated protein kinases (MAPK’s inhibitors. The effects, however, have been completely abolished by nicotinic receptor antagonist, calcium channel receptor antagonists and inositol trisphosphate (IP3 receptor blockers. Conclusions The data suggest that calcium activated events regulating the exocytotic secretion are affected by nicotine as shown by enhanced functional response which is inhibited by specific antagonists… The results implicate the role of nicotine in the mobilization of both intra- and extracellular calcium in the regulation of stimulus-secretory response of enzyme secretion in this cell system. We conclude that nicotine plays an important role in promoting enhanced calcium levels inside the acinar cell.

  6. Ny klassifikation af pancreatitis acuta

    DEFF Research Database (Denmark)

    Hansen, Benny Østerbye; Schmidt, Palle Nordblad

    2011-01-01

    The course of acute pancreatitis is in the initial phase dominated by a systemic inflammatory response, later by local complications. A new classification defines three specific types of pancreatitis: 1) interstitial oedematous pancreatitis and 2) necrotizing pancreatitis with pancreatic...

  7. Pancreatic pseudocyst

    Institute of Scientific and Technical Information of China (English)

    Samir Habashi; Peter V Draganov

    2009-01-01

    Pancreatic pseudocysts are complications of acute or chronic pancreatitis. Initial diagnosis is accomplished most often by cross-sectional imaging. Endoscopic ultrasound with fine needle aspiration has become the preferred test to help distinguish pseudocyst from other cystic lesions of the pancreas. Most pseudocysts resolve spontaneously with supportive care. The size of the pseudocyst and the length of time the cyst has been present are poor predictors for the potential of pseudocyst resolution or complications, but in general, larger cysts are more likely to be symptomatic or cause complications. The main two indications for some type of invasive drainage procedure are persistent patient symptoms or the presence of complications (infection, gastric outlet or biliary obstruction, bleeding). Three different strategies for pancreatic pseudocysts drainage are available: endoscopic (transpapillary or transmural) drainage, percutaneous catheter drainage, or open surgery. To date, no prospective controlled studies have compared directly these approaches. As a result, the management varies based on local expertise, but in general, endoscopic drainage is becoming the preferred approach because it is less invasive than surgery, avoids the need for external drain, and has a high long-term success rate. A tailored therapeutic approach taking into consideration patient preferences and involving multidisciplinary team of therapeutic endoscopist, interventional radiologist and pancreatic surgeon should be considered in all cases.

  8. ATP release, generation and hydrolysis in exocrine pancreatic duct cells.

    Science.gov (United States)

    Kowal, J M; Yegutkin, G G; Novak, I

    2015-12-01

    Extracellular adenosine triphosphate (ATP) regulates pancreatic duct function via P2Y and P2X receptors. It is well known that ATP is released from upstream pancreatic acinar cells. The ATP homeostasis in pancreatic ducts, which secrete bicarbonate-rich fluid, has not yet been examined. First, our aim was to reveal whether pancreatic duct cells release ATP locally and whether they enzymatically modify extracellular nucleotides/sides. Second, we wished to explore which physiological and pathophysiological factors may be important in these processes. Using a human pancreatic duct cell line, Capan-1, and online luminescence measurement, we detected fast ATP release in response to pH changes, bile acid, mechanical stress and hypo-osmotic stress. ATP release following hypo-osmotic stress was sensitive to drugs affecting exocytosis, pannexin-1, connexins, maxi-anion channels and transient receptor potential cation channel subfamily V member 4 (TRPV4) channels, and corresponding transcripts were expressed in duct cells. Direct stimulation of intracellular Ca(2+) and cAMP signalling and ethanol application had negligible effects on ATP release. The released ATP was sequentially dephosphorylated through ecto-nucleoside triphosphate diphosphohydrolase (NTPDase2) and ecto-5'-nucleotidase/CD73 reactions, with respective generation of adenosine diphosphate (ADP) and adenosine and their maintenance in the extracellular medium at basal levels. In addition, Capan-1 cells express counteracting adenylate kinase (AK1) and nucleoside diphosphate kinase (NDPK) enzymes (NME1, 2), which contribute to metabolism and regeneration of extracellular ATP and other nucleotides (ADP, uridine diphosphate (UDP) and uridine triphosphate (UTP)). In conclusion, we illustrate a complex regulation of extracellular purine homeostasis in a pancreatic duct cell model involving: ATP release by several mechanisms and subsequent nucleotide breakdown and ATP regeneration via counteracting nucleotide

  9. ATP release, generation and hydrolysis in exocrine pancreatic duct cells.

    Science.gov (United States)

    Kowal, J M; Yegutkin, G G; Novak, I

    2015-12-01

    Extracellular adenosine triphosphate (ATP) regulates pancreatic duct function via P2Y and P2X receptors. It is well known that ATP is released from upstream pancreatic acinar cells. The ATP homeostasis in pancreatic ducts, which secrete bicarbonate-rich fluid, has not yet been examined. First, our aim was to reveal whether pancreatic duct cells release ATP locally and whether they enzymatically modify extracellular nucleotides/sides. Second, we wished to explore which physiological and pathophysiological factors may be important in these processes. Using a human pancreatic duct cell line, Capan-1, and online luminescence measurement, we detected fast ATP release in response to pH changes, bile acid, mechanical stress and hypo-osmotic stress. ATP release following hypo-osmotic stress was sensitive to drugs affecting exocytosis, pannexin-1, connexins, maxi-anion channels and transient receptor potential cation channel subfamily V member 4 (TRPV4) channels, and corresponding transcripts were expressed in duct cells. Direct stimulation of intracellular Ca(2+) and cAMP signalling and ethanol application had negligible effects on ATP release. The released ATP was sequentially dephosphorylated through ecto-nucleoside triphosphate diphosphohydrolase (NTPDase2) and ecto-5'-nucleotidase/CD73 reactions, with respective generation of adenosine diphosphate (ADP) and adenosine and their maintenance in the extracellular medium at basal levels. In addition, Capan-1 cells express counteracting adenylate kinase (AK1) and nucleoside diphosphate kinase (NDPK) enzymes (NME1, 2), which contribute to metabolism and regeneration of extracellular ATP and other nucleotides (ADP, uridine diphosphate (UDP) and uridine triphosphate (UTP)). In conclusion, we illustrate a complex regulation of extracellular purine homeostasis in a pancreatic duct cell model involving: ATP release by several mechanisms and subsequent nucleotide breakdown and ATP regeneration via counteracting nucleotide

  10. Phenotypic changes in mouse pancreatic stellate cell Ca2+ signaling events following activation in culture and in a disease model of pancreatitis.

    Science.gov (United States)

    Won, Jong Hak; Zhang, Yu; Ji, Baoan; Logsdon, Craig D; Yule, David I

    2011-02-01

    The specific characteristics of intracellular Ca 2+ signaling and the downstream consequences of these events were investigated in mouse pancreatic stellate cells (PSC) in culture and in situ using multiphoton microscopy in pancreatic lobules. PSC undergo a phenotypic transformation from a quiescent state to a myofibroblast-like phenotype in culture. This is believed to parallel the induction of an activated state observed in pancreatic disease such as chronic pancreatitis and pancreatic cancer. By day 7 in culture, the complement of cell surface receptors coupled to intracellular Ca 2+ signaling was shown to be markedly altered. Specifically, protease-activated receptors (PAR) 1 and 2, responsive to thrombin and trypsin, respectively, and platelet-derived growth factor (PDGF) receptors were expressed only in activated PSC (aPSC). PAR-1, ATP, and PDGF receptor activation resulted in prominent nuclear Ca 2+ signals. Nuclear Ca 2+ signals and aPSC proliferation were abolished by expression of parvalbumin targeted to the nucleus. In pancreatic lobules, PSC responded to agonists consistent with the presence of only quiescent PSC. aPSC were observed following induction of experimental pancreatitis. In contrast, in a mouse model of pancreatic disease harboring elevated K-Ras activity in acinar cells, aPSC were present under control conditions and their number greatly increased following induction of pancreatitis. These data are consistent with nuclear Ca 2+ signaling generated by agents such as trypsin and thrombin, likely present in the pancreas in disease states, resulting in proliferation of "primed" aPSC to contribute to the severity of pancreatic disease.

  11. Is Pancreatic Cancer Hereditary?

    Science.gov (United States)

    ... Board Patient Education / Basics of Pancreatic Cancer Is pancreatic cancer hereditary? Cancer of the pancreas is a genetic ... found in cigarette smoke. The genetics of hereditary pancreatic cancer is a focus of research at Johns Hopkins. ...

  12. Pancreatic Islet Transplantation

    Science.gov (United States)

    ... Diabetes, Gum Disease, and Other Dental Problems Diabetic Eye Disease Diabetes and Pregnancy Financial Help for Diabetes Care Diabetes Statistics Pancreatic Islet Transplantation What are pancreatic islets? Pancreatic islets, also called ...

  13. Pancreatic tuberculosis masquerading as pancreatic serous cystadenoma

    Institute of Scientific and Technical Information of China (English)

    Seung Goun Hong; Jae Seon Kim; Moon Kyung Joo; Kwang Gyun Lee; Key Hyeon Kim; Cho Rong Oh; Jong-Jae Park; Young-Tae Bak

    2009-01-01

    Solitary pancreatic involvement of tuberculosis is rare,especially in an immunocompetent individual, and it may be misdiagnosed as pancreatic cystic neoplasms.Pancreatic cystic neoplasms are being identified in increasing numbers, probably because of the frequent use of radiology and advances in endoscopic techniques.However, they are composed of a variety of neoplasms with a wide range of malignant potential,and it is often difficult to differentiate pancreatic tuberculosis mimicking cystic neoplasms from benign or malignant pancreatic cystic neoplasms. Non-surgical diagnosis of pancreatic tuberculosis is inconclusive and continues to be a challenge in many cases. If so,then laparotomy should be employed to establish the diagnosis. Therefore, pancreatic tuberculosis should be kept in mind during the differential diagnosis of solitary cystic masses in the pancreas. We report a patient who had solitary pancreatic tuberculosis masquerading as pancreatic serous cystadenoma.

  14. Hyperlipidemia intensifies cerulein-induced acute pancreatitis associated with activation of protein kinase C in rats

    Institute of Scientific and Technical Information of China (English)

    Ya-Jun Wang; Jia-Bang Sun; Fei Li; Shu-Wen Zhang

    2006-01-01

    AIM: To investigate the effects of hyperlipidemia on acute pancreatitis (AP) and the possible mechanisms.METHODS: Rat models of hyperlipidemia and AP were established by Triton WR1339 and cerulein respectively.Human albumin was used to treat AP complicated by hyperlipidemia. In each group, we compared the histological score, volume of ascites, ratio of pancreatic wet/dry weight, serum amylase (AMY) and pancreatic acinar cell apoptosis. The level of protein kinase C (PKC) membrane translocation in pancreatic tissue was detected by Western blot.RESULTS: In the hyperlipidemia model established by Triton WR1339, triglyceride (TG) increased remarkably and reached its peak 6 h after injection, and most rats developed mild acute pancreatitis. Histological score, volume of ascites, ratio of wet/dry weight and serum AMY in AP animals with hyperlipidemia were obviously higher than those in AP animals (P <0.05) and decreased after albumin therapy but not significantly (P > 0.05). Apoptotic cells detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) increased in AP animals with hyperlipidemia and did not change distinctly after albumin therapy. PKC membrane translocation level increased in AP animals with hyperlipidemia and decreased remarkably after albumin therapy (P < 0.05).CONCLUSION: Hyperlipidemia may induce AP or intensify pancreatic injury. Albumin therapy can not alleviate pancreatic lesion effectively. PKC activation may be one mechanism by which AP is intensified by hyperlipidemia.

  15. Role of Biomarkers in Diagnosis and Prognostic Evaluation of Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Susanta Meher

    2015-01-01

    Full Text Available Acute pancreatitis is a potentially life threatening disease. The spectrum of severity of the illness ranges from mild self-limiting disease to a highly fatal severe necrotizing pancreatitis. Despite intensive research and improved patient care, overall mortality still remains high, reaching up to 30–40% in cases with infected pancreatic necrosis. Although little is known about the exact pathogenesis, it has been widely accepted that premature activation of digestive enzymes within the pancreatic acinar cell is the trigger that leads to autodigestion of pancreatic tissue which is followed by infiltration and activation of leukocytes. Extensive research has been done over the past few decades regarding their role in diagnosis and prognostic evaluation of severe acute pancreatitis. Although many standalone biochemical markers have been studied for early assessment of severity, C-reactive protein still remains the most frequently used along with Interleukin-6. In this review we have discussed briefly the pathogenesis and the role of different biochemical markers in the diagnosis and severity evaluation in acute pancreatitis.

  16. Glucagon-like peptide-1 receptor agonists increase pancreatic mass by induction of protein synthesis.

    Science.gov (United States)

    Koehler, Jacqueline A; Baggio, Laurie L; Cao, Xiemin; Abdulla, Tahmid; Campbell, Jonathan E; Secher, Thomas; Jelsing, Jacob; Larsen, Brett; Drucker, Daniel J

    2015-03-01

    Glucagon-like peptide-1 (GLP-1) controls glucose homeostasis by regulating secretion of insulin and glucagon through a single GLP-1 receptor (GLP-1R). GLP-1R agonists also increase pancreatic weight in some preclinical studies through poorly understood mechanisms. Here we demonstrate that the increase in pancreatic weight following activation of GLP-1R signaling in mice reflects an increase in acinar cell mass, without changes in ductal compartments or β-cell mass. GLP-1R agonists did not increase pancreatic DNA content or the number of Ki67(+) cells in the exocrine compartment; however, pancreatic protein content was increased in mice treated with exendin-4 or liraglutide. The increased pancreatic mass and protein content was independent of cholecystokinin receptors, associated with a rapid increase in S6 phosphorylation, and mediated through the GLP-1R. Rapamycin abrogated the GLP-1R-dependent increase in pancreatic mass but had no effect on the robust induction of Reg3α and Reg3β gene expression. Mass spectrometry analysis identified GLP-1R-dependent upregulation of Reg family members, as well as proteins important for translation and export, including Fam129a, eIF4a1, Wars, and Dmbt1. Hence, pharmacological GLP-1R activation induces protein synthesis, leading to increased pancreatic mass, independent of changes in DNA content or cell proliferation in mice.

  17. Autoimmune Pancreatitis: Etiology, Pathogenesis, Clinical Findings and Treatment. The Japanese Experience

    Directory of Open Access Journals (Sweden)

    Okazaki K

    2005-01-01

    Full Text Available A concept of "autoimmune pancreatitis" has recently been proposed. Computed tomography, magnetic resonance imaging or ultrasonography can demonstrate the diffusely enlarged pancreas with its so called "sausage-like" appearance. Hypergammaglobulinemia, increased serum levels of total IgG or IgG4, positive autoantibodies such as antinuclear antibody, anti-lactoferrin antibody, anti-CA-II antibody and rheumatoid factor have often been observed in patients with autoimmune pancreatitis. Microscopic findings have shown fibrotic changes involving infiltration of lymphocytes and plasmacytes, and often obliterative phlebitis in the pancreas. The major lymphocytes infiltrating the zone around the pancreatic duct were T cells producing IFN-g. HLA-DR was also expressed on the pancreatic duct and acinar cells as were lymphocytes. It is important to make the diagnosis of a diffusely enlarged pancreas based on clinical laboratory findings and pancreatic imaging such as narrowing pancreatogram. Laboratory data, pancreatic images and diabetes mellitus in most patients improved after steroid treatment.In conclusion, autoimmune pancreatitis appears to be a unique clinical entity.

  18. Impaired growth of pancreatic exocrine cells in transgenic mice expressing human activin βE subunit

    International Nuclear Information System (INIS)

    Activins, TGF-β superfamily members, have multiple functions in a variety of cells and tissues. Recently, additional activin β subunit genes, βC and βE, have been identified. To explore the role of activin E, we created transgenic mice overexpressing human activin βE subunit. There were pronounced differences in the pancreata of the transgenic animals as compared with their wild-type counterparts. Pancreatic weight, expressed relative to total body weight, was significantly reduced. Histologically, adipose replacement of acini in the exocrine pancreas was observed. There was a significant decrease in the number of PCNA-positive cells in the acinar cells, indicating reduced proliferation in the exocrine pancreas of the transgenic mice. However, quantitative pancreatic morphometry showed that the total number and mass of the islets of the transgenic mice were comparable with those of the nontransgenic control mice. Our findings suggest a role for activin E in regulating the proliferation of pancreatic exocrine cells

  19. Artesunate ameliorates severe acute pancreatitis (SAP) in rats by inhibiting expression of pro-inflammatory cytokines and Toll-like receptor 4.

    Science.gov (United States)

    Cen, Yanyan; Liu, Chao; Li, Xiaoli; Yan, Zifei; Kuang, Mei; Su, Yujie; Pan, Xichun; Qin, Rongxin; Liu, Xin; Zheng, Jiang; Zhou, Hong

    2016-09-01

    Severe acute pancreatitis (SAP) is a severe clinical condition with significant morbidity and mortality. Multiple organs dysfunction (MOD) is the leading cause of SAP-related death. The over-release of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α is the underlying mechanism of MOD; however, there is no effective agent against the inflammation. Herein, artesunate (AS) was found to increase the survival of SAP rats significantly when injected with 3.5% sodium taurocholate into the biliopancreatic duct in a retrograde direction, improving their pancreatic pathology and decreasing serum amylase and pancreatic lipase activities along with substantially reduced pancreatic IL-1β and IL-6 release. In vitro, AS-pretreatment strongly inhibited IL-1β and IL-6 release and their mRNA expressions in the pancreatic acinar cells treated with lipopolysaccharide (LPS) but exerted little effect on TNF-α release. Additionally, AS reduced the mRNA expressions of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) p65 as well as their protein expressions in the pancreatic acinar cells. In conclusion, our results demonstrated that AS could significantly protect SAP rats, and this protection was related to the reduction of digestive enzyme activities and pro-inflammatory cytokine expressions via inhibition of TLR4/NF-κB signaling pathway. Therefore, AS may be considered as a potential therapeutic agent against SAP.

  20. Artesunate ameliorates severe acute pancreatitis (SAP) in rats by inhibiting expression of pro-inflammatory cytokines and Toll-like receptor 4.

    Science.gov (United States)

    Cen, Yanyan; Liu, Chao; Li, Xiaoli; Yan, Zifei; Kuang, Mei; Su, Yujie; Pan, Xichun; Qin, Rongxin; Liu, Xin; Zheng, Jiang; Zhou, Hong

    2016-09-01

    Severe acute pancreatitis (SAP) is a severe clinical condition with significant morbidity and mortality. Multiple organs dysfunction (MOD) is the leading cause of SAP-related death. The over-release of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α is the underlying mechanism of MOD; however, there is no effective agent against the inflammation. Herein, artesunate (AS) was found to increase the survival of SAP rats significantly when injected with 3.5% sodium taurocholate into the biliopancreatic duct in a retrograde direction, improving their pancreatic pathology and decreasing serum amylase and pancreatic lipase activities along with substantially reduced pancreatic IL-1β and IL-6 release. In vitro, AS-pretreatment strongly inhibited IL-1β and IL-6 release and their mRNA expressions in the pancreatic acinar cells treated with lipopolysaccharide (LPS) but exerted little effect on TNF-α release. Additionally, AS reduced the mRNA expressions of Toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) p65 as well as their protein expressions in the pancreatic acinar cells. In conclusion, our results demonstrated that AS could significantly protect SAP rats, and this protection was related to the reduction of digestive enzyme activities and pro-inflammatory cytokine expressions via inhibition of TLR4/NF-κB signaling pathway. Therefore, AS may be considered as a potential therapeutic agent against SAP. PMID:27318790

  1. Effects of Oxidative Alcohol Metabolism on the Mitochondrial Permeability Transition Pore and Necrosis in a Mouse Model of Alcoholic Pancreatitis

    Science.gov (United States)

    SHALBUEVA, NATALIA; MARENINOVA, OLGA A.; GERLOFF, ANDREAS; YUAN, JINGZHEN; WALDRON, RICHARD T.; PANDOL, STEPHEN J.; GUKOVSKAYA, ANNA S.

    2013-01-01

    BACKGROUND & AIMS Opening of the mitochondrial permeability transition pore (MPTP) causes loss of the mitochondrial membrane potential (ΔΨm) and, ultimately, adenosine triphosphate depletion and necrosis. Cells deficient in cyclophilin D (CypD), a component of the MPTP, are resistant to MPTP opening, loss of ΔΨm, and necrosis. Alcohol abuse is a major risk factor for pancreatitis and is believed to sensitize the pancreas to stressors, by poorly understood mechanisms. We investigated the effects of ethanol on the pancreatic MPTP, the mechanisms of these effects, and their role in pancreatitis. METHODS We measured ΔΨm in mouse pancreatic acinar cells incubated with ethanol alone and in combination with physiologic and pathologic concentrations of cholecystokinin-8 (CCK). To examine the role of MPTP, we used ex vivo and in vivo models of pancreatitis, induced in wild-type and CypD−/− mice by a combination of ethanol and CCK. RESULTS Ethanol reduced basal ΔΨm and converted a transient depolarization, induced by physiologic concentrations of CCK, into a sustained decrease in ΔΨm, resulting in reduced cellular adenosine triphosphate and increased necrosis. The effects of ethanol and CCK were mediated by MPTP because they were not observed in CypD−/− acinar cells. Ethanol and CCK activated MPTP through different mechanisms— ethanol by reducing the ratio of oxidized nicotinamide adenine dinucleotide to reduced nicotinamide adenine dinucleotide, as a result of oxidative metabolism, and CCK by increasing cytosolic Ca2+. CypD−/− mice developed a less-severe form of pancreatitis after administration of ethanol and CCK. CONCLUSIONS Oxidative metabolism of ethanol sensitizes pancreatic mitochondria to activate MPTP, leading to mitochondrial failure; this makes the pancreas susceptible to necrotizing pancreatitis. PMID:23103769

  2. The pattern of fibrosis in the acinar zone 3 areas in early alcoholic liver disease

    DEFF Research Database (Denmark)

    Junge, Jette; Horn, T; Vyberg, M;

    1991-01-01

    The degree of fibrosis and the pattern of collagen distribution in the acinar zone 3, as well as the thickness of the terminal hepatic vein walls (THV) were analyzed in 48 consecutive liver needle biopsies from 48 alcoholics with preserved liver architecture. The fibrosis occurred to more or less...

  3. Ectrodactyly and Lethal Pulmonary Acinar Dysplasia Associated with Homozygous FGFR2 Mutations Identified by Exome Sequencing.

    Science.gov (United States)

    Barnett, Christopher P; Nataren, Nathalie J; Klingler-Hoffmann, Manuela; Schwarz, Quenten; Chong, Chan-Eng; Lee, Young K; Bruno, Damien L; Lipsett, Jill; McPhee, Andrew J; Schreiber, Andreas W; Feng, Jinghua; Hahn, Christopher N; Scott, Hamish S

    2016-09-01

    Ectrodactyly/split hand-foot malformation is genetically heterogeneous with more than 100 syndromic associations. Acinar dysplasia is a rare congenital lung lesion of unknown etiology, which is frequently lethal postnatally. To date, there have been no reports of combinations of these two phenotypes. Here, we present an infant from a consanguineous union with both ectrodactyly and autopsy confirmed acinar dysplasia. SNP array and whole-exome sequencing analyses of the affected infant identified a novel homozygous Fibroblast Growth Factor Receptor 2 (FGFR2) missense mutation (p.R255Q) in the IgIII domain (D3). Expression studies of Fgfr2 in development show localization to the affected limbs and organs. Molecular modeling and genetic and functional assays support that this mutation is at least a partial loss-of-function mutation, and contributes to ectrodactyly and acinar dysplasia only in homozygosity, unlike previously reported heterozygous activating FGFR2 mutations that cause Crouzon, Apert, and Pfeiffer syndromes. This is the first report of mutations in a human disease with ectrodactyly with pulmonary acinar dysplasia and, as such, homozygous loss-of-function FGFR2 mutations represent a unique syndrome. PMID:27323706

  4. Acinar autolysis and mucous extravasation in human sublingual glands: a microscopic postmortem study

    Directory of Open Access Journals (Sweden)

    Luciana Reis AZEVEDO-ALANIS

    2015-10-01

    Full Text Available Although some morphological investigations on aged human sublingual glands (HSG found eventual phenomena identified as autolysis and mucous extravasation, the exact meaning of these findings has not been elucidated.Objective The aim of this work is to investigate whether acinar autolysis and mucous extravasation are related to the aging process in human sublingual glands. We also speculate if autolytic changes may assist forensic pathologists in determining time of death.Material and Methods 186 cadavers’ glands were allocated to age groups: I (0–30 years; II (31–60, and III (61–90. Time and mode of death were also recorded. Acinar autolysis and mucous extravasation were classified as present or absent. Ultrastructural analysis was performed using transmission electron microscopy (TEM. Data were compared using Mann-Whitney U, Spearman’s correlation coefficient, Kruskal-Wallis, and Dunn tests (p<0.05.Results There was correlation between age and acinar autolysis (r=0.38; p=0.0001. However, there was no correlation between autolysis and time of death. No differences were observed between genders. TEM showed mucous and serous cells presenting nuclear and membrane alterations and mucous cells were more susceptible to autolysis.Conclusion Acinar autolysis occurred in all age groups and increased with age while mucous extravasation was rarely found. Both findings are independent. Autolysis degrees in HSG could not be used to determine time of death.

  5. Geometrical influence of pulmonary acinar models on respiratory flows and particle deposition

    Science.gov (United States)

    Hofemeier, Philipp; Sznitman, Josue

    2012-11-01

    Due to experimental challenges in assessing respiratory flows in the deep regions of the lungs, computational simulations are typically sought to quantify inhaled aerosol transport and deposition in the acinus. Most commonly, simulations are performed using generic geometries of alveoli, including spheres, toroids and polyhedra to mimic the acinar region. However, local respiratory flows and ensuing particle trajectories are anticipated to be highly influenced by the specific geometrical structures chosen. To date, geometrical influences have not yet been thoroughly quantified. Knowing beforehand how geometries affect acinar flows and particle transport is critical in translating simulated data to predictions of aerosol deposition in real lungs. Here, we conduct a systematic investigation on a number of generic acinar models. Simulations are conducted for simple alveolated airways featuring a selection of geometries. Deposition patterns and efficiencies are quantified both for massless particles, highlighting details of the local flow, and micron-scale aerosols. This latter group of particles represents an important class of inhaled aerosols known to reach and deposit in the acinus. Our work emphasizes the subtleties of acinar geometry in determining the fate of inhaled aerosols.

  6. Acinar autolysis and mucous extravasation in human sublingual glands: a microscopic postmortem study

    Science.gov (United States)

    AZEVEDO-ALANIS, Luciana Reis; TOLENTINO, Elen de Souza; de ASSIS, Gerson Francisco; CESTARI, Tânia Mary; LARA, Vanessa Soares; DAMANTE, José Humberto

    2015-01-01

    Although some morphological investigations on aged human sublingual glands (HSG) found eventual phenomena identified as autolysis and mucous extravasation, the exact meaning of these findings has not been elucidated. Objective The aim of this work is to investigate whether acinar autolysis and mucous extravasation are related to the aging process in human sublingual glands. We also speculate if autolytic changes may assist forensic pathologists in determining time of death. Material and Methods 186 cadavers’ glands were allocated to age groups: I (0–30 years); II (31–60), and III (61–90). Time and mode of death were also recorded. Acinar autolysis and mucous extravasation were classified as present or absent. Ultrastructural analysis was performed using transmission electron microscopy (TEM). Data were compared using Mann-Whitney U, Spearman’s correlation coefficient, Kruskal-Wallis, and Dunn tests (p<0.05). Results There was correlation between age and acinar autolysis (r=0.38; p=0.0001). However, there was no correlation between autolysis and time of death. No differences were observed between genders. TEM showed mucous and serous cells presenting nuclear and membrane alterations and mucous cells were more susceptible to autolysis. Conclusion Acinar autolysis occurred in all age groups and increased with age while mucous extravasation was rarely found. Both findings are independent. Autolysis degrees in HSG could not be used to determine time of death. PMID:26537715

  7. ERCP in acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Jijo V Cherian; Joye Varghese Selvaraj; Rajesh Natrayan; Jayanthi Venkataraman

    2007-01-01

    BACKGROUND:The role of endoscopic retrograde cholangiopancreatography (ERCP) in the management of acute pancreatitis has evolved over years since its introduction in 1968. Its importance in diagnosing the etiology of pancreatitis has steadily declined with the advent of less invasive diagnostic tools. The therapeutic implications of ERCP in acute pancreatitis are many fold and are directed towards management of known etiological factors or its related complications. This article highlights the current status of ERCP in acute pancreatitis. DATA SOURCES:An English literature search using PubMed database was conducted on ERCP in acute pancreatitis, the etiologies and complications of pancreatitis amenable to endotherapy and other related subjects, which were reviewed. RESULTS: ERCP serves as a primary therapeutic modality for management of biliary pancreatitis in speciifc situations, pancreatitis due to microlithiasis, speciifc types of sphincter of Oddi dysfunction, pancreas divisum, ascariasis and malignancy. In recurrent acute pancreatitis and smoldering pancreatitis it has a deifnite therapeutic utility. Complications of acute pancreatitis including pancreatic-duct disruptions or leaks, benign pancreatic-lfuid collections and pancreatic necrosis can be beneifcially dealt with. Intraductal ultrasound and pancreatoscopy during ERCP are useful in detecting pancreatic malignancy. CONCLUSIONS:The role of ERCP in acute pancreatitis is predominantly therapeutic and occasionally diagnostic. Its role in the management continues to evolve and advanced invasive procedures should be undertaken only in centers dedicated to pancreatic care.

  8. Hypoxic vasoconstriction of partial muscular intra-acinar pulmonary arteries in murine precision cut lung slices

    Directory of Open Access Journals (Sweden)

    Goldenberg Anna

    2006-06-01

    Full Text Available Abstract Background Acute alveolar hypoxia causes pulmonary vasoconstriction (HPV which serves to match lung perfusion to ventilation. The underlying mechanisms are not fully resolved yet. The major vascular segment contributing to HPV, the intra-acinar artery, is mostly located in that part of the lung that cannot be selectively reached by the presently available techniques, e.g. hemodynamic studies of isolated perfused lungs, recordings from dissected proximal arterial segments or analysis of subpleural vessels. The aim of the present study was to establish a model which allows the investigation of HPV and its underlying mechanisms in small intra-acinar arteries. Methods Intra-acinar arteries of the mouse lung were studied in 200 μm thick precision-cut lung slices (PCLS. The organisation of the muscle coat of these vessels was characterized by α-smooth muscle actin immunohistochemistry. Basic features of intra-acinar HPV were characterized, and then the impact of reactive oxygen species (ROS scavengers, inhibitors of the respiratory chain and Krebs cycle metabolites was analysed. Results Intra-acinar arteries are equipped with a discontinuous spiral of α-smooth muscle actin-immunoreactive cells. They exhibit a monophasic HPV (medium gassed with 1% O2 that started to fade after 40 min and was lost after 80 min. This HPV, but not vasoconstriction induced by the thromboxane analogue U46619, was effectively blocked by nitro blue tetrazolium and diphenyleniodonium, indicating the involvement of ROS and flavoproteins. Inhibition of mitochondrial complexes II (3-nitropropionic acid, thenoyltrifluoroacetone and III (antimycin A specifically interfered with HPV, whereas blockade of complex IV (sodium azide unspecifically inhibited both HPV and U46619-induced constriction. Succinate blocked HPV whereas fumarate had minor effects on vasoconstriction. Conclusion This study establishes the first model for investigation of basic characteristics of HPV

  9. Framework for interpretation of trypsin-antitrypsin imbalance and genetic heterogeneity in pancreatitis

    Directory of Open Access Journals (Sweden)

    Kun Lin

    2015-01-01

    Full Text Available Early intracellular premature trypsinogen activation was interpreted as the key initiator of pancreatitis. When the balance in the homeostasis of trypsin and antitrypsin system is disequilibrated, elevated aggressive enzymes directly attack the pancreatic tissue, which leads to pancreatic destruction and inflammation. However, trypsin alone is not enough to cause complications in pancreatitis, which may play a crucial role in modulating signaling events in the initial phase of the disease. NFκB activation is the major inflammatory pathway involved in the occurrence and development of pancreatitis and it can be induced by intrapancreatic activation of trypsinogen. Synthesis of trypsinogen occurs in endoplasmic reticulum (ER, and ER stress is an important early acinar cell event. Components of ER stress response are known to be able to trigger cell death as well as NFκB signaling cascade. The strongest evidence supporting the trypsin-centered theory is that gene mutations, which lead to the generation of more trypsin, or reduce the activity of trypsin inhibitors or trypsin degradation, are associated with pancreatitis. Thus, trypsin–antitrypsin imbalance may be the first step leading to pancreatic autodigestion and inducing other pathways. Continued experimental studies are necessary to determine the specific relationships between trypsin–antitrypsin imbalance and genetic heterogeneity in pancreatitis. In this article, we review the latest advances that contributed to the understanding of the basic mechanisms behind the occurrence and development of pancreatitis with a focus on the interpretation of trypsin–antitrypsin imbalance and their relationships with other inflammation pathways. We additionally highlight genetic predispositions to pancreatitis and possible mechanisms associated with them.

  10. Metformin induced acute pancreatitis

    OpenAIRE

    Alsubaie, Sadeem; Almalki, Mussa H.

    2013-01-01

    Acute pancreatitis frequently presents with abdomen pain but may presents with various skin manifestations as rash and rarely, pancreatic panniculitis. Metformin, one of the most effective and valuable oral hypoglycemic agents in the biguanide class was linked to acute pancreatitis in few cases. Here, we report a case of metformin induce acute pancreatitis in young healthy man with normal renal function.

  11. Effect of biologically active fraction of Nardostachys jatamansi on cerulein-induced acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Gi-Sang Bae; Min-Sun Kim; Kyoung-Chel Park; Bon Soon Koo; Il-Joo Jo; Sun Bok Choi; Dong-Sung Lee

    2012-01-01

    AIM:TO determine if the fraction of Nardostachysjatamansi (NJ) has the potential to ameliorate the severity of acute pancreatitis (AP).METHODS:Mice were administered the biologically active fraction of NJ,i.e.,the 4th fraction (NJ4),intraperitoneally,and then injected with the stable cholecystokinin analogue cerulein hourly for 6 h.Six hours after the last cerulein injection,the pancreas,lung,and blood were harvested for morphological examination,measurement of cytokine expression,and examination of neutrophil infiltration.RESULTS:NJ4 administration attenuated the severity of AP and lung injury associated with AP.It also reduced cytokine production and neutrophil infiltration and resulted in the in vivo up-regulation of heme oxygenase-1 (HO-1).Furthermore,NJ4 and its biologically active fraction,N J4-2 inhibited the cerulein-induced death of acinar cells by inducing HO-1 in isolated pancreatic acinar cells.CONCLUSION:These results suggest that NJ4 may be a candidate fraction offering protection in AP and NJ4 might ameliorate the severity of pancreatitis by inducing HO-1 expression.

  12. One compound of saponins from Disocorea zingiberensis protected against experimental acute pancreatitis by preventing mitochondria-mediated necrosis

    Science.gov (United States)

    Zhang, Rui; Wen, Li; Shen, Yan; Shi, Na; Xing, Zhihua; Xia, Qing; Niu, Hai; Huang, Wen

    2016-01-01

    Acute pancreatitis (AP) is a painful inflammatory disorder of the exocrine pancreas, ranking as the most common gastrointestinal reasons for hospitalization with no specific therapy currently. Diosgenyl saponins extracted from natural products and diosgenin or its derivatives have been shown to exert anti-inflammatory effects in various diseases. However, the therapeutic effects of diosgenyl saponins from Dioscorea zingiberensis C. H. Wright in AP have not yet been determined. Five compounds were extracted and screened for taurocholate-induced necrosis in mouse pancreatic acinar cells. Particularly, 26-O-β-d-glucopyranosyl-3β, 22α, 26-trihydroxy-25(R)-furosta-5-en-3-O-[α-L-rhamnopyranosyl-(1 → 4)]-β-d-glucopyranoside (compound 1) exhibited the best protective effects with no toxicity observed. Next, we showed compound 1 concentration-dependently inhibited necrotic cell death pathway activation and 2.5 mM compound 1 also prevented the loss of mitochondrial membrane potential, adenosine triphosphate production, and reactive oxygen species generation in mouse pancreatic acinar cells. Finally, we showed compound 1 protected against three clinically representative murine models of AP and significantly improved pancreatitis-associated acute lung injury. These data provide in vitro and in vivo evidence that one compound of diosgenyl saponins can be potential treatment for AP. This study suggests natural saponins may serve as fruitful sources for exploring/identifying potential therapies for inflammatory diseases. PMID:27779235

  13. Complications of pancreatic surgery

    OpenAIRE

    Åke Andrén-Sandberg

    2011-01-01

    Many diseases, including pancreatitis benign tumors and cancer, may require pancreas surgery. Pancreatic resection can lead to a prolonged survival in pancreatic cancer and even a potential chance for cure. However, the pancreatic surgery can result in complications, and high postoperative morbidity rates are still presence. This article reviews the pancreatic abstracts of American Pancreas Club 2011, which involves the more common complications, their prevention and treatment.

  14. Biomarkers for pancreatic carcinogenesis

    OpenAIRE

    Hustinx, S.R.

    2007-01-01

    Pancreatic cancer is a devastating disease. Most pancreatic cancers (approximately 85%) are diagnosed at a late, incurable stage. The poor prognosis and late presentation of pancreatic cancer patients underscore the importance of early detection, which is the sine qua non for the fight against pancreatic cancer. It is hoped for the future that the understanding of genetic alterations will lead to the rapid discovery of an effective biomarker of pancreatic carcinogenesis. In this thesis we vis...

  15. Pancreatic transplantation

    Directory of Open Access Journals (Sweden)

    Åke Andrén-Sandberg

    2010-01-01

    Full Text Available A pancreas transplant is a surgical procedure to place a healthy pancreas from a donor into a patient whose pancreas no longer functions properly. Exocrine pancreas transplantation remains the standard treatment of choice for patients with diabetes mellitus complicated by end-stage renal disease. The use of pancreas transplantation for type 2 diabetes mellitus is an emerging concept. A pancreas transplant is often done in conjunction with a kidney transplant. Even if pancreas transplantation provides the best glycemic control option for diabetes mellitus, it is associated with significant morbidities related to infectious disease. The present article provides with a review of pancreatic transplantation.

  16. Protective Effect of Pretreatment with Acenocoumarol in Cerulein-Induced Acute Pancreatitis

    Science.gov (United States)

    Warzecha, Zygmunt; Sendur, Paweł; Ceranowicz, Piotr; Dembiński, Marcin; Cieszkowski, Jakub; Kuśnierz-Cabala, Beata; Olszanecki, Rafał; Tomaszewska, Romana; Ambroży, Tadeusz; Dembiński, Artur

    2016-01-01

    Coagulation is recognized as a key player in inflammatory and autoimmune diseases. The aim of the current research was to examine the effect of pretreatment with acenocoumarol on the development of acute pancreatitis (AP) evoked by cerulein. Methods: AP was induced in rats by cerulein administered intraperitoneally. Acenocoumarol (50, 100 or 150 µg/kg/dose/day) or saline were given once daily for seven days before AP induction. Results: In rats with AP, pretreatment with acenocoumarol administered at the dose of 50 or 100 µg/kg/dose/day improved pancreatic histology, reducing the degree of edema and inflammatory infiltration, and vacuolization of acinar cells. Moreover, pretreatment with acenocoumarol given at the dose of 50 or 100 µg/kg/dose/day reduced the AP-evoked increase in pancreatic weight, serum activity of amylase and lipase, and serum concentration of pro-inflammatory interleukin-1β, as well as ameliorated pancreatic DNA synthesis and pancreatic blood flow. In contrast, acenocoumarol given at the dose of 150 μg/kg/dose did not exhibit any protective effect against cerulein-induced pancreatitis. Conclusion: Low doses of acenocoumarol, given before induction of AP by cerulein, inhibit the development of that inflammation. PMID:27754317

  17. Pancreatic Cancer (Beyond the Basics)

    Science.gov (United States)

    ... Terms of Use ©2016 UpToDate, Inc. Patient information: Pancreatic cancer (Beyond the Basics) Author David P Ryan, MD ... pancreatic juice to the intestines. This type of pancreatic cancer, called "pancreatic ductal adenocarcinoma," is discussed in this ...

  18. Epiregulin is critical for the acinar cell regeneration of the submandibular gland in a mouse duct ligation model.

    Science.gov (United States)

    Nagai, Koichi; Arai, Hideo; Okudera, Michisato; Yamamura, Takashi; Oki, Hidero; Komiyama, Kazuo

    2014-05-01

    Acinar cell regeneration from tubular structures has been reported to occur in duct-deligated salivary glands. However, the detailed process of acinar cell regeneration has not been clarified. We have developed a mouse duct ligation model to clarify the mechanisms underlying acinar cell regeneration, and we analyzed the epidermal growth factor receptor (EGFR) and epidermal growth factor (EGF) ligands using the model. We studied these ligands expressions in the course of acinar cell regeneration using immunohistochemistry and RT-PCR methods. In the duct-ligated portion of the submandibular gland (SMG) that underwent atrophy, newly formed acinar cells were observed arising from the tubular structures after the release of the duct obstruction. The constitutive expression of EGFR was observed by immunohistochemistry in both the duct-ligated and duct-deligated animals as well as in normal controls. The EGFR phosphorylation detected on the tubular structures after duct ligation paralleled the acinar cell regeneration. RT-PCR showed an increase in the epiregulin and heparin-binding EGF levels from day 0 to day 3 after the release of the duct obstruction. The EGF level was increased only after day 7. In vitro, cultured cells isolated from ligated SMGs proliferated and produced EGF ligands following the addition of epiregulin to the culture medium. These findings suggest that the tubular structures localized in an atrophic gland are the source of acinar cell regeneration of the salivary gland. The induction of EGF ligands, in particular epiregulin, may play an important role in acinar cell regeneration in this model.

  19. Effect of early administration of exogenous basic fibroblast growth factor on acute edematous pancreatitis in rats

    Institute of Scientific and Technical Information of China (English)

    Qiang Yan; Xing Yao; Li-Cheng Dai; Guo-Lei Zhang; Jin-Liang Ping; Jian-Fang He; Chun-Fan Han

    2006-01-01

    AIM: To observe the therapeutic effect of early administration of exogenous Basic fibroblast growth factor (bFGF) on acute edematous pancreatitis (AEP) in rats.METHODS: Thirty male Sprague-Dawley rats were ran-domly divided into three (n = 10): normal control group (group Ⅰ), AEP group (group Ⅱ) and AEP with bFGF treatment group (group Ⅲ). AEP was induced by subcutaneous injection of cerulein (5.5 μg/kg and 7.5 μg/kg) at 1 h interval into rats of groups Ⅱ and Ⅲ. Three hours after induction of AEP, 100 μg/kg bFGF was administrated intraperitoneally for 1h to group Ⅲ rats. For test of DNA synthesis in acinar cells, 5-bromo-2'-deoxyuridine (BrdU) labeling solution was intraperitoneally injected into the rats of groups Ⅱ and Ⅲ 24 h after bFGF treatment. The changes in serum amylase, lipase, pancreatic tissue wet/dry ratio were detected.RESULTS: In bFGF treatment group, there was a significant decrease in the volume of serum amylase, lipase and the pancreatic wet/dry weight ratio(1383.0±94.6 U/L, 194.0 ± 43.6 U/L, 4.32 ± 0.32) compared to AEP group (3464 ± 223.7 U/L, 456 ±68.7 U/L, 6.89 ± 0.47) (P < 0.01), and no significant difference was found between bFGF treatment and control group (1289 ± 94.0 U/L, 171 ± 23.4 U/L, 4.12 ± 0.26, P > 0.05). The inflammatory changes such as interstitial edema, polymorphonuclear neutrophils (PMNs) and vacuolization were significantly ameliorated compared to AEP group (P < 0.01). A small number of BrdU-labeled nuclei were observed in acinar cells of AEP rats (1.8 ± 0.3 nuclei/microscopic field, n = 10) while diffuse BrdU-labeled nuclei were found in bFGF-treated rats (18.9 ± 1.4 nuclei/microscopic field, n = 10) (P < 0.01). Immunohistochemical study showed increased DNA synthesis in pancreatic acinar cells.CONCLUSION: Early administration of exogenous bFGF has significant therapeutic effect on cerulein-induced acute edematous pancreatitis in rats. Its mechanism is related to the amelioration of

  20. Glycosylations in demilunar and central acinar cells of the submandibular salivary gland of ferret investigated by lectin histochemistry.

    Science.gov (United States)

    Triantafyllou, Asterios; Fletcher, David; Scott, John

    2004-09-01

    'Resting' submandibular salivary glands obtained post-mortem from mature ferrets of both sexes were examined here. The binding patterns of labelled lectins applied to paraffin sections of tissue slivers fixed in an aldehyde-HgCl2 mixture and the effects of pretreatment procedures on the results were assessed lightmicroscopically. Lectins with affinity for terminal GalNAc residues (DBA, SBA) bound preferentially to demilunar acinar cells which were also strongly reactive with Fuc-directed UEA I. In contrast, lectins with affinity for neuraminic acid (SNA, WGA) bound to central acinar cells where consistent binding of DBA and SNA occurred only after neuraminidase digestion, and variation in the binding of UEA I was seen. The reactivities corresponded with the distribution of secretory granules, but staining in Golgi-like areas occurred in central acinar cells with PNA lectin. The results suggest that glycosylations are more advanced in central than demilunar acinar cells of the ferret submandibular gland. Possibly demilunar and central acinar cells reflect phenotypic changes of a single secretory cell, the 'central' acinar phenotype being influenced by incorporation of neuraminic acid in glycoprotein side chains and by increased Golgi activity.

  1. Salivary gland acinar cells regenerate functional glandular structures in modified hydrogels

    Science.gov (United States)

    Pradhan, Swati

    Xerostomia, a condition resulting from irradiation of the head and neck, affects over 40,000 cancer patients each year in the United States. Direct radiation damage of the acinar cells that secrete fluid and protein results in salivary gland hypofunction. Present medical management for xerostomia for patients treated for upper respiratory cancer is largely ineffective. Patients who have survived their terminal diagnosis are often left with a diminished quality of life and are unable to enjoy the simple pleasures of eating and drinking. This project aims to ultimately reduce human suffering by developing a functional implantable artificial salivary gland. The goal was to create an extracellular matrix (ECM) modified hyaluronic acid (HA) based hydrogel culture system that allows for the growth and differentiation of salivary acinar cells into functional acini-like structures capable of secreting large amounts of protein and fluid unidirectionally and to ultimately engineer a functional artificial salivary gland that can be implanted into an animal model. A tissue collection protocol was established and salivary gland tissue was obtained from patients undergoing head and neck surgery. The tissue specimen was assessed by histology and immunohistochemistry to establish the phenotype of normal salivary gland cells including the native basement membranes. Hematoxylin and eosin staining confirmed normal glandular tissue structures including intercalated ducts, striated ducts and acini. alpha-Amylase and periodic acid schiff stain, used for structures with a high proportion of carbohydrate macromolecules, preferentially stained acinar cells in the tissue. Intercalated and striated duct structures were identified using cytokeratins 19 and 7 staining. Myoepithelial cells positive for cytokeratin 14 were found wrapped around the serous and mucous acini. Tight junction components including ZO-1 and E-cadherin were present between both ductal and acinar cells. Ductal and acinar

  2. Autoimmune Pancreatitis: A Succinct Overview

    OpenAIRE

    Juan Putra; Xiaoying Liu

    2015-01-01

    Autoimmune pancreatitis is a rare type of chronic pancreatitis with characteristic clinical, radiologic, and histopathologic findings. Diagnosis of autoimmune pancreatitis is often challenging due to its low incidence and nonspecific clinical and radiologic findings. Patients with autoimmune pancreatitis and pancreatic cancer share similar clinical presentations, including obstructive jaundice, abdominal pain and weight loss. Due to these overlapping features, autoimmune pancreatitis patients...

  3. Functional differences in the acinar cells of the murine major salivary glands.

    Science.gov (United States)

    Kondo, Y; Nakamoto, T; Jaramillo, Y; Choi, S; Catalan, M A; Melvin, J E

    2015-05-01

    In humans, approximately 90% of saliva is secreted by the 3 major salivary glands: the parotid (PG), the submandibular (SMG), and the sublingual glands (SLG). Even though it is known that all 3 major salivary glands secrete saliva by a Cl(-)-dependent mechanism, salivary secretion rates differ greatly among these glands. The goal of this study was to gain insight into the properties of the ion-transporting pathways in acinar cells that might account for the differences among the major salivary glands. Pilocarpine-induced saliva was simultaneously collected in vivo from the 3 major salivary glands of mice. When normalized by gland weight, the amount of saliva secreted by the PG was more than 2-fold larger than that obtained from the SMG and SLG. At the cellular level, carbachol induced an increase in the intracellular [Ca(2+)] that was more than 2-fold larger in PG and SMG than in SLG acinar cells. Carbachol-stimulated Cl(-) efflux and the protein levels of the Ca(2+)-activated Cl(-) channel TMEM16A, the major apical Cl(-) efflux pathway in salivary acinar cells, were significantly greater in PG compared with SMG and SLG. In addition, we evaluated the transporter activity of the Na(+)-K(+)-2Cl(-) cotransporters (NKCC1) and anion exchangers (AE), the 2 primary basolateral Cl(-) uptake mechanisms in acinar cells. The SMG NKCC1 activity was about twice that of the PG and more than 12-fold greater than that of the SLG. AE activity was similar in PG and SLG, and both PG and SLG AE activity was about 2-fold larger than that of SMG. In summary, the salivation kinetics of the 3 major glands are distinct, and these differences can be explained by the unique functional properties of each gland related to Cl(-) movement, including the transporter activities of the Cl(-) uptake and efflux pathways, and intracellular Ca(2+) mobilization.

  4. Imaging of Acute Pancreatitis.

    Science.gov (United States)

    Thoeni, Ruedi F

    2015-11-01

    Acute pancreatitis is an acute inflammation of the pancreas. Several classification systems have been used in the past but were considered unsatisfactory. A revised Atlanta classification of acute pancreatitis was published that assessed the clinical course and severity of disease; divided acute pancreatitis into interstitial edematous pancreatitis and necrotizing pancreatitis; discerned an early phase (first week) from a late phase (after the first week); and focused on systemic inflammatory response syndrome and organ failure. This article focuses on the revised classification of acute pancreatitis, with emphasis on imaging features, particularly on newly-termed fluid collections and implications for the radiologist.

  5. Simultaneous determination of the content of serotonin, dopamine, noradrenaline and adrenaline in pancreatic islets isolated from fed and starved mice

    International Nuclear Information System (INIS)

    A highly sensitive double isotope method for the simultaneous determination of serotonin, dopamine, noradrenaline and adrenaline has been developed. Advantages and limitations of the method are discussed. The mentioned biogenic amines are all present in isolated pancreatic islet tissue from albino mice in concentrations ranging from approximately 5-30 μmol per kg wet weight (0.8-5 x 10-3 pmol/ng DNA). A somewhat higher content of these amines, especially dopamine, was found in pancreatic acinar tissue. The hypothesis that the impaired glucose-induced insulin secretion during starvation partly is caused by an increased content of biogenic amines in the pancreatic islets was not supported by our experiments which showed an unchanged islet content of these amines after 48 h starvation. (author)

  6. Analysis of changes in the expression pattern of claudins using salivary acinar cells in primary culture.

    Science.gov (United States)

    Fujita-Yoshigaki, Junko

    2011-01-01

    Primary saliva is produced from blood plasma in the acini of salivary glands and is modified by ion adsorption and secretion as the saliva passes through the ducts. In rodents, acinar cells of salivary glands express claudin-3 but not claudin-4, whereas duct cells express both claudins-3 and -4. The distinct claudin expression patterns may reflect differences in the permeability of tight junctions between acinar and duct cells. To analyze the role of claudins in salivary glands, we established a system for the primary culture of parotid acinar cells, where the expression patterns of claudins are remarkably changed. Real-time RT-PCR and immunoblot analyses reveal that the expression levels of claudins-4 and -6 increased, whereas claudins-3 and -10 decreased. We found that the signal to induce those changes is triggered during cell isolation and is mediated by Src and p38 MAP kinase. Here, we introduce the methods used to determine the signal pathway that induces the change in claudin expression.

  7. Acinus-on-a-chip: a microfluidic platform for pulmonary acinar flows

    Science.gov (United States)

    Fishler, Rami; Mulligan, Molly; Sznitman, Josue; Sznitman Biofluids Team

    2013-11-01

    Convective respiratory flows in the pulmonary acinus and their influence on the fate of inhaled particles are typically studied using computational fluid dynamics (CFD) or scaled-up experimental models. However, current experiments generally capture only flow dynamics, without inhaled particle dynamics, due to difficulties in simultaneously matching flow and particle dynamics. In an effort to overcome these limitations, we have designed a novel microfluidic device mimicking acinar flow conditions directly at the physiological scale. The model features an anatomically-inspired acinar geometry with five dichotomously branching airway generations lined with periodically expanding and contracting alveoli. Using micro-particle image velocimetry (PIV), we reveal experimentally a gradual transition of alveolar flow patterns along the acinar tree from recirculating to radial streamlines, in support of previous predictions from CFD simulations. We demonstrate the applicability of the device for studying the mechanisms of particle deposition in the pulmonary acinus by mapping deposition sites of airborne fluorescent micro-particles (0.1-1 μm) and visualizing trajectories of airborne incense particles inside the system.

  8. Pancreatic Pseudocyst Pleural Fistula in Gallstone Pancreatitis

    Directory of Open Access Journals (Sweden)

    Sala Abdalla

    2016-01-01

    Full Text Available Extra-abdominal complications of pancreatitis such as pancreaticopleural fistulae are rare. A pancreaticopleural fistula occurs when inflammation of the pancreas and pancreatic ductal disruption lead to leakage of secretions through a fistulous tract into the thorax. The underlying aetiology in the majority of cases is alcohol-induced chronic pancreatitis. The diagnosis is often delayed given that the majority of patients present with pulmonary symptoms and frequently have large, persistent pleural effusions. The diagnosis is confirmed through imaging and the detection of significantly elevated amylase levels in the pleural exudate. Treatment options include somatostatin analogues, thoracocentesis, endoscopic retrograde cholangiopancreatography (ERCP with pancreatic duct stenting, and surgery. The authors present a case of pancreatic pseudocyst pleural fistula in a woman with gallstone pancreatitis presenting with recurrent pneumonias and bilateral pleural effusions.

  9. Relaxin prevents the development of severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Laura Iris Cosen-Binker; Marcelo Gustavo Binker; Rodica Cosen; Gustavo Negri; Osvaldo Tiscornia

    2006-01-01

    AIM: To investigate the severity of acute pancreatitis (AP) is associated to the intensity of leukocyte activation,inflammatory up-regulation and microcirculatory disruption associated to ischemia-reperfusion injury.Microvascular integrity and inhibition of pro-inflammatory mediators are key-factors in the evolution of AP. Relaxin is an insulin-like hormone that has been attributed vasorelaxant properties via the nitric oxide pathway while behaving as a glucocorticoid receptor agonist.METHODS: AP was induced by the bilio-pancreatic duct-outlet-exclusion closed-duodenal-loops model.Treatment with relaxin was done at different timepoints. Nitric oxide synthase inhibition by L-NAME and glucocorticoid receptor (GR) blockage by mifepristone was considered. AP severity was assessed by biochemical and histopathological analyses.RESULTS: Treatment with relaxin reduced serum amylase, lipase, C-reactive protein, IL-6, IL-10, hsp72,LDH and 8-isoprostane as well as pancreatic and lung myeloperoxidase. Acinar and fat necrosis, hemorrhage and neutrophil infiltrate were also decreased. ATP depletion and ADP/ATP ratio were reduced while caspases 2-3-8 and 9 activities were increased. L-NAME and mifepristone decreased the efficiency of relaxin.CONCLUSION: Relaxin resulted beneficial in the treatment of AP combining the properties of a GR agonist while preserving the microcirculation and favoring apoptosis over necrosis.

  10. Autoimmune pancreatitis can develop into chronic pancreatitis

    OpenAIRE

    Maruyama, Masahiro; Watanabe, Takayuki; Kanai, Keita; Oguchi, Takaya; Asano, Jumpei; Ito, Tetsuya; Ozaki, Yayoi; Muraki, Takashi; Hamano, Hideaki; ARAKURA, Norikazu; Kawa, Shigeyuki

    2014-01-01

    Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into o...

  11. Pancreatitis-imaging approach

    Institute of Scientific and Technical Information of China (English)

    Kiran; K; Busireddy; Mamdoh; AlObaidy; Miguel; Ramalho; Janaka; Kalubowila; Liu; Baodong; Ilaria; Santagostino; Richard; C; Semelka

    2014-01-01

    Pancreatitis is defined as the inflammation of the pancreas and considered the most common pancreatic disease in children and adults. Imaging plays a significant role in the diagnosis, severity assessment, recognition of complications and guiding therapeutic interventions. In the setting of pancreatitis, wider availability and good image quality make multi-detector contrastenhanced computed tomography(MD-CECT) the most used imaging technique. However, magnetic resonance imaging(MRI) offers diagnostic capabilities similar to those of CT, with additional intrinsic advantages including lack of ionizing radiation and exquisite soft tissue characterization. This article reviews the proposed definitions of revised Atlanta classification for acute pancreatitis, illustrates a wide range of morphologic pancreatic parenchymal and associated peripancreatic changes for different types of acute pancreatitis. It also describes the spectrum of early and late chronic pancreatitis imaging findings and illustrates some of the less common types of chronic pancreatitis, with special emphasis on the role of CT and MRI.

  12. Acute Pancreatitis in Children

    Science.gov (United States)

    ... a feeding tube or an IV to prevent malnutrition and improve healing. Does my child have to ... intestines. Can my child die from acute pancreatitis? Death from acute pancreatitis is quite rare in children– ...

  13. Pancreatitis - series (image)

    Science.gov (United States)

    ... common bile duct and block the flow of pancreatic enzymes out of the pancreas into the intestine. Pancreatitis ... three to five days, to prevent secretion of enzymes by the pancreas. He will also receive pain medication to control ...

  14. Surgery for pancreatic cancer

    Science.gov (United States)

    ... medlineplus.gov/ency/article/007649.htm Surgery for pancreatic cancer To use the sharing features on this page, ... surgery are used in the surgical treatment of pancreatic cancer. Whipple procedure: This is the most common surgery ...

  15. Pancreatic Cancer Stage 3

    Science.gov (United States)

    ... 3 Description: Stage III pancreatic cancer; drawing shows cancer in the pancreas, common hepatic artery, and portal vein. Also shown ... and superior mesenteric artery. Stage III pancreatic cancer. Cancer ... near the pancreas. These include the superior mesenteric artery, celiac axis, ...

  16. Autoimmune pancreatitis: A review

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Autoimmune pancreatitis has emerged over the last 40 years from a proposed concept to a well established and recognized entity. As an efficient mimicker of pancreatic carcinoma, its early and appropriate recognition are crucial. With mounting understanding of its pathogenesis and natural history, significant advances have been made in the diagnosis of autoimmune pancreatitis. The characteristic laboratory features and imaging seen in autoimmune pancreatitis are reviewed along with some of the proposed diagnostic criteria and treatment algorithms.

  17. Diabetes and pancreatic cancer

    OpenAIRE

    MUNIRAJ, T.; Chari, S.T.

    2012-01-01

    The relationship between diabetes and pancreatic cancer is complex. Diabetes or impaired glucose tolerance is present in more than 2/3rd of pancreatic cancer patients. Epidemiological studies have consistently shown a modest increase in the risk of pancreatic cancer in type 2 diabetes, with an inverse relationship to duration of disease. Additionally, recent studies suggest that anti-diabetic medications may modulate the risk of pancreatic cancer in type 2 diabetes. Subjects >50 years of age ...

  18. Stages of Pancreatic Cancer

    Science.gov (United States)

    ... affect prognosis (chance of recovery) and treatment options. Pancreatic cancer is a disease in which malignant (cancer) cells form in the ... the cancer cells in the liver are actually pancreatic cancer cells. The disease is metastatic pancreatic cancer, not liver cancer. The ...

  19. Biomarkers for pancreatic carcinogenesis

    NARCIS (Netherlands)

    Hustinx, S.R.

    2007-01-01

    Pancreatic cancer is a devastating disease. Most pancreatic cancers (approximately 85%) are diagnosed at a late, incurable stage. The poor prognosis and late presentation of pancreatic cancer patients underscore the importance of early detection, which is the sine qua non for the fight against pancr

  20. Pancreatic Cancer Risk Factors

    Science.gov (United States)

    ... factors can affect a person’s chance of getting cancer of the pancreas. Most of these are risk factors for exocrine ... Chronic pancreatitis, a long-term inflammation of the pancreas, is linked with an increased risk of pancreatic cancer (especially in smokers), but most people with pancreatitis ...

  1. A Novel Ras Inhibitor (MDC-1016 Reduces Human Pancreatic Tumor Growth in Mice

    Directory of Open Access Journals (Sweden)

    Gerardo G Mackenzie

    2013-10-01

    Full Text Available Pancreatic cancer has one of the poorest prognoses among all cancers partly because of its persistent resistance to chemotherapy. The currently limited treatment options for pancreatic cancer underscore the need for more efficient agents. Because activating Kras mutations initiate and maintain pancreatic cancer, inhibition of this pathway should have a major therapeutic impact. We synthesized phospho-farnesylthiosalicylic acid (PFTS; MDC-1016 and evaluated its efficacy, safety, and metabolism in preclinical models of pancreatic cancer. PFTS inhibited the growth of human pancreatic cancer cells in culture in a concentration- and time-dependent manner. In an MIA PaCa-2 xenograft mouse model, PFTS at a dose of 50 and 100 mg/kg significantly reduced tumor growth by 62% and 65% (P < .05 vs vehicle control. Furthermore, PFTS prevented pancreatitis-accelerated acinar-to-ductal metaplasia in mice with activated Kras. PFTS appeared to be safe, with the animals showing no signs of toxicity during treatment. Following oral administration, PFTS was rapidly absorbed, metabolized to FTS and FTS glucuronide, and distributed through the blood to body organs. Mechanistically, PFTS inhibited Ras-GTP, the active form of Ras, both in vitro and in vivo, leading to the inhibition of downstream effector pathways c-RAF/mitogen-activated protein-extracellular signal-regulated kinase (ERK kinase (MEK/ERK1/2 kinase and phosphatidylinositol 3-kinase/AKT. In addition, PFTS proved to be a strong combination partner with phospho-valproic acid, a novel signal transducer and activator of transcription 3 (STAT3 inhibitor, displaying synergy in the inhibition of pancreatic cancer growth. In conclusion, PFTS, a direct Ras inhibitor, is an efficacious agent for the treatment of pancreatic cancer in preclinical models, deserving further evaluation.

  2. Peculiarities of death and regeneration of pancreas cells at early stages of alcoholic chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    N. Y. Oshmyanska

    2014-10-01

    Full Text Available The study has been conducted on 39 white laboratory male rats which formed 5 groups: experimental occlusal pancreatitis caused by ligation of the main pancreatic duct (n = 6, experimental alcoholic pancreatitis caused by oral intake of alcohol (n = 6, against the background of an excess (n = 6 or deficiency (n = 6 of nitric oxide, as well as a control group (n = 15. This study provides the detailed description of the processes of death and regeneration in the islets of Langerhans, typical for early stages of the disease. The expression of the proliferation markers (PCNA and Neurogenin-3 has been analyzed using histological and immunohistochemical methods along with the changes of morphological structure, that led to initiation of the alcoholic chronic pancreatitis against the background of imbalance in NO-ergic regulatory system caused by an excess or deficiency of nitric oxide. It has been found that ligation of the pancreatic duct in the experiment reconstructedthe circumstances of chronic pancreatitis in rats and caused the activation of fibrosis and regeneration of endocrine and exocrine tissue. Compared with occlusion, the effects of ethanol on the pancreas also manifested in the activation of fibrogenesis, but the structural changes were negligible and could unlikely lead to advanced fibrosis and chronic pancreatitis in the future. On the other side, an imbalance of NO-system in alcoholic rats leads to disruption of the zymogens secretion in the acinar cells and dilatation of the capillary network in islets. Uneven distribution of zymogen granules may lead to their intracellular activation as evidenced by the deformation of acini and focal apoptosis without inflammatory response. In this case, violation of the key adaptive responses in the pancreas makes it more vulnerable to the effects of ethanol, its metabolites, and other environmental factors, and may increase the probability of chronic pancreatitis development. At the same time

  3. Caerulin-induced pancreatitis in rats: Histological and genetic expression changes from acute phase to recuperation

    Institute of Scientific and Technical Information of China (English)

    Javier Maga(n)a-Gómez; Guillermo López-Cervantes; Ana María Calderón de la Barca

    2006-01-01

    AIM: To study the histological and pancreatitis-associated protein mRNA accumulation changes of pancreas from acute phase of caerulin-induced pancreatitis to recuperation in rats.METHODS: Acute pancreatitis was induced by caerulein in male Wistar rats and followed up for 90 d by histologicai and mRNA analyses of pancreas. Pancreases were dissected at 0, 9, 24 h and 3, 5, 15, 30, 60, 90 d post-induction. Edema (E), polymorphonuclear neutrophil (PMN) infiltration, cytoplasmic vacuolization (V), zymogen granule depletion (ZD) and acinar disorganization (AD) were microscopically evaluated. Accumulation of pancreatitisassociated protein (PAP) and L13A mRNAs were quantifled by real-time PCR.RESULTS: The main histological changes appeared at 9 h post-induction for PMN infiltration and cytoplasmic V, while at 24 h and 3 d for E and ZD, respectively. All the parameters were recovered after 5 d, except for ZD which delayed more than 30 d. The main AD was observed after 15 d and values returned to normal after 30 d. Similarly to histological changes, accumulation of the PAP mRNA was increased at 9 h with the highest accumulation at 24 h and differences disappeared after 5 d.CONCLUSION: From the acute phase to recuperation of pancreatitis, regeneration and re-differentiation of pancreas occur and PAP expression is exclusively an acute response of pancreatitis.

  4. A simple taurocholate-induced model of severe acute pancreatitis in rats

    Institute of Scientific and Technical Information of China (English)

    Zhong-Hui Liu; Jun-Sheng Peng; Chu-Jun Li; Zu-Li Yang; Jun Xiang; Hu Song; Xiao-Bing Wu; Jun-Rong Chen; De-Chang Diao

    2009-01-01

    AIM: To investigate gut barrier damage and intestinal bacteria translocation in severe acute pancreatitis (SAP),a simple rat model of SAP was induced and studied.METHODS: Pancreatitis was induced by uniformly distributed injection of 3.8% Na taurocholate (1 mL/kg) beneath the pancreatic capsule. Rats in the control group were injected with normal saline in the identical location.RESULTS: Serum amylase, plasma endotoxin, intestinal permeability, and pancreatitis pathology scores were all markedly higher in the pancreatitis group than in the control group ( P < 0.01). The bacterial infection rate was significantly higher in the SAP group than in the control group ( P < 0.01), observed in parallel by both bacterial culture and real-time polymerase chain reaction. Acute damage of the pancreas was observed histologically in SAP rats, showing interstitial edema, leukocyte infiltration, acinar cell necrosis and hemorrhage. The microstructure of the intestinal mucosa of SAP rats appeared to be destroyed with loose, shortened microvilli and rupture of the intercellular junction, as shown by electron microscopy.CONCLUSION: Significant gut barrier damage and intestinal bacterial translocation were definitely observed with few potential study confounders in this SAP rat model, suggesting that it may be an appropriate animal model for study of gut barrier damage and bacterial translocation in SAP.

  5. Role of Parathyroid Hormone-Related Protein Signaling in Chronic Pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Falzon, Miriam, E-mail: mfalzon@utmb.edu; Bhatia, Vandanajay [Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555 (United States)

    2015-06-18

    Chronic pancreatitis (CP), a progressive inflammatory disease where acini are destroyed and replaced by fibrous tissue, increases the risk for pancreatic cancer. Risk factors include alcohol, smoking, and obesity. The effects of these risk factors are exacerbated in patients with mutations in genes that predispose to CP. The different environmental and genetic factors produce the same clinical phenotype; once CP develops, disease course is the same regardless of etiology. Critical questions still need to be answered to understand what modifies predisposition to develop CP in persons exposed to risk factors. We postulate that risk factors modulate endogenous pathways, with parathyroid hormone-related protein (PTHrP) signaling being one such pathway. In support, PTHrP levels are elevated in mice treated with alcohol, and in mouse models of cerulein- and pancreatic duct ligation-induced CP. Disrupting the Pthrp gene in acinar cells exerts protective effects (decreased edema, histological damage, amylase and cytokine release, and fibrosis) in these CP models. PTHrP levels are elevated in human CP. Currently, CP care lacks specific pharmacological interventions. Targeting PTHrP signaling may present a novel therapeutic strategy that inhibits pancreatic inflammation and fibrosis, especially since the risk of developing pancreatic cancer is strongly associated with duration of chronic inflammation.

  6. Recurrent ectopic pancreatitis of the jejunum and mesentery over a 30-year period

    Institute of Scientific and Technical Information of China (English)

    John CT Wong; Charlotte Robinson; Edward C Jones; Alison Harris; Charles Zwirewich; Robert Wakefield; Richard K Simons; Eric M Yoshida

    2011-01-01

    BACKGROUND: Ectopic pancreas is defined as pancreatic tissue found outside its usual anatomical position, with no ductal or vascular communication with the native pancreas. We describe a case of ectopic pancreas of the small bowel and mesentery causing recurrent episodes of pancreatitis, initially suspected on computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP), and confirmed on histological review of the resection. METHODS: A 67-year-old woman presented with clinical symptoms and biochemical evidence of pancreatitis. She had similar episodes over the past 30 years with unrevealing investi-gations, and was concluded to have idiopathic pancreatitis. She underwent CT and MRCP, with findings suggestive of ectopic pancreas, a diagnosis confirmed on histology of the resection. RESULTS: MRCP identified a mass in the proximal small bowel mesentery isointense to the native pancreas, with a small duct draining into a proximal jejunal loop. The resected specimen consisted of normal parenchyma with lobulated acinar tissue with scattered islets of Langerhans, an occasional ductular structure, and admixed areas of adipose tissue. The patient remained asymptomatic with normal biochemistry six months post-operatively. CONCLUSION: In an individual with abdominal pain, elevated serum amylase/lipase, but imaging findings of a normal native pancreas, ectopic pancreatitis should be considered, and can be evaluated by CT and MRCP.

  7. Phospholipase D mediated transphosphatidylation as a possible new pathway of ethanol metabolism in isolated rat pancreatic acini

    International Nuclear Information System (INIS)

    Activation of pancreatic phospholipase D (PLD) has been previously observed in response to caerulein (Cae), phorbol myristate acetate and growth factors. Although PLD involvement has been postulated in pancreatic cell proliferation and differentiation, the physiological role of this enzyme in pancreatic cells still remains unclear. In the presence of ethanol, PLD catalysed transphosphatidylation reaction, forming phosphatidylethanol (PEt). This study was thus undertaken to determine the involvement of PLD in ethanol metabolism in isolated pancreatic acini and to show the potential physiological consequences of transphosphatidylation. Dispersed pancreatic acini prelabelled with 3H myristic acid were incubated with 500 pM Cae in the presence or absence of different concentrations of ethanol, and labelled phosphatidylethanol (3H PEt) production or phosphatidic acid (3H PA) accumulation were measured. The production of PEt after Cae stimulation in pancreatic acini was significant from 0.5% up to 4% of ethanol in the medium and was not dependent on increasing concentration of ethanol. Prolonged up to 2 h stimulation with Cae in the presence of 1% ethanol did not increase PEt production which was almost stable since 5 min of stimulation. In the presence of different concentrations of ethanol (1-4%), the significant inhibition of PA accumulation was obtained after Cae stimulation, similar to inhibition with a specific PLD inhibitor-wortmannin. These data indicate that Cae activated PLD in the presence of ethanol caused PEt production in pancreatic acini. During formation of PEt in pancreatic acinar cells significant and parallel inhibition of PA accumulation was observed. This indicates the relation of PLD activation in isolated pancreatic acini to ethanol metabolism. Ethanol can act as an inhibitor of PLD activity. Since PA, a product of PLD, is known as a second messenger probably involved in cell proliferation and differentiation, this may suggest a potentially new

  8. Enzymatic Debridement in Necrotizing Pancreatitis

    OpenAIRE

    Cakir, Murat; Tekin, Ahmet; Kucukkartallar, Tevfik; Vatansev, Husamettin; Kartal, Adil

    2015-01-01

    Multiple organ failure and pancreatic necrosis are the factors that determine prognosis in acute pancreatitis attacks. We investigated the effects of collagenase on the debridement of experimental pancreatic necrosis. The study covered 4 groups; each group had 10 rats. Group I was the necrotizing pancreatitis group. Group II was the collagenase group with pancreatic loge by isotonic irrigation following necrotizing pancreatitis. Group III was the collagenase group with pancreatic loge followi...

  9. Features of glycoproteins distribution in the pancreatic structures of newborn rats after prenatal antigenic influence

    Directory of Open Access Journals (Sweden)

    Grinivetska N.V.

    2014-03-01

    Full Text Available Background. Abnormalities of digestion and absorption are the most common syndromes associated with the digestive system diseases in children. Pancreatic enzyme failure leads to violation of different metabolic processes, especially in neonates. Exocrine pancreas is sensitive to a variety of factors, including virus. It emphasizes the importance of investigation of pancreatic secretory activity in children who was born from mothers exposed to viral infection during pregnancy. Objective. The purpose is to determine the features of glycoproteins distribution in the pancreatic structures of newborn rats after prenatal antigenic influence. Methods. Animals were divided into four groups: the 1st – intact, the 2nd – intrafetal injection of the antigen, the 3rd – animals administered with antigen into the amniotic fluid, and the 4th group – control (intrafetal injection of a normal salt solution. As antigen we used Vaxigrip vaccine. Results. It was revealed that on the14th day after birth antigen-exposed animals were characterized by the increase of glycoproteins (++ in a connective tissue capsule of pancreas and decreased content of glycoproteins in the cytoplasm of acinar cells and ducts comparing with the intact group (++/+. Taken together this data evidence the reduction of the synthetic activity of acinar cells after intrafetal administration of the antigen. This may cause a predisposition for the development of dyspepsia and food allergy. Further work is planned to investigate the dynamics of glycosaminoglycans redistribution in different parts of pancreas after prenatal antigenic administrations. Citation: Grinivetska NV. [Features of glycoproteins distribution in the pancreatic structures of newborn rats after prenatal antigenic influence]. Morphologia. 2014;8(1:30-4. Ukrainian.

  10. Cannabinoid receptors in submandibular acinar cells: functional coupling between saliva fluid and electrolytes secretion and Ca2+ signalling.

    Science.gov (United States)

    Kopach, Olga; Vats, Juliana; Netsyk, Olga; Voitenko, Nana; Irving, Andrew; Fedirko, Nataliya

    2012-04-15

    Cannabinoid receptors (CBRs) belong to the G protein-coupled receptor superfamily, and activation of CBRs in salivary cells inhibits agonist-stimulated salivation and modifies saliva content. However, the role of different CBR subtypes in acinar cell physiology and in intracellular signalling remains unclear. Here, we uncover functional CB(1)Rs and CB(2)Rs in acinar cells of rat submandibular gland and their essential role in saliva secretion. Pharmacological activation of CB(1)Rs and CB(2)Rs in the submandibular gland suppressed saliva outflow and modified saliva content produced by the submandibular gland in vivo. Using Na(+)-selective microelectrodes to record secretory Na(+) responses in the lumen of acini, we observed a reduction in Na(+) transport following the activation of CBRs, which was counteracted by the selective CB(1)R antagonist AM251. In addition, activation of CB(1)Rs or CB Rs caused inhibition of Na(+)-K(+) 2 -ATPase activity in microsomes derived from the gland tissue as well as in isolated acinar cells. Using a Ca(2+) imaging technique, we showed that activation of CB(1)Rs and CB(2)Rs alters [Ca(2+)](cyt) signalling in acinar cells by distinct pathways, involving Ca(2+) release from the endoplasmic reticulum (ER) and store-operated Ca(2+) entry (SOCE), respectively. Our data demonstrate the expression of CB(1)Rs and CB(2)Rs in acinar cells, and their involvement in the regulation of salivary gland functioning.

  11. Pancreatitis in children.

    Science.gov (United States)

    Winchester, M

    1992-12-01

    The pathophysiology of pancreatic autodigestion is poorly understood. Pancreatitis affects all age groups, and the diagnosis is sometimes missed when serum amylase and lipase activities are not measured in the child with abdominal pain. Acute pancreatitis in children has become a more commonly seen condition and the causes have varied. Laboratory and radiological studies play an important role in determining the diagnosis and prognosis. Family history is important in the diagnosis of idiopathic hereditary pancreatitis. Most acute episodes resolve with supportive care, but the mortality in acute pancreatitis is currently about 15% (Hadorn et al., 1980). Endoscopic retrograde cholangiopancreatography or an endoscopic retrograde pancreatogram may be necessary to investigate relapses of pancreatitis. Chronic pancreatitis can be a life-threatening condition requiring lifetime medical management.

  12. Pancreatitis. An update

    International Nuclear Information System (INIS)

    Acute and chronic pancreatitis are becoming increasingly more severe diseases in the western world with far-reaching consequences for the individual patient as well as the socioeconomic situation. This article gives an overview of the contribution of radiological imaging to the diagnostics and therapy of both forms of the disease. Acute pancreatitis can be subdivided into severe (20 %) and mild manifestations. The diagnostics should be performed with computed tomography (CT) or magnetic resonance imaging (MRI) for assessing necrosis or potential infections only in severe forms of pancreatitis. In chronic pancreatitis transabdominal ultrasound should initially be adequate for assessment of the pancreas. For the differential diagnosis between pancreatic carcinoma and chronic pancreatitis, MRI with magnetic resonance cholangiopancreatography (MRCP) followed by an endoscopic ultrasound-guided fine needle aspiration is the method of choice. For the primary diagnosis for acute and chronic pancreatitis ultrasound examination is the modality of first choice followed by radiological CT and MRI with MRCP examinations. (orig.)

  13. Extracellular matrix composition significantly influences pancreatic stellate cell gene expression pattern: role of transgelin in PSC function.

    Science.gov (United States)

    Apte, Minoti V; Yang, Lu; Phillips, Phoebe A; Xu, Zhihong; Kaplan, Warren; Cowley, Mark; Pirola, Romano C; Wilson, Jeremy S

    2013-09-15

    Activated pancreatic stellate cells (PSCs) are responsible for the fibrotic matrix of chronic pancreatitis and pancreatic cancer. In vitro protocols examining PSC biology have usually involved PSCs cultured on plastic, a nonphysiological surface. However, PSCs cultured on physiological matrices, e.g., Matrigel (normal basement membrane) and collagen (fibrotic pancreas), may have distinctly different behaviors compared with cells cultured on plastic. Therefore, we aimed to 1) compare PSC gene expression after culture on plastic, Matrigel, and collagen I; 2) validate the gene array data for transgelin, the most highly dysregulated gene in PSCs grown on activating vs. nonactivating matrices, at mRNA and protein levels; 3) examine the role of transgelin in PSC function; and 4) assess transgelin expression in human chronic pancreatitis sections. Culture of PSCs on different matrices significantly affected their gene expression pattern. 146, 619, and 432 genes, respectively, were differentially expressed (P PSC proliferation and also reduced platelet-derived growth factor-induced PSC migration. Notably, transgelin was highly expressed in chronic pancreatitis in stromal areas and periacinar spaces but was absent in acinar cells. These findings suggest that transgelin is a potentially useful target protein to modulate PSC function so as to ameliorate pancreatic fibrosis.

  14. Role of bone marrow-derived mesenchymal stem cells in a rat model of severe acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Xiao-Huang Tu; Jing-Xiang Song; Xiao-Jun Xue; Xian-Wei Guo; Yun-Xia Ma; Zhi-Yao Chen; Zhong-Dong Zou; Lie Wang

    2012-01-01

    AIM:To investigate the role and potential mechanisms of bone marrow mesenchymal stem cells (MSCs) in severe acute peritonitis (SAP).METHODS:Pancreatic acinar cells from Sprague Dawley rats were randomly divided into three groups:nonsodium deoxycholate (SDOC) group (non-SODC group),SDOC group,and a MSCs intervention group (i.e.,a co-culture system of MSCs and pancreatic acinar cells + SDOC).The cell survival rate,the concentration of malonaldehyde (MDA),the density of superoxide dismutase (SOD),serum amylase (AMS) secretion rate and lactate dehydrogenase (LDH) leakage rate were detected at various time points.In a separate study,Sprague Dawley rats were randomly divided into either an SAP group or an SAP + MSCs group.Serum AMS,MDA and SOD,interleukin (IL)-6,IL-10,and tumor necrosis factor (TNF)-α levels,intestinal mucosa injury scores and proliferating cells of small intestinal mucosa were measured at various time points after injecting either MSCs or saline into rats.In both studies,the protective effect of MSCs was evaluated.RESULTS:In vitro,The cell survival rate of pancreatic acinar cells and the density of SOD were significantly reduced,and the concentration of MDA,AMS secretion rate and LDH leakage rate were significantly increased in the SDOC group compared with the MSCs intervention group and the Non-SDOC group at each time point.In vivo,Serum AMS,IL-6,TNF-α and MAD level in the SAP + MSCs group were lower than the SAP group;however serum IL-10 level was higher than the SAP group.Serum SOD level was higher than the SAP group at each time point,whereas a significant betweengroup difference in SOD level was only noted after 24 h.Intestinal mucosa injury scores was significantly reduced and the proliferating cells of small intestinal mucosa became obvious after injecting MSCs.CONCLUSION:MSCs can effectively relieve injury to pancreatic acinar cells and small intestinal epithelium,promote the proliferation of enteric epithelium and repair of the mucosa

  15. Inhibition of proliferation by PERK regulates mammary acinar morphogenesis and tumor formation.

    Directory of Open Access Journals (Sweden)

    Sharon J Sequeira

    Full Text Available Endoplasmic reticulum (ER stress signaling can be mediated by the ER kinase PERK, which phosphorylates its substrate eIF2alpha. This in turn, results in translational repression and the activation of downstream programs that can limit cell growth through cell cycle arrest and/or apoptosis. These responses can also be initiated by perturbations in cell adhesion. Thus, we hypothesized that adhesion-dependent regulation of PERK signaling might determine cell fate. We tested this hypothesis in a model of mammary acini development, a morphogenetic process regulated in part by adhesion signaling. Here we report a novel role for PERK in limiting MCF10A mammary epithelial cell proliferation during acinar morphogenesis in 3D Matrigel culture as well as in preventing mammary tumor formation in vivo. We show that loss of adhesion to a suitable substratum induces PERK-dependent phosphorylation of eIF2alpha and selective upregulation of ATF4 and GADD153. Further, inhibition of endogenous PERK signaling during acinar morphogenesis, using two dominant-negative PERK mutants (PERK-DeltaC or PERK-K618A, does not affect apoptosis but results instead in hyper-proliferative and enlarged lumen-filled acini, devoid of proper architecture. This phenotype correlated with an adhesion-dependent increase in translation initiation, Ki67 staining and upregulation of Laminin-5, ErbB1 and ErbB2 expression. More importantly, the MCF10A cells expressing PERKDeltaC, but not a vector control, were tumorigenic in vivo upon orthotopic implantation in denuded mouse mammary fat pads. Our results reveal that the PERK pathway is responsive to adhesion-regulated signals and that it is essential for proper acinar morphogenesis and in preventing mammary tumor formation. The possibility that deficiencies in PERK signaling could lead to hyperproliferation of the mammary epithelium and increase the likelihood of tumor formation, is of significance to the understanding of breast cancer.

  16. Protective Effects of Hydrogen Gas on Experimental Acute Pancreatitis.

    Directory of Open Access Journals (Sweden)

    Hao-Xin Zhou

    Full Text Available Acute pancreatitis (AP is an inflammatory disease mediated by damage to acinar cells and pancreatic inflammation. In patients with AP, subsequent systemic inflammatory responses and multiple organs dysfunction commonly occur. Interactions between cytokines and oxidative stress greatly contribute to the amplification of uncontrolled inflammatory responses. Molecular hydrogen (H2 is a potent free radical scavenger that not only ameliorates oxidative stress but also lowers cytokine levels. The aim of the present study was to investigate the protective effects of H2 gas on AP both in vitro and in vivo. For the in vitro assessment, AR42J cells were treated with cerulein and then incubated in H2-rich or normal medium for 24 h, and for the in vivo experiment, AP was induced through a retrograde infusion of 5% sodium taurocholate into the pancreatobiliary duct (0.1 mL/100 g body weight. Wistar rats were treated with inhaled air or 2% H2 gas and sacrificed 12 h following the induction of pancreatitis. Specimens were collected and processed to measure the amylase and lipase activity levels; the myeloperoxidase activity and production levels; the cytokine mRNA expression levels; the 8-hydroxydeoxyguanosine, malondialdehyde, and glutathione levels; and the cell survival rate. Histological examinations and immunohistochemical analyses were then conducted. The results revealed significant reductions in inflammation and oxidative stress both in vitro and in vivo. Furthermore, the beneficial effects of H2 gas were associated with reductions in AR42J cell and pancreatic tissue damage. In conclusion, our results suggest that H2 gas is capable of ameliorating damage to the pancreas and AR42J cells and that H2 exerts protective effects both in vitro and in vivo on subjects with AP. Thus, the results obtained indicate that this gas may represent a novel therapy agent in the management of AP.

  17. Therapy of pancreatic cancer

    International Nuclear Information System (INIS)

    Pancreatic cancer remains one of the most difficult diseases to cure. Japan pancreas society guidelines for management of pancreatic cancer indicate therapeutic algorithm according to the clinical stage. For locally limited pancreatic cancer (cStage I, II, III in Japanese classification system), surgical resection is recommended, however prognosis is still poor. Major randomized controlled trials of resected pancreatic cancer indicates that adjuvant chemotherapy is superior to observation and gemcitabine is superior to 5-fluorouracil (FU). For locally advanced resectable pancreatic cancer (cStage IVa in Japanese classification system (JCS)), we perform neoadjuvant chemoradiotherapy. Phase I study established a recommended dose of 800 mg gemcitabine and radiation dose of 36 Gy. For locally advanced nonresectable pancreatic cancer (cStage IVa in JCS), chemoradiotherapy followed by chemotherapy is recommended. Although pancreatic cancer is chemotherapy resistant tumor, systemic chemotherapy is recommended for metastatic pancreatic cancer (cStage IVb in JCS). Single-agent gemcitabine is the standard first line agent for the treatment of advanced pancreatic cancer. Meta-analysis of chemotherapy showed possibility of survival benefit of gemcitabine combination chemotherapy over gemcitabine alone. We hope gemcitabine combination chemotherapy or molecular targeted therapy will improve prognosis of pancreatic cancer in the future. (author)

  18. High fat diet and GLP-1 drugs induce pancreatic injury in mice

    Energy Technology Data Exchange (ETDEWEB)

    Rouse, Rodney, E-mail: rodney.rouse@fda.hhs.gov; Xu, Lin; Stewart, Sharron; Zhang, Jun

    2014-04-15

    Glucagon Like Peptide-1 (GLP-1) drugs are currently used to treat type-2 diabetes. Safety concerns for increased risk of pancreatitis and pancreatic ductal metaplasia have accompanied these drugs. High fat diet (HFD) is a type-2 diabetes risk factor that may affect the response to GLP-1 drug treatment. The objective of the present study was to investigate the effects of diet and GLP-1 based drugs on the exocrine pancreas in mice. Experiments were designed in a mouse model of insulin resistance created by feeding a HFD or standard diet (STD) for 6 weeks. The GLP-1 drugs, sitagliptin (SIT) and exenatide (EXE) were administered once daily for additional 6 weeks in both mice fed HFD or STD. The results showed that body weight, blood glucose levels, and serum levels of pro-inflammatory cytokines (TNFα, IL-1β, and KC) were significantly greater in HFD mice than in STD mice regardless of GLP-1 drug treatment. The semi-quantitative grading showed that pancreatic changes were significantly greater in EXE and SIT-treated mice compared to control and that HFD exacerbated spontaneous exocrine pancreatic changes seen in saline-treated mice on a standard diet. Exocrine pancreatic changes identified in this study included acinar cell injury (hypertrophy, autophagy, apoptosis, necrosis, and atrophy), vascular injury, interstitial edema and inflammation, fat necrosis, and duct changes. These findings support HFD as a risk factor to increased susceptibility/severity for acute pancreatitis and indicate that GLP-1 drugs cause pancreatic injury that can be exacerbated in a HFD environment.

  19. Age-dependent effects of UCP2 deficiency on experimental acute pancreatitis in mice.

    Directory of Open Access Journals (Sweden)

    Sarah Müller

    Full Text Available Reactive oxygen species (ROS have been implicated in the pathogenesis of acute pancreatitis (AP for many years but experimental evidence is still limited. Uncoupling protein 2 (UCP2-deficient mice are an accepted model of age-related oxidative stress. Here, we have analysed how UCP2 deficiency affects the severity of experimental AP in young and older mice (3 and 12 months old, respectively triggered by up to 7 injections of the secretagogue cerulein (50 μg/kg body weight at hourly intervals. Disease severity was assessed at time points from 3 hours to 7 days based on pancreatic histopathology, serum levels of alpha-amylase, intrapancreatic trypsin activation and levels of myeloperoxidase (MPO in lung and pancreatic tissue. Furthermore, in vitro studies with pancreatic acini were performed. At an age of 3 months, UCP2-/- mice and wild-type (WT C57BL/6 mice were virtually indistinguishable with respect to disease severity. In contrast, 12 months old UCP2-/- mice developed a more severe pancreatic damage than WT mice at late time points after the induction of AP (24 h and 7 days, respectively, suggesting retarded regeneration. Furthermore, a higher peak level of alpha-amylase activity and gradually increased MPO levels in pancreatic and lung tissue were observed in UCP2-/- mice. Interestingly, intrapancreatic trypsin activities (in vivo studies and intraacinar trypsin and elastase activation in response to cerulein treatment (in vitro studies were not enhanced but even diminished in the knockout strain. Finally, UCP2-/- mice displayed a diminished ratio of reduced and oxidized glutathione in serum but no increased ROS levels in pancreatic acini. Together, our data indicate an aggravating effect of UCP2 deficiency on the severity of experimental AP in older but not in young mice. We suggest that increased severity of AP in 12 months old UCP2-/- is caused by an imbalanced inflammatory response but is unrelated to acinar cell functions.

  20. Pancreatic Cancer Stage 2A

    Science.gov (United States)

    ... 2A Description: Stage IIA pancreatic cancer; drawing shows cancer in the pancreas and duodenum. The bile duct and pancreatic duct are also shown. Stage IIA pancreatic cancer. Cancer has spread to nearby tissue and organs ...

  1. Pancreatic Cancer Stage 2B

    Science.gov (United States)

    ... 2B Description: Stage IIB pancreatic cancer; drawing shows cancer in the pancreas and in nearby lymph nodes. Also shown are the bile duct, pancreatic duct, and duodenum. Stage IIB pancreatic cancer. Cancer has spread to nearby lymph nodes and ...

  2. Pancreatic Panniculitis: A rare manifestation of Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Ronak Patel

    2015-05-01

    Full Text Available Context Pancreatic panniculitis is a very rare complication associated with pancreatic disease and perhaps even a presage to pancreatic pathology. Case report We present a case of pancreatic panniculitis in a 61 year old patient who was treated for sudden onset of abdominal pain associated with nausea and vomiting secondary to acute pancreatitis of unknown etiology. He subsequently developed skin lesions consistent with pancreatic panniculitis which gradually improved after resolution of his acute condition and treatment with topical steroid cream. Conclusion We discuss and review the literature along with highlighting for the readers the important clinical and histopathologic features of acute pancreatitis associated pancreatic panniculitis.

  3. Gene expression profiling and endothelin in acute experimental pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Helieh S Oz; Ying Lu; Louis P Vera-Portocarrero; Pei Ge; Ada Silos-Santiago; Karin N Westlund

    2012-01-01

    AIM:To analyze gene expression profiles in an experimental pancreatitis and provide functional reversal of hypersensitivity with candidate gene endothelin-1 antagonists.METHODS:Dibutyltin dichloride (DBTC) is a chemical used as a polyvinyl carbonate stabilizer/catalyzer,biocide in agriculture,antifouling agent in paint and fabric.DBTC induces an acute pancreatitis flare through generation of reactive oxygen species.Lewis-inbred rats received a single i.v.injection with either DBTC or vehicle.Spinal cord and dorsal root ganglia (DRG) were taken at the peak of inflammation and processed for transcriptional profiling with a cDNA microarray biased for rat brain-specific genes.In a second study,groups of animals with DBTC-induced pancreatitis were treated with endothelin (ET) receptor antagonists [ET-A (BQ123) and ET-B BQ788)].Spontaneous pain related mechanical and thermal hypersensitivity were measured.Immunohistochemical analysis was performed using anti-ET-A and ET-B antibodies on sections from pancreatic tissues and DRG of the T10-12 spinal segments.RESULTS:Animals developed acute pancreatic inflammation persisting 7-10 d as confirmed by pathological studies (edema in parenchyma,loss of pancreatic architecture and islets,infiltration of inflammatory cells,neutrophil and mononuclear cells,degeneration,vacuolization and necrosis of acinar cells) and the painrelated behaviors (cutaneous secondary mechanical and thermal hypersensitivity).Gene expression profile was different in the spinal cord from animals with pancreatitis compared to the vehicle control group.Over 260 up-regulated and 60 down-regulated unique genes could be classified into 8 functional gene families:circulatory/acute phase/immunomodulatory; extracellular matrix; structural; channel/receptor/transporter; signaling transduction; transcription/translation-related; antioxidants/chaperones/heat shock; pancreatic and other enzymes.ET-1 was among the 52 candidate genes upregulated greater than 2-fold in

  4. Walled-off pancreatic necrosis

    Institute of Scientific and Technical Information of China (English)

    Michael; Stamatakos; Charikleia; Stefanaki; Konstantinos; Kontzoglou; Spyros; Stergiopoulos; Georgios; Giannopoulos; Michael; Safioleas

    2010-01-01

    Walled-off pancreatic necrosis (WOPN), formerly known as pancreatic abscess is a late complication of acute pancreatitis. It can be lethal, even though it is rare. This critical review provides an overview of the continually expanding knowledge about WOPN, by review of current data from references identified in Medline and PubMed, to September 2009, using key words, such as WOPN, infected pseudocyst, severe pancreatitis, pancreatic abscess, acute necrotizing pancreatitis (ANP), pancreas, inflammation and al...

  5. Hereditary Pancreatic and Hepatobiliary Cancers

    OpenAIRE

    Ashraf Haddad; Kowdley, Gopal C; Timothy M. Pawlik; Cunningham, Steven C.

    2011-01-01

    Hereditary etiologies of pancreatic and hepatobiliary cancers are increasingly recognized. An estimated >10% of pancreatic and increasing number of hepatobiliary cancers are hereditary. The cumulative risk of hereditary pancreatic cancer ranges from measurable but negligible in cystic fibrosis to a sobering 70% in cases of hereditary pancreatitis. Candidates for pancreatic cancer surveillance are those with a risk pancreatic cancer estimated to be >10-fold that of the normal population. Scree...

  6. Restricted diffusion in a model acinar labyrinth by NMR: Theoretical and numerical results

    Science.gov (United States)

    Grebenkov, D. S.; Guillot, G.; Sapoval, B.

    2007-01-01

    A branched geometrical structure of the mammal lungs is known to be crucial for rapid access of oxygen to blood. But an important pulmonary disease like emphysema results in partial destruction of the alveolar tissue and enlargement of the distal airspaces, which may reduce the total oxygen transfer. This effect has been intensively studied during the last decade by MRI of hyperpolarized gases like helium-3. The relation between geometry and signal attenuation remained obscure due to a lack of realistic geometrical model of the acinar morphology. In this paper, we use Monte Carlo simulations of restricted diffusion in a realistic model acinus to compute the signal attenuation in a diffusion-weighted NMR experiment. We demonstrate that this technique should be sensitive to destruction of the branched structure: partial removal of the interalveolar tissue creates loops in the tree-like acinar architecture that enhance diffusive motion and the consequent signal attenuation. The role of the local geometry and related practical applications are discussed.

  7. Transdifferentiation of human amniotic epithelial cells into acinar cells using a double-chamber system.

    Science.gov (United States)

    Huang, Gui-Lin; Zhang, Ni-Ni; Wang, Jun-Sheng; Yao, Li; Zhao, Yu-Jie; Wang, Yu-Ying

    2012-08-01

    This study investigated the transdifferentiation of stem cells from human amnion tissue into functional acinar cells (ACs) using a co-culture system. Human amniotic epithelial cells (hAECs) were isolated from amnion tissue by mechanical mincing and enzymatic digestion. After primary culture, the phenotype of the cells was identified by flow cytometry (FCM) and immunocytochemical staining. hAECs were co-cultured with submandibular gland acinar cells of SD rats using a double-chamber system. The expression of α-amylase was determined by immunocytochemical method and fluorescent real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) after induction for 1 and 2 weeks, respectively. Digestion with trypsin is an effective method for isolating hAECs from amnion tissue. These cells were positive for CD29 and CK19 and weakly positive for CD44 and α-amylase. Within 2 weeks, α-amylase in hAECs increased with induction time. The expression of α-amylase in hAECs was increased 3.38-fold after co-culturing for 1 week. This ratio increased to 6.6-fold, and these cells were positive for mucins, after co-culturing for 2 weeks. hAECs possess the potential to differentiate into ACs in vitro. They might be a stem cell resource for clinical applications of cell replacement therapy in salivary gland dysfunction diseases. PMID:22800093

  8. Acute pancreatitis in pregnancy

    OpenAIRE

    Pitchumoni, Capecomorin S; Yegneswaran, Balaji

    2009-01-01

    Acute pancreatitis (AP) is a rare event in pregnancy, occurring in approximately 3 in 10 000 pregnancies. The spectrum of AP in pregnancy ranges from mild pancreatitis to serious pancreatitis associated with necrosis, abscesses, pseudocysts and multiple organ dysfunction syndromes. Pregnancy related hematological and biochemical alterations influence the interpretation of diagnostic tests and assessment of severity of AP. As in any other disease associated with pregnancy, AP is associated wit...

  9. Smoking and Pancreatic Disease

    OpenAIRE

    2013-01-01

    Smoking is a major risk factor for chronic pancreatitis and pancreatic cancer. However, the mechanisms through which it causes the diseases remain unknown. In the present manuscript we reviewed the latest knowledge gained on the effect of cigarette smoke and smoking compounds on cell signaling pathways mediating both diseases. We also reviewed the effect of smoking on the pancreatic cell microenvironment including inflammatory cells and stellate cells.

  10. Laparoscopy in pancreatic tumors

    OpenAIRE

    Shrikhande S; Barreto S; Shukla P.

    2007-01-01

    Recently, increasing number of manuscripts - original articles and case reports have attempted to provide evidence of the forays of minimal access surgery into pancreatic diseases. Many, based on the lack of Level I evidence, still believe that laparoscopy in pancreatic surgery is experimental. This article attempts to look into data exploring the existing use of minimally invasive surgery in pancreatic disease to answer a vital question - what does the evidence say on the current status of l...

  11. Acute pancreatitis; Pancreatite aigue

    Energy Technology Data Exchange (ETDEWEB)

    Mehdi, M.; Deutsch, J.P.; Arrive, L.; Ayadi, K.; Ladeb, M.F.; Tubiana, J.M. [Centre Hospitalier Universitaire Saint-Antoine, 75 - Paris (France)

    1996-12-31

    The diagnosis of acute pancreatitis is based on clinical examination and basic laboratory tests. The main role of sonography in acute pancreatitis is to evaluate gallstones and small fluid collections. However, sonography is frequently difficult due to intestinal ileus related to pancreatitis. CT is indicated early in the clinical course of acute severe pancreatitis when the diagnosis is uncertain or when complications such as abscess, hemorrhage, or necrosis, are suspected. In addition, CT may be used to assess the prognosis and follow-up of patients. (authors). 20 refs., 12 figs., 4 tabs.

  12. Hepatocyte growth factor signaling in intrapancreatic ductal cells drives pancreatic morphogenesis.

    Directory of Open Access Journals (Sweden)

    Ryan M Anderson

    Full Text Available In a forward genetic screen for regulators of pancreas development in zebrafish, we identified donut(s908 , a mutant which exhibits failed outgrowth of the exocrine pancreas. The s908 mutation leads to a leucine to arginine substitution in the ectodomain of the hepatocyte growth factor (HGF tyrosine kinase receptor, Met. This missense mutation impedes the proteolytic maturation of the receptor, its trafficking to the plasma membrane, and diminishes the phospho-activation of its kinase domain. Interestingly, during pancreatogenesis, met and its hgf ligands are expressed in pancreatic epithelia and mesenchyme, respectively. Although Met signaling elicits mitogenic and migratory responses in varied contexts, normal proliferation rates in donut mutant pancreata together with dysmorphic, mislocalized ductal cells suggest that met primarily functions motogenically in pancreatic tail formation. Treatment with PI3K and STAT3 inhibitors, but not with MAPK inhibitors, phenocopies the donut pancreatic defect, further indicating that Met signals through migratory pathways during pancreas development. Chimera analyses showed that Met-deficient cells were excluded from the duct, but not acinar, compartment in the pancreatic tail. Conversely, wild-type intrapancreatic duct and "tip cells" at the leading edge of the growing pancreas rescued the donut phenotype. Altogether, these results reveal a novel and essential role for HGF signaling in the intrapancreatic ducts during exocrine morphogenesis.

  13. Characterization of pancreatic lesions from MT-tgf alpha, Ela-myc and MT-tgf alpha/Ela-myc single and double transgenic mice.

    Science.gov (United States)

    Liao, Dezhong Joshua; Wang, Yong; Wu, Jiusheng; Adsay, Nazmi Volkan; Grignon, David; Khanani, Fayyaz; Sarkar, Fazlul H

    2006-07-05

    In order to identify good animal models for investigating therapeutic and preventive strategies for pancreatic cancer, we analyzed pancreatic lesions from several transgenic models and made a series of novel findings. Female MT-tgf alpha mice of the MT100 line developed pancreatic proliferation, acinar-ductal metaplasia, multilocular cystic neoplasms, ductal adenocarcinomas and prominent fibrosis, while the lesions in males were less severe. MT-tgf alpha-ES transgenic lines of both sexes developed slowly progressing lesions that were similar to what was seen in MT100 males. In both MT100 and MT-tgf alpha-ES lines, TGF alpha transgene was expressed mainly in proliferating ductal cells. Ela-myc transgenic mice with a mixed C57BL/6, SJL and FVB genetic background developed pancreatic tumors at 2-7 months of age, and half of the tumors were ductal adenocarcinomas, similar to what was reported originally by Sandgren et al 1. However, in 20% of the mice, the tumors metastasized to the liver. MT100/Ela-myc and MT-tgf alpha-ES/Ela-myc double transgenic mice developed not only acinar carcinomas and mixed carcinomas as previously reported but also various ductal-originated lesions, including multilocular cystic neoplasms and ductal adenocarcinomas. The double transgenic tumors were more malignant and metastasized to the liver at a higher frequency (33%) compared with the Ela-myc tumors. Sequencing of the coding region of p16ink4, k-ras and Rb cDNA in small numbers of pancreatic tumors did not identify mutations. The short latency for tumor development, the variety of tumor morphology and the liver metastases seen in Ela-myc and MT-tgf alpha/Ela-myc mice make these animals good models for investigating new therapeutic and preventive strategies for pancreatic cancer.

  14. Variations in the expression and distribution pattern of AQP5 in acinar cells of patients with sialadenosis.

    Science.gov (United States)

    Teymoortash, Afshin; Wiegand, Susanne; Borkeloh, Martin; Bette, Michael; Ramaswamy, Annette; Steinbach-Hundt, Silke; Neff, Andreas; Werner, Jochen A; Mandic, Robert

    2012-01-01

    Previously, we pointed out on a possible role of aquaporin 5 (AQP5) in the development of sialadenosis. The goal of the present study was to further assess the association of AQP5 in the development of this salivary gland disease. The acinar diameter and mean surface area appeared elevated in sialadenosis tissues, which is a typical observation in this disease. AQP5 expression was evaluated by immunohistochemistry using tissue samples derived from salivary glands of patients with confirmed sialadenosis either as a primary diagnosis or as a secondary diagnosis within the framework of other salivary gland diseases. Normal salivary gland tissue served as a control. In sialadenosis tissues, the AQP5 signal at the apical plasma membrane of acinar cells frequently appeared stronger compared with that in normal salivary glands. In addition, the distribution of AQP5 at the apical region seemed to differ between normal and sialadenosis tissues, where AQP5 frequently was diffusely distributed near or at the apical plasma membrane of the acinar cells in contrast to normal controls where the AQP5 signal was strictly confined to the apical plasma membrane. These observations suggest that sialadenosis is associated with a different AQP5 expression and distribution pattern in salivary acinar cells.

  15. Long-term dexamethasone treatment alters the histomorphology of acinar cells in rat parotid and submandibular glands.

    Science.gov (United States)

    Bighetti, Bruna B; d Assis, Gerson F; Vieira, Danilo C; Violato, Natalia M; Cestari, Tania M; Taga, Rumio; Bosqueiro, José R; Rafacho, Alex

    2014-10-01

    Glucocorticoids (GCs) induce insulin resistance (IR), a condition known to alter oral homeostasis. This study investigated the effects of long-term dexamethasone administration on morphofunctional aspects of salivary glands. Male Wistar rats received daily injections of dexamethasone [0.1 mg/kg body weight (b.w.), intraperitoneally] for 10 days (DEX), whereas control rats received saline. Subsequently, glycaemia, insulinaemia, insulin secretion and salivary flow were analysed. The parotid and submandibular glands were collected for histomorphometric evaluation and Western blot experiments. The DEX rats were found to be normoglycaemic, hyperinsulinaemic, insulin resistant and glucose intolerant (P glands (P salivary flux rate. The hypotrophy in both glands observed in the DEX group was associated with marked reduction in the volume of the acinar cells in these glands of 50% and 26% respectively (P acinar cells was increased in the submandibular glands of the DEX rats (P glands. The levels of proteins related to insulin and survival signalling in both glands did not differ between the groups. In conclusion, the long-term administration of dexamethasone caused IR, which was associated with significant reductions in both mass and flux rate of the salivary glands. The parotid and submandibular glands exhibited reduced acinar cell volume; however, the submandibular glands displayed acinar hyperplasia, indicating a gland-specific response to GCs. Our data emphasize that GC-based therapies and insulin-resistant states have a negative impact on salivary gland homeostasis.

  16. Hereditary chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Mössner Joachim

    2007-01-01

    Full Text Available Abstract Hereditary chronic pancreatitis (HCP is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2, the serine protease inhibitor, Kazal type 1 (SPINK1 and the cystic fibrosis transmembrane conductance regulator (CFTR have been found to be associated with chronic pancreatitis (idiopathic and hereditary as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer.

  17. Hereditary pancreatitis: current perspectives

    Directory of Open Access Journals (Sweden)

    Raphael KL

    2016-07-01

    Full Text Available Kara L Raphael, Field F Willingham Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA Abstract: Hereditary pancreatitis (HP is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy. Keywords: pancreatic cancer, chronic pancreatitis, idiopathic pancreatitis, pancreatitis, familial pancreatitis, genetic mutations

  18. Up-regulation of Store-operated Ca2+ Entry and Nuclear Factor of Activated T Cells Promote the Acinar Phenotype of the Primary Human Salivary Gland Cells.

    Science.gov (United States)

    Jang, Shyh-Ing; Ong, Hwei Ling; Liu, Xibao; Alevizos, Ilias; Ambudkar, Indu S

    2016-04-15

    The signaling pathways involved in the generation and maintenance of exocrine gland acinar cells have not yet been established. Primary human salivary gland epithelial cells, derived from salivary gland biopsies, acquired an acinar-like phenotype when the [Ca(2+)] in the serum-free medium (keratinocyte growth medium, KGM) was increased from 0.05 mm (KGM-L) to 1.2 mm (KGM-H). Here we examined the mechanism underlying this Ca(2+)-dependent generation of the acinar cell phenotype. Compared with cells in KGM-L, those in KGM-H display enhancement of Orai1, STIM1, STIM2, and nuclear factor of activated T cells 1 (NFAT1) expression together with an increase in store-operated Ca(2+) entry (SOCE), SOCE-dependent nuclear translocation of pGFP-NFAT1, and NFAT-dependent but not NFκB-dependent gene expression. Importantly, AQP5, an acinar-specific protein critical for function, is up-regulated in KGM-H via SOCE/NFAT-dependent gene expression. We identified critical NFAT binding motifs in the AQP5 promoter that are involved in Ca(2+)-dependent up-regulation of AQP5. These important findings reveal that the Ca(2+)-induced switch of salivary epithelial cells to an acinar-like phenotype involves remodeling of SOCE and NFAT signaling, which together control the expression of proteins critically relevant for acinar cell function. Our data provide a novel strategy for generating and maintaining acinar cells in culture.

  19. Parp-1 genetic ablation in Ela-myc mice unveils novel roles for Parp-1 in pancreatic cancer.

    Science.gov (United States)

    Martínez-Bosch, Neus; Iglesias, Mar; Munné-Collado, Jessica; Martínez-Cáceres, Carlos; Moreno, Mireia; Guerra, Carmen; Yélamos, Jose; Navarro, Pilar

    2014-10-01

    Pancreatic cancer has a dismal prognosis and is currently the fourth leading cause of cancer-related death in developed countries. The inhibition of poly(ADP-ribose) polymerase-1 (Parp-1), the major protein responsible for poly(ADP-ribosy)lation in response to DNA damage, has emerged as a promising treatment for several tumour types. Here we aimed to elucidate the involvement of Parp-1 in pancreatic tumour progression. We assessed Parp-1 protein expression in normal, preneoplastic and pancreatic tumour samples from humans and from K-Ras- and c-myc-driven mouse models of pancreatic cancer. Parp-1 was highly expressed in acinar cells in normal and cancer tissues. In contrast, ductal cells expressed very low or undetectable levels of this protein, both in a normal and in a tumour context. The Parp-1 expression pattern was similar in human and mouse samples, thereby validating the use of animal models for further studies. To determine the in vivo effects of Parp-1 depletion on pancreatic cancer progression, Ela-myc-driven pancreatic tumour development was analysed in a Parp-1 knock-out background. Loss of Parp-1 resulted in increased tumour necrosis and decreased proliferation, apoptosis and angiogenesis. Interestingly, Ela-myc:Parp-1(-/-) mice displayed fewer ductal tumours than their Ela-myc:Parp-1(+/+) counterparts, suggesting that Parp-1 participates in promoting acinar-to-ductal metaplasia, a key event in pancreatic cancer initiation. Moreover, impaired macrophage recruitment can be responsible for the ADM blockade found in the Ela-myc:Parp-1(-/-) mice. Finally, molecular analysis revealed that Parp-1 modulates ADM downstream of the Stat3-MMP7 axis and is also involved in transcriptional up-regulation of the MDM2, VEGFR1 and MMP28 cancer-related genes. In conclusion, the expression pattern of Parp-1 in normal and cancer tissue and the in vivo functional effects of Parp-1 depletion point to a novel role for this protein in pancreatic carcinogenesis and shed light

  20. Endoscopic pancreatic duct stent placement for inflammatory pancreatic diseases

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    The role of endoscopic therapy in the management of pancreatic diseases is continuously evolving; at present most pathological conditions of the pancreas are successfully treated by endoscopic retrograde cholangiopancreatography (ERCP) or endoscopic ultrasound (EUS),or both. Endoscopic placement of stents has played and still plays a major role in the treatment of chronic pancreatitis, pseudocysts, pancreas divisum, main pancreatic duct injuries, pancreatic fistulae, complications of acute pancreatitis, recurrent idiopathic pancreatitis,and in the prevention of post-ERCP pancreatitis. These stents are currently routinely placed to reduce intraductal hypertension, bypass obstructing stones, restore lumen patency in cases with dominant, symptomatic strictures,seal main pancreatic duct disruption, drain pseudocysts or fluid collections, treat symptomatic major or minor papilla sphincter stenosis, and prevent procedure-induced acute pancreatitis. The present review aims at updating and discussing techniques, indications, and results of endoscopic pancreatic duct stent placement in acute and chronic inflammatory diseases of the pancreas.

  1. A systems biology approach identifies a regulatory network in parotid acinar cell terminal differentiation.

    Directory of Open Access Journals (Sweden)

    Melissa A Metzler

    Full Text Available The transcription factor networks that drive parotid salivary gland progenitor cells to terminally differentiate, remain largely unknown and are vital to understanding the regeneration process.A systems biology approach was taken to measure mRNA and microRNA expression in vivo across acinar cell terminal differentiation in the rat parotid salivary gland. Laser capture microdissection (LCM was used to specifically isolate acinar cell RNA at times spanning the month-long period of parotid differentiation.Clustering of microarray measurements suggests that expression occurs in four stages. mRNA expression patterns suggest a novel role for Pparg which is transiently increased during mid postnatal differentiation in concert with several target gene mRNAs. 79 microRNAs are significantly differentially expressed across time. Profiles of statistically significant changes of mRNA expression, combined with reciprocal correlations of microRNAs and their target mRNAs, suggest a putative network involving Klf4, a differentiation inhibiting transcription factor, which decreases as several targeting microRNAs increase late in differentiation. The network suggests a molecular switch (involving Prdm1, Sox11, Pax5, miR-200a, and miR-30a progressively decreases repression of Xbp1 gene transcription, in concert with decreased translational repression by miR-214. The transcription factor Xbp1 mRNA is initially low, increases progressively, and may be maintained by a positive feedback loop with Atf6. Transfection studies show that Xbp1 activates the Mist1 promoter [corrected]. In addition, Xbp1 and Mist1 each activate the parotid secretory protein (Psp gene, which encodes an abundant salivary protein, and is a marker of terminal differentiation.This study identifies novel expression patterns of Pparg, Klf4, and Sox11 during parotid acinar cell differentiation, as well as numerous differentially expressed microRNAs. Network analysis identifies a novel stemness arm, a

  2. Tmem16A encodes the Ca2+-activated Cl- channel in mouse submandibular salivary gland acinar cells.

    Science.gov (United States)

    Romanenko, Victor G; Catalán, Marcelo A; Brown, David A; Putzier, Ilva; Hartzell, H Criss; Marmorstein, Alan D; Gonzalez-Begne, Mireya; Rock, Jason R; Harfe, Brian D; Melvin, James E

    2010-04-23

    Activation of an apical Ca(2+)-dependent Cl(-) channel (CaCC) is the rate-limiting step for fluid secretion in many exocrine tissues. Here, we compared the properties of native CaCC in mouse submandibular salivary gland acinar cells to the Ca(2+)-gated Cl(-) currents generated by Tmem16A and Best2, members from two distinct families of Ca(2+)-activated Cl(-) channels found in salivary glands. Heterologous expression of Tmem16A and Best2 transcripts in HEK293 cells produced Ca(2+)-activated Cl(-) currents with time and voltage dependence and inhibitor sensitivity that resembled the Ca(2+)-activated Cl(-) current found in native salivary acinar cells. Best2(-/-) and Tmem16A(-/-) mice were used to further characterize the role of these channels in the exocrine salivary gland. The amplitude and the biophysical footprint of the Ca(2+)-activated Cl(-) current in submandibular gland acinar cells from Best2-deficient mice were the same as in wild type cells. Consistent with this observation, the fluid secretion rate in Best2 null mice was comparable with that in wild type mice. In contrast, submandibular gland acinar cells from Tmem16A(-/-) mice lacked a Ca(2+)-activated Cl(-) current and a Ca(2+)-mobilizing agonist failed to stimulate Cl(-) efflux, requirements for fluid secretion. Furthermore, saliva secretion was abolished by the CaCC inhibitor niflumic acid in wild type and Best2(-/-) mice. Our results demonstrate that both Tmem16A and Best2 generate Ca(2+)-activated Cl(-) current in vitro with similar properties to those expressed in native cells, yet only Tmem16A appears to be a critical component of the acinar Ca(2+)-activated Cl(-) channel complex that is essential for saliva production by the submandibular gland.

  3. Nutrition, Inflammation, and Acute Pancreatitis

    OpenAIRE

    Max Petrov

    2013-01-01

    Acute pancreatitis is acute inflammatory disease of the pancreas. Nutrition has a number of anti-inflammatory effects that could affect outcomes of patients with pancreatitis. Further, it is the most promising nonspecific treatment modality in acute pancreatitis to date. This paper summarizes the best available evidence regarding the use of nutrition with a view of optimising clinical management of patients with acute pancreatitis.

  4. Pancreatic panniculitis: a cutaneous manifestation of acute pancreatitis

    OpenAIRE

    Laureano, A; Mestre, T; Ricardo, L; Rodrigues, AM; Cardoso, J.

    2014-01-01

    Pancreatic panniculitis is a rare disease in which necrosis of fat in the panniculus and other distant foci occurs in the setting of pancreatic diseases; these diseases include acute and chronic pancreatitis, pancreatic carcinoma, pseudocyst, and other pancreatic diseases. This malady is manifested as tender erythematous nodules on the legs, buttock, or trunk. Histopathologically, it shows the pathognomonic findings of focal subcutaneous fat necrosis and ghost-like anucleated cells with a thi...

  5. Coexistence of Pancreatic Carcinoma and Pancreatic Tuberculosis: Case Report

    OpenAIRE

    Zheng, Zhen-Jiang; Zhang, Hao; Xiang, Guang-Ming; Gong, Jun; Mai, Gang; Liu, Xu-Bao

    2011-01-01

    Pancreatic tuberculosis (TB) is extremely rare and mimics pancreatic carcinoma both clinically and radiologically. This paper discusses the occurrence of 2 heterogeneous masses located in the head and tail of the pancreas in an adult male. In this patient, laparotomy was performed because of the high suspicion of pancreatic carcinoma. Intraoperative fine needle aspiration biopsy revealed the coexistence of pancreatic carcinoma with pancreatic TB, and a combined resection of the distal pancrea...

  6. Fatal Pancreatic Panniculitis Associated with Acute Pancreatitis: A Case Report

    OpenAIRE

    Lee, Woo Sun; Kim, Mi Yeon; Kim, Sang Woo; Paik, Chang Nyol; Kim, Hyung Ok; Park, Young Min

    2007-01-01

    Pancreatic panniculitis is a rare disease in which necrosis of fat in the panniculus and other distant foci occurs in the setting of pancreatic diseases; these diseases include acute and chronic pancreatitis, pancreatic carcinoma, pseudocyst, and other pancreatic diseases. This malady is manifested as tender erythematous nodules on the legs, buttock, or trunk. Histopathologically, it shows the pathognomonic findings of focal subcutaneous fat necrosis and ghost-like anucleated cells with a thi...

  7. Pancreatic and pulmonary mast cells activation during experimental acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Inmaculada; Lopez-Font; Sabrina; Gea-Sorlí; Enrique; de-Madaria; Luis; M; Gutiérrez; Miguel; Pérez-Mateo; Daniel; Closa

    2010-01-01

    AIM:To study the activation of pancreatic and pulmonary mast cells and the effect of mast cell inhibition on the activation of peritoneal and alveolar macrophages during acute pancreatitis.METHODS:Pancreatitis was induced by intraductal infusion of 5% sodium taurodeoxycholate in rats.The mast cell inhibitor cromolyn was administered intraperitoneally(i.p.) 30 min before pancreatitis induction.The pancreatic and pulmonary tissue damage was evaluated histologically and mast cells and their state of activation...

  8. Activation-Induced Cytidine Deaminase Contributes to Pancreatic Tumorigenesis by Inducing Tumor-Related Gene Mutations.

    Science.gov (United States)

    Sawai, Yugo; Kodama, Yuzo; Shimizu, Takahiro; Ota, Yuji; Maruno, Takahisa; Eso, Yuji; Kurita, Akira; Shiokawa, Masahiro; Tsuji, Yoshihisa; Uza, Norimitsu; Matsumoto, Yuko; Masui, Toshihiko; Uemoto, Shinji; Marusawa, Hiroyuki; Chiba, Tsutomu

    2015-08-15

    Pancreatic ductal adenocarcinoma (PDAC) develops via an accumulation of various gene mutations. The mechanism underlying the mutations in PDAC development, however, is not fully understood. Recent insight into the close association between the mutation pattern of various cancers and specific mutagens led us to investigate the possible involvement of activation-induced cytidine deaminase (AID), a DNA editing enzyme, in pancreatic tumorigenesis. Our immunohistochemical findings revealed AID protein expression in human acinar ductal metaplasia, pancreatic intraepithelial neoplasia, and PDAC. Both the amount and intensity of the AID protein expression increased with the progression from precancerous to cancerous lesions in human PDAC tissues. To further assess the significance of ectopic epithelial AID expression in pancreatic tumorigenesis, we analyzed the phenotype of AID transgenic (AID Tg) mice. Consistent with our hypothesis that AID is involved in the mechanism of the mutations underlying pancreatic tumorigenesis, we found precancerous lesions developing in the pancreas of AID Tg mice. Using deep sequencing, we also detected Kras and c-Myc mutations in our analysis of the whole pancreas of AID Tg mice. In addition, Sanger sequencing confirmed the presence of Kras, c-Myc, and Smad4 mutations, with the typical mutational footprint of AID in precancerous lesions in AID Tg mice separated by laser capture microdissection. Taken together, our findings suggest that AID contributes to the development of pancreatic precancerous lesions by inducing tumor-related gene mutations. Our new mouse model without intentional manipulation of specific tumor-related genes provides a powerful system for analyzing the mutations involved in PDAC.

  9. Treatment of acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Al-Mofleh Ibrahim

    1998-01-01

    Full Text Available There is no specific treatment for acute pancreatitis. Majority of patients with acute pancreatitis respond to medical therapy. Supportive measures and close observations represent the cornerstone of the medical therapy. Failure to respond to medical treatment may indicate choledocholithiasis or infected necrosis. Endoscopic papillotomy with stone retrieval is beneficial in patients with severe biliary pancreatitis. Image-guided fine needle aspiration and bacteriological examination of aspirate is reliable in detecting infection and deliniating causative pathogen. Surgical debridement is the method of choice for treatment of infected necrosis. In contrast, in pancreatic abscess, surgery is preserved for those, who do not respond to percutaneous drainage combined with antibiotics. The benefit of antisecretory and antiproteolytic agents is debatable. A combination of antioxidants, calcium channel antagonists and antibiotics may play a major role in the treatment of acute pancreatitis in the future.

  10. Review of idiopathic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Recent advances in understanding of pancreatitis and advances in technology have uncovered the veils of idiopathic pancreatitis to a point where a thorough history and judicious use of diagnostic techniques elucidate the cause in over 80% of cases. This review examines the multitude of etiologies of what were once labeled idiopathic pancreatitis and provides the current evidence on each. This review begins with a background review of the current epidemiology of idiopathic pancreatitis prior to discussion of various etiologies. Etiologies of medications, infections, toxins,autoimmune disorders, vascular causes, and anatomic and functional causes are explored in detail. We conclude with management of true idiopathic pancreatitis and a summary of the various etiologic agents. Throughout this review, areas of controversies are highlighted.

  11. Insulin is necessary for the hypertrophic effect of cholecystokinin-octapeptide following acute necrotizing experimental pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Péter Hegyi; Zoltán Rakonczay Jr; Réka Sári; László Czakó; Norbert Farkas; Csaba Góg; József Németh; János Lonovics; Tamás Takács

    2004-01-01

    AIM: In previous experiments we have demonstrated that by administering low doses of cholecystokinin-octapeptide (CCK-8), the process of regeneration following L-arginine (Arg)-induced pancreatitis is accelerated. In rats that were also diabetic (induced by streptozotocin, STZ), pancreatic regeneration was not observed. The aim of this study was to deduce whether the administration of exogenous insulin could in fact restore the hypertrophic effect of CCK-8 in diabetic-pancreatitic rats.METHODS: Male Wistar rats were used for the experiments.Diabetes mellitus was induced by administering 60 mg/kg body mass of STZ intraperitoneally (i.p.), then, on d 8,pancreatitis was induced by 200 mg/100 g body mass Arg i.p. twice at an interval of 1 h. The animals were injected subcutaneously twice daily (at 7 a.m. and 7 p.m.) with 1 μg/kg of CCK-8 and/or 2 IU mixed insulin (300 g/L shortaction and 700 g/L intermediate-action insulin) for 14 d after pancreatitis induction. Following this the animals were killed and the serum amylase, glucose and insulin levels as well as the plasma glucagon levels, the pancreatic mass/body mass ratio (pm/bm), the pancreatic contents of DNA, protein, amylase, lipase and trypsinogen were measured. Pancreatic tissue samples were examined by light microscopy on paraffin-embedded sections.RESULTS: In the diabetic-pancreatitic rats treatment with insulin and CCK-8 significantly elevated pw/bm and the pancreatic contents of protein, amylase and lipase vs the rats receiving only CCK-8 treatment. CCK-8 administered in combination with insulin also elevated the number of acinar cells with mitotic activities, whereas CCK-8 alone had no effect on laboratory parameters or the mitotic activities in diabetic-pancreatitic rats.CONCLUSION: Despite the hypertrophic effect of CCK-8 being absent following acute pancreatitis in diabetic-rats,the simultaneous administration of exogenous insulin restored this effect. Our results clearly demonstrate that insulin is

  12. Pancreatic Involvement in Melioidosis

    Directory of Open Access Journals (Sweden)

    Vui Heng Chong

    2010-07-01

    Full Text Available Context Melioidosis is endemic to tropical regions and, despite the common occurrence of intra-abdominal abscesses, pancreatic involvement in melioidosis has not previously been reported. Objective We report our experience with pancreatic melioidosis. Patients All 65 patients treated for melioidosis who had computed tomography (CT scans were identified from prospective databases and were retrospectively reviewed. Main outcome measures A detailed review of cases with pancreas involvement was carried out. Results There were four cases (three males and one female; median age 29.5 years, range: 25-48 years with pancreatic melioidosis, giving a prevalence of 6.2%. All had predisposing conditions (two had poorly controlled diabetes mellitus and two had thalassemia for melioidosis. Fever (100%, anorexia (100%, weight loss (100%, rigor (75% and abdominal pain (75% were the most common symptoms at presentation and the median duration of symptoms before presentation was six weeks (range: 2-8 weeks. All pancreatic abscesses were detected on CT scan. Multiple foci involvement was common (3 to 6 sites: blood (4 patients, liver (3 patients, psoas muscle (2 patients, spleen (2 patients, infected ascites (2 patients and lung (1 patient. Pancreatic involvement ranged from multi-focal micro-abscesses to focal large abscesses and involved all parts of the pancreas (body 100%, head 75% and tail 50%. Associated pancreatic findings included splenic vein thrombosis, peripancreatic inflammation and peripancreatic fat streaking. All the pancreatic abscesses were resolved with antibiotics without requiring pancreatic abscess drainage (including one patient who died from disseminated melioidosis. Conclusion Pancreatic involvement typically occurs as part of multi-organ involvement and commonly manifests as multifoci micro-abscesses. Associated pancreatic abnormalities were also common. All responded to treatment without requiring drainage

  13. Sensitization to and Challenge with Gliadin Induce Pancreatitis and Extrapancreatic Inflammation in HLA-DQ8 Mice: An Animal Model of Type 1 Autoimmune Pancreatitis

    Science.gov (United States)

    Moon, Sung-Hoon; Kim, Jihun; Kim, Mi-Young; Park, Do Hyun; Song, Tae Jun; Kim, Sun A; Lee, Sang Soo; Seo, Dong Wan; Lee, Sung Koo; Kim, Myung-Hwan

    2016-01-01

    Background/Aims The aim of this study was to establish a pathogenetic mechanism of pancreatitis in celiac disease and IgG4-related disease using gluten-sensitive human leukocyte antigen (HLA)-DQ8 transgenic mice. Methods Transgenic mice expressing HLA-DQ8 genes were utilized. Control mice were not sensitized but were fed gliadin-free rice cereal. Experimental groups consisted of gliadin-sensitized and gliadin-challenged mice; nonsensitized mice with cerulein hyperstimulation; and gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation. Results Gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation showed significant inflammatory cell infiltrates, fibrosis and acinar atrophy compared with the control mice and the other experimental groups. The immunohistochemical analysis showed greater IgG1-positive plasma cells in the inflammatory infiltrates of gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation compared with the control mice and the other experimental groups. Gliadin-sensitized and gliadin-challenged mice with cerulein hyperstimulation or gliadin-sensitized and gliadin-challenged mice showed IgG1-stained inflammatory cell infiltrates in the extrapancreatic organs, including the bile ducts, salivary glands, kidneys, and lungs. Conclusions Gliadin-sensitization and cerulein hyperstimulation of gluten-sensitive HLA-DQ8 transgenic mice resulted in pancreatitis and extrapancreatic inflammation. This animal model suggests that chronic gliadin ingestion in a susceptible individual with the HLA-DQ8 molecule may be associated with pancreatitis and extrapancreatic inflammation. PMID:27114422

  14. Chronic pancreatitis and pancreatic cancer; the clinical aspects and treatment of pancreatic exocrine insufficiency

    NARCIS (Netherlands)

    E.C.M. Sikkens (Edmée)

    2013-01-01

    textabstractIn exocrine pancreatic insufficiency, the pancreas is unable to deliver a sufficient quantity of pancreatic enzymes to the small intestine to digest food. It may occur in several life threatening diseases, including chronic pancreatitis and pancreatic cancer. Due to this lack or absence

  15. The Acinar Cage: Basement Membranes Determine Molecule Exchange and Mechanical Stability of Human Breast Cell Acini.

    Directory of Open Access Journals (Sweden)

    Aljona Gaiko-Shcherbak

    Full Text Available The biophysical properties of the basement membrane that surrounds human breast glands are poorly understood, but are thought to be decisive for normal organ function and malignancy. Here, we characterize the breast gland basement membrane with a focus on molecule permeation and mechanical stability, both crucial for organ function. We used well-established and nature-mimicking MCF10A acini as 3D cell model for human breast glands, with ether low- or highly-developed basement membrane scaffolds. Semi-quantitative dextran tracer (3 to 40 kDa experiments allowed us to investigate the basement membrane scaffold as a molecule diffusion barrier in human breast acini in vitro. We demonstrated that molecule permeation correlated positively with macromolecule size and intriguingly also with basement membrane development state, revealing a pore size of at least 9 nm. Notably, an intact collagen IV mesh proved to be essential for this permeation function. Furthermore, we performed ultra-sensitive atomic force microscopy to quantify the response of native breast acini and of decellularized basement membrane shells against mechanical indentation. We found a clear correlation between increasing acinar force resistance and basement membrane formation stage. Most important native acini with highly-developed basement membranes as well as cell-free basement membrane shells could both withstand physiologically relevant loads (≤ 20 nN without loss of structural integrity. In contrast, low-developed basement membranes were significantly softer and more fragile. In conclusion, our study emphasizes the key role of the basement membrane as conductor of acinar molecule influx and mechanical stability of human breast glands, which are fundamental for normal organ function.

  16. [Etiological factors of acute pancreatitis].

    Science.gov (United States)

    Spicák, J

    2002-09-01

    Acute pancreatitis develops immediately after the causative impulse, while chronic pancreatitis develops after the long-term action of the noxious agent. A typical representative of acute pancreatitis is biliary pancreatitis, chronic pancreatitis develops in alcoholism and has a long latency. As alcoholic pancreatitis is manifested at first as a rule by a potent attack, it is classified in this stage as acute pancreatitis. The most frequent etiological factors in our civilization are thus cholelithiasis and alcoholism (both account for 20-50% in different studies). The assumed pathogenetic principles in acute biliary pancreatitis are the common canal of both efferent ducts above the obturated papilla, duodenopancreatic reflux and intrapancreatic hypertension. A detailed interpretation is however lacking. The pathogenesis of alcoholic pancreatitis is more complicated. Among others some part is played by changes in the calcium concentration and fusion of cellular membranes. Idiopathic pancreatitis occurs in up to 10%, part of the are due to undiagnosed alcoholism and cholelithiasis. Other etiologies are exceptional. Similarly as in cholelithiasis pancreatitis develops also during other pathological processes in the area of the papilla of Vater such as dysfunction of the sphincter of Oddi, ampulloma and juxtapapillary diverticulum, it is however usually mild. The incidence of postoperative pancreatitis is declining. Its lethality is 30% and the diagnosis is difficult. In the pathogenesis changes of the ion concentration are involved, hypoxia and mechanical disorders of the integrity of the gland. Pancreatitis develops in association with other infections--frequently in mumps, rarely in hepatitis, tuberculosis, typhoid and mycoses. Viral pancreatitis is usually mild. In parasitoses pancreatitis develops due to a block of the papilla Vateri. In hyperparathyroidism chronic pancreatitis is more likely to develop, recent data are lacking. As to dyslipoproteinaemias

  17. [Etiological factors of acute pancreatitis].

    Science.gov (United States)

    Spicák, J

    2002-09-01

    Acute pancreatitis develops immediately after the causative impulse, while chronic pancreatitis develops after the long-term action of the noxious agent. A typical representative of acute pancreatitis is biliary pancreatitis, chronic pancreatitis develops in alcoholism and has a long latency. As alcoholic pancreatitis is manifested at first as a rule by a potent attack, it is classified in this stage as acute pancreatitis. The most frequent etiological factors in our civilization are thus cholelithiasis and alcoholism (both account for 20-50% in different studies). The assumed pathogenetic principles in acute biliary pancreatitis are the common canal of both efferent ducts above the obturated papilla, duodenopancreatic reflux and intrapancreatic hypertension. A detailed interpretation is however lacking. The pathogenesis of alcoholic pancreatitis is more complicated. Among others some part is played by changes in the calcium concentration and fusion of cellular membranes. Idiopathic pancreatitis occurs in up to 10%, part of the are due to undiagnosed alcoholism and cholelithiasis. Other etiologies are exceptional. Similarly as in cholelithiasis pancreatitis develops also during other pathological processes in the area of the papilla of Vater such as dysfunction of the sphincter of Oddi, ampulloma and juxtapapillary diverticulum, it is however usually mild. The incidence of postoperative pancreatitis is declining. Its lethality is 30% and the diagnosis is difficult. In the pathogenesis changes of the ion concentration are involved, hypoxia and mechanical disorders of the integrity of the gland. Pancreatitis develops in association with other infections--frequently in mumps, rarely in hepatitis, tuberculosis, typhoid and mycoses. Viral pancreatitis is usually mild. In parasitoses pancreatitis develops due to a block of the papilla Vateri. In hyperparathyroidism chronic pancreatitis is more likely to develop, recent data are lacking. As to dyslipoproteinaemias

  18. Updates on Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Ojas Vyas

    2014-05-01

    Full Text Available Pancreatic adenocarcinoma remains a therapeutic challenge. The American Cancer Society estimates that in 2014 about 46,420 people will be diagnosed with pancreatic cancer and about 39,590 people will die of pancreatic cancer in the United States [1]. The incidence of pancreatic carcinoma has markedly increased over the past several decades and it now ranks as the fourth leading cause of cancer-related death in the United States. Despite the high mortality rate associated with pancreatic cancer, its etiology is poorly understood. Although progress in the development of new cytotoxic and biological drugs for the treatment of pancreatic cancer continues, the outcome remains grim. Many organizations and associations have taken an effort to improve knowledge, understanding and outcome of patients with pancreatic cancer. Pancreas Club, since its founding in 1966, is aimed to promote the interchange of ideas between physicians and scientists focused on pancreas throughout the world in an informal “club” atmosphere. We attended the 48th Annual Meeting of Pancreas Club in Chicago and reviewed many interesting posters and oral presentations. Here we discuss a few selected abstracts.

  19. Familial pancreatic cancer.

    Science.gov (United States)

    Klein, A P; Hruban, R H; Brune, K A; Petersen, G M; Goggins, M

    2001-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States and will be responsible for an estimated 28,900 deaths in 2001. Relatively little is known of its etiology, and the only well-established risk factor is cigarette smoking. Studies over the past 3 decades have shown that 4%-16% of patients with pancreatic cancer have a family history of the disease. A small fraction of this aggregation can be accounted for in inherited cancer syndromes, including familial atypical multiple-mole melanoma, Peutz-Jeghers syndrome, hereditary breast-ovarian cancer, hereditary pancreatitis, and hereditary nonpolyposis colorectal cancer. These syndromes arise as a result of germline mutations in the BRCA2, pl6 (familial atypical multiple-mole melanoma), mismatch repair (hereditary nonpolyposis colorectal cancer), and STK11 (Peutz-Jeghers syndrome) genes. In addition, hereditary plays a role in predisposing certain patients with apparently sporadic pancreatic cancer. Many patients with pancreatic cancers caused by a germline mutation in a cancer-causing gene do not have a pedigree that is suggestive of a familial cancer syndrome. A recent prospective analysis of the pedigrees in the National Familial Pancreatic Tumor Registry found that individuals with a family history of pancreatic cancer in multiple first-degree relatives have a high risk of pancreatic cancer themselves. The identification of such high-risk individuals will help clinicians target screening programs and develop preventive interventions with the hope of reducing the mortality of pancreatic cancer in these families.

  20. Can Pancreatic Cancer Be Found Early?

    Science.gov (United States)

    ... Topic Signs and symptoms of pancreatic cancer Can pancreatic cancer be found early? Pancreatic cancer is hard to ... Testing: What You Need to Know . Testing for pancreatic cancer in people at high risk For people in ...

  1. Researchers Identify Early Sign of Pancreatic Cancer

    Science.gov (United States)

    ... of pancreatic cancer Researchers identify early sign of pancreatic cancer September 28, 2014 Tags: PancreaticCancer Brian Wolpin, MD ... discovered a sign of the early development of pancreatic cancer – an upsurge in certain amino acids that occurs ...

  2. Pancreatitis in scrub typhus

    Directory of Open Access Journals (Sweden)

    Alok Bhatt

    2014-01-01

    Full Text Available Scrub typhus is a rickettsial infection prevalent in most parts of India. Acute pancreatitis with pseudocyst formation is a rare complication of this condition. This paper reports acute renal failure, pancreatitis and pseudocyst formation in a 48-year-old female with scrub typhus. Ultrasonography of the abdomen revealed a bulky pancreas with fluid seen along the body of the pancreas in the lesser sac. The infection was successfully treated with doxycycline and supportive treatment. Pancreatitis was managed conservatively. This case report highlights the importance of identifying and managing uncommon complications of a common tropical disease for optimum outcome.

  3. Delayed internal pancreatic fistula with pancreatic pleural effusion postsplenectomy

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The occurrence of pancreatic pleural effusion,secondary to an internal pancreatic fistula,is a rare clinical syndrome and diagnosis is often missed.The key to the diagnosis is a dramatically elevated pleural fluid amylase.This pancreatic pleural effusion is also called a pancreatic pleural fistula.It is characterized by profuse pleural fluid and has a tendency to recur.Here we report a case of delayed internal pancreatic fistula with pancreatic pleural effusion emerging after splenectomy.From the treatment ...

  4. Expression of early growth response factor-1 in rats with cerulein-induced acute pancreatitis and its significance

    Institute of Scientific and Technical Information of China (English)

    Lan-Bo Gong; Li He; Yang Liu; Xue-Qing Chen; Bo Jiang

    2005-01-01

    AIM: To observe the expressions of early growth response factor-1 (Egr-L) and tissue factor (TF) in rats with cerulein-induced acute pancreatitis and to explore its significance.METHODS: A large dose of cerulein was used to create the experimental acute pancreatitis model in rats. The changes of Egr-1 mRNA and protein in rats were observed during 30 min to 4 h after the treatment and immunohistochemical method was used to observe the localized expression of Egr-1 in tissues. In addition to the mRNA expression of Egr-1 target gene, TF was also observed. A blank control group, and a bombesinadministered group were used for comparison.RESULTS: After the stimulation of a large dose of cerulein,the rats showed typical inflammatory changes of acute pancreatitis. Thirty minutes after the stimulation, the mRNA expression of Egr-1 in the pancreatic tissue reached its peak and then declined, while the expression of Egr-1protein reached its peak 2 h after the stimulation.Histologically, 2 h after the stimulation, almost all pancreatic acinar cells had the expression of Egr-1 protein,which was focused in the nuclei. The mRNA expression of TF occurred 1 h after the stimulation and gradually increased within 4 h. However, a large dose of bombesin only stimulated the pancreatic tissue to produce a little mRNA expression of Egr-1 and no mRNA expression of Egr-1 protein and TF.CONCLUSION: Egr-1 as a pro-inflammatory transcription factor may play an important role in the pathogenesis of acute pancreatitis by modulating the expression of TF.

  5. Increase in muscarinic stimulation-induced Ca(2+) response by adenovirus-mediated Stim1-mKO1 gene transfer to rat submandibular acinar cells in vivo.

    Science.gov (United States)

    Morita, Takao; Nezu, Akihiro; Tojyo, Yosuke; Tanimura, Akihiko

    2013-10-01

    Adenoviruses have been used for gene transfer to salivary gland cells in vivo. Their use to study the function of salivary acinar cells was limited by a severe inflammatory response and by the destruction of fluid-secreting acinar cells. In the present study, low doses of adenovirus were administered to express Stim1-mKO1 by retrograde ductal injection to submandibular glands. The approach succeeded in increasing muscarinic stimulation-induced Ca(2+) responses in acinar cells without inflammation or decreased salivary secretions. This increased Ca(2+) response was notable upon weak muscarinic stimulation and was attributed to increased Ca(2+) release from internal stores and increased Ca(2+) entry. The basal Ca(2+) level was higher in Stim1-mKO1-expressing cells than in mKO1-expressing and non-expressing cells. Exposure of permeabilized submandibular acinar cells, where Ca(2+) concentration was fixed at 50 nM, to inositol 1,4,5-trisphosphate (IP3) produced similar effects on the release of Ca(2+) from stores in Stim1-mKO1-expressing and non-expressing cells. The low toxicity and relative specificity to acinar cells of the mild gene transfer method described herein are particularly useful for studying the molecular functions of salivary acinar cells in vivo, and may be applied to increase salivary secretions in experimental animals and human in future.

  6. Acute pancreatitis in children

    Directory of Open Access Journals (Sweden)

    Jokić Radoica

    2012-01-01

    Full Text Available Introduction. Acute pancreatitis in children is mostly due to abdominal trauma, diseases or congenital anomalies of the biliary-pancreatic tree. Both exogenous and endogenous functions of the gland could be disturbed by various levels of damage. Clinical Finding and Diagnostics. Acute abdominal pain, gastrointestinal signs and general deterioration are the main clinical findings. The examination can be completed by blood and urine tests of amylase, electrolytes level, and the C-reactive protein. In addition to these tests, ultrasound, computed tomography and endoscopy are required as well. Therapeutic Methods. The therapy of choice is non-operative treatment using medicaments to control the pain, decrease the pancreatic activity and prevent further complications. If the conservative treatment fails, the surgical approach is necessary: drainage, resections, by-pass procedures, etc. Conclusion. Acute pancreatitis is a very serious disease in childhood. Clinical experience and rational approach are very important in the diagnostic and therapeutic methods.

  7. Perspectives in Pancreatic Pain

    Directory of Open Access Journals (Sweden)

    A. S. Salim

    1997-01-01

    Full Text Available This review describes some of the mechanisms which are thought to be important in the causation of pain in chronic pancreatitis. Both medical and surgical techniques for treating this pain are described.

  8. Familial Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Stephen J. Lanspa

    2010-11-01

    Full Text Available Pancreatic cancer’s high mortality rate equates closely with its incidence, thereby showing the need for development of biomarkers of its increased risk and a better understanding of its genetics, so that high-risk patients can be better targeted for screening and early potential lifesaving diagnosis. Its phenotypic and genotypic heterogeneity is extensive and requires careful scrutiny of its pattern of cancer associations, such as malignant melanoma associated with pancreatic cancer, in the familial atypical multiple mole melanoma syndrome, due to the CDKN2A germline mutation. This review is designed to depict several of the hereditary pancreatic cancer syndromes with particular attention given to the clinical application of this knowledge into improved control of pancreatic cancer.

  9. Pancreatic islet cell tumor

    Science.gov (United States)

    ... may include: Fasting glucose level Gastrin level Glucose tolerance test Secretin stimulation test for pancreas Blood glucagon ... PhD, and the A.D.A.M. Editorial team. Related MedlinePlus Health Topics Pancreatic Cancer Browse the ...

  10. Acute pancreatitis in pregnancy

    Institute of Scientific and Technical Information of China (English)

    Capecomorin S Pitchumoni; Balaji Yegneswaran

    2009-01-01

    Acute pancreatitis (AP) is a rare event in pregnancy,occurring in approximately 3 in 10 000 pregnancies.The spectrum of AP in pregnancy ranges from mild pancreatitis to serious pancreatitis associated with necrosis, abscesses, pseudocysts and multiple organ dysfunction syndromes. Pregnancy related hematological and biochemical alterations influence the interpretation of diagnostic tests and assessment of severity of AP. As in any other disease associated with pregnancy, AP is associated with greater concerns as it deals with two lives rather than just one as in the nonpregnant population. The recent advances in clinical gastroenterology have improved the early diagnosis and effective management of biliary pancreatitis. Diagnostic studies such as endoscopic ultrasound,magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography and therapeutic modalities that include endoscopic sphincterotomy, biliary stenting, common bile duct stone extraction and laparoscopic cholecystectomy are major milestones in gastroenterology. When properly managed AP in pregnancy does not carry a dismal prognosis as in the past.

  11. What Is Pancreatic Cancer?

    Science.gov (United States)

    ... very important to distinguish between exocrine and endocrine cancers of the pancreas. They have distinct risk factors and causes, have ... are by far the most common type of pancreas cancer. If you are told you have pancreatic cancer, ...

  12. Imaging of acute pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Merkle, Elmar M.; Goerich, Johannes [Department of Radiology, University Hospitals of Ulm, Steinhoevel Strasse 9, 89075 Ulm (Germany)

    2002-08-01

    Acute pancreatitis is defined as an acute inflammatory process of the pancreas with variable involvement of peripancreatic tissues or remote organ systems. This article reports the current classification, definition and terminology, epidemiology and etiology, pathogenesis and pathological findings, clinical and laboratory findings, and finally imaging findings of acute pancreatitis with emphasis on cross-sectional imaging modalities such as ultrasound, computed tomography, and magnetic resonance imaging. (orig.)

  13. [Hereditary aspects of pancreatitis].

    Science.gov (United States)

    Bak, Daniel; Sobczyńska-Tomaszewska, Agnieszka; Bal, Jerzy

    2003-01-01

    Pancreatitis presents clinically as acute and chronic form. A common characteristic of these two forms is enzymatic autodigestion of pancreas in the course of the disease. It results from premature activation of pancreatic digestive enzymes and disturbance of subtle balance between proteolytic enzymes and their inhibitors. The way to understand the character of mechanisms leading to development of pancreatitis has been simplified by discovery of genetic factors, which are able to initiate pathological changes at tissue level. Mutations in the PRSS1 gene (first of all R122H and N29I mutations), which encodes for cationic trypsin, cause trypsin to be protected from autodegradation. These mutations also cause precursor of trypsin - trypsinogen, to be activated easier. On the other hand mutations in the SPINK1 gene have been identified. SPINK1 gene encodes for the most important protease inhibitor of the pancreatic fluid. The most frequent mutation, namely N34S, decrease SPINK1 protein in its activity. The link between the genotype and phenotype is not clear in every case. It is probable that pancreatitis will be recognized as poligenic with many genes engaged in the disease development. Pancreatic cancer is a frequent consequence of pancreatitis. It is a very invasive cancer with high mortality. In the course of pancreatic inflammation intensive cell proliferation takes place for regeneration of pancreas damage. It is the chance for amplification of pathological changes in DNA, which have arisen as a ROS's (Reactive Oxygen Species) and RNOS's (Reactive Nitrogen Oxide Species) action effect. ROS and RNOS are generated in the course of pancreas inflammation.

  14. Primary alveolar capillary dysplasia (acinar dysplasia) and surfactant protein B deficiency: a clinical, radiological and pathological study

    Energy Technology Data Exchange (ETDEWEB)

    Hugosson, Claes O.; Khoumais, Nuha [King Faisal Specialist Hospital and Research Centre, Department of Radiology MBC 28, Riyadh (Saudi Arabia); Salama, Husam M.; Kattan, Abdul H. [King Faisal Specialist Hospital and Research Centre, Department of Paediatrics, Riyadh (Saudi Arabia); Al-Dayel, Fouad [King Faisal Specialist Hospital and Research Centre, Department of Pathology, Riyadh (Saudi Arabia)

    2005-03-01

    Full-term infants with severe and prolonged respiratory distress represent a diagnostic challenge. Plain radiographic findings may be nonspecific or similar to classic surfactant deficiency disease for infants with surfactant protein B deficiency and acinar dysplasia. Objectives: To describe the similar clinical-radiolgical patterns of two rare neonatal conditions. Six newborn babies with severe respiratory distress at birth demonstrated clinical and radiographically prolonged and progressive diffuse pulmonary opacification. All infants demonstrated hyperinflation of the lungs. The diffuse hazy opacification, which varied from mild (n=3) to moderate (n=3), progressed to severe diffuse opacification preceding death, which occurred at 12-36 days of life. Open lung biopsy confirmed the diagnosis of primary alveolar acinar dysplasia (AD) in four infants and surfactant protein B deficiency (SPBD) in two infants. In full-term babies with unexplained progressive respiratory distress from birth and progress of radiological changes, both AD and SPBD should be considered. (orig.)

  15. Primary alveolar capillary dysplasia (acinar dysplasia) and surfactant protein B deficiency: a clinical, radiological and pathological study

    International Nuclear Information System (INIS)

    Full-term infants with severe and prolonged respiratory distress represent a diagnostic challenge. Plain radiographic findings may be nonspecific or similar to classic surfactant deficiency disease for infants with surfactant protein B deficiency and acinar dysplasia. Objectives: To describe the similar clinical-radiological patterns of two rare neonatal conditions. Six newborn babies with severe respiratory distress at birth demonstrated clinical and radiographically prolonged and progressive diffuse pulmonary opacification. All infants demonstrated hyperinflation of the lungs. The diffuse hazy opacification, which varied from mild (n=3) to moderate (n=3), progressed to severe diffuse opacification preceding death, which occurred at 12-36 days of life. Open lung biopsy confirmed the diagnosis of primary alveolar acinar dysplasia (AD) in four infants and surfactant protein B deficiency (SPBD) in two infants. In full-term babies with unexplained progressive respiratory distress from birth and progress of radiological changes, both AD and SPBD should be considered. (orig.)

  16. Autoimmune pancreatitis and cholangitis

    Institute of Scientific and Technical Information of China (English)

    Niraj; Jani; James; Buxbaum

    2015-01-01

    Autoimmune pancreatitis(AIP) is part of a systemic fibrosclerotic process characterized by lymphoplasmacytic infiltrate with immunoglobulin G subtype-4(Ig G4) positive cells. It characteristically presents with biliary obstruction due to mass-like swelling of the pancreas. Frequently AIP is accompanied by extra-pancreaticmanifestations including retroperitoneal fibrosis, thyroid disease, and salivary gland involvement. Auto-antibodies, hypergammaglobulemia, and prompt resolution of pancreatic and extrapancreatic findings with steroids signify its autoimmune nature. Refractory cases are responsive to immunomodulators and rituximab. Involvement of the biliary tree, termed IgG 4 associated cholangiopathy, mimics primary sclerosing cholangitis and is challenging to manage. High IgG 4 levels and swelling of the pancreas with a diminutive pancreatic duct are suggestive of autoimmune pancreatitis. Given similarities in presentation but radical differences in management and outcome, differentiation from pancreatic malignancy is of paramount importance. There is controversy regarding the optimal diagnostic criterion and steroid trials to make the diagnosis. Additionally, the retroperitoneal location of the pancreas and requirement for histologic sampling, makes tissue acquisition challenging. Recently, a second type of autoimmune pancreatitis has been recognized with similar clinical presentation and steroid response though different histology, serologic, and extrapancreatic findings.

  17. Uptake and metabolism of D-glucose in isolated acinar and ductal cells from rat submandibular glands.

    Science.gov (United States)

    Cetik, Sibel; Rzajeva, Aigun; Hupkens, Emeline; Malaisse, Willy J; Sener, Abdullah

    2014-07-01

    The present study deals with the possible effects of selected environmental agents upon the uptake and metabolism of d-glucose in isolated acinar and ductal cells from the rat submandibular salivary gland. In acinar cells, the uptake of d-[U-(14) C]glucose and its non-metabolised analogue 3-O-[(14) C-methyl]-d-glucose was not affected significantly by phloridzin (0.1 mM) or substitution of extracellular NaCl (115 mM) by an equimolar amount of CsCl, whilst cytochalasin B (20 μM) decreased significantly such an uptake. In ductal cells, both phloridzin and cytochalasin B decreased the uptake of d-glucose and 3-O-methyl-d-glucose. Although the intracellular space was comparable in acinar and ductal cells, the catabolism of d-glucose (2.8 or 8.3 mM) was two to four times higher in ductal cells than in acinar cells. Phloridzin (0.1 mM), ouabain (1.0 mM) and cytochalasin B (20 μM) all impaired d-glucose catabolism in ductal cells. Such was also the case in ductal cells incubated in the absence of extracellular Ca(2+) or in media in which NaCl was substituted by CsCl. It is proposed that the ductal cells in the rat submandibular gland are equipped with several systems mediating the insulin-sensitive, cytochalasin B-sensitive and phloridzin-sensitive transport of d-glucose across the plasma membrane.

  18. A fluid secretion pathway unmasked by acinar-specific Tmem16A gene ablation in the adult mouse salivary gland.

    Science.gov (United States)

    Catalán, Marcelo A; Kondo, Yusuke; Peña-Munzenmayer, Gaspar; Jaramillo, Yasna; Liu, Frances; Choi, Sooji; Crandall, Edward; Borok, Zea; Flodby, Per; Shull, Gary E; Melvin, James E

    2015-02-17

    Activation of an apical Ca(2+)-activated Cl(-) channel (CaCC) triggers the secretion of saliva. It was previously demonstrated that CaCC-mediated Cl(-) current and Cl(-) efflux are absent in the acinar cells of systemic Tmem16A (Tmem16A Cl(-) channel) null mice, but salivation was not assessed in fully developed glands because Tmem16A null mice die within a few days after birth. To test the role of Tmem16A in adult salivary glands, we generated conditional knockout mice lacking Tmem16A in acinar cells (Tmem16A(-/-)). Ca(2+)-dependent salivation was abolished in Tmem16A(-/-) mice, demonstrating that Tmem16A is obligatory for Ca(2+)-mediated fluid secretion. However, the amount of saliva secreted by Tmem16A(-/-) mice in response to the β-adrenergic receptor agonist isoproterenol (IPR) was comparable to that seen in controls, indicating that Tmem16A does not significantly contribute to cAMP-induced secretion. Furthermore, IPR-stimulated secretion was unaffected in mice lacking Cftr (Cftr(∆F508/∆F508)) or ClC-2 (Clcn2(-/-)) Cl(-) channels. The time course for activation of IPR-stimulated fluid secretion closely correlated with that of the IPR-induced cell volume increase, suggesting that acinar swelling may activate a volume-sensitive Cl(-) channel. Indeed, Cl(-) channel blockers abolished fluid secretion, indicating that Cl(-) channel activity is critical for IPR-stimulated secretion. These data suggest that β-adrenergic-induced, cAMP-dependent fluid secretion involves a volume-regulated anion channel. In summary, our results using acinar-specific Tmem16A(-/-) mice identify Tmem16A as the Cl(-) channel essential for muscarinic, Ca(2+)-dependent fluid secretion in adult mouse salivary glands.

  19. TNF-α inhibits aquaporin 5 expression in human salivary gland acinar cells via suppression of histone H4 acetylation.

    Science.gov (United States)

    Yamamura, Yoshiko; Motegi, Katsumi; Kani, Kouichi; Takano, Hideyuki; Momota, Yukihiro; Aota, Keiko; Yamanoi, Tomoko; Azuma, Masayuki

    2012-08-01

    Sjögren's syndrome is a systemic autoimmune disease characterized by reductions in salivary and lacrimal secretions. The mechanisms underlying these reductions remain unclear. We have previously shown that TNF-α plays an important role in the destruction of acinar structures. Here we examined TNF-α's function in the expression of aquaporin (AQP) 5 in human salivary gland acinar cells. Immortalized human salivary gland acinar (NS-SV-AC) cells were treated with TNF-α, and then the expression levels of AQP5 mRNA and protein were analysed. In addition, the mechanisms underlying the reduction of AQP5 expression by TNF-α treatment were investigated. TNF-α-treatment of NS-SV-AC cells significantly suppressed the expression levels of AQP5 mRNA and protein, and reduced the net fluid secretion rate. We examined the expression and activation levels of DNA methyltransferases (Dnmts) in NS-SV-AC cells treated with TNF-α. However, no significant changes were observed in the expression or activation levels of Dnmt1, Dnmt3a or Dnmt3b. Although we also investigated the role of NF-κB activity in the TNF-α-induced suppression of AQP5 expression in NS-SV-AC cells, we detected similar TNF-α suppression of AQP5 expression in non-transfected cells and in a super-repressor form of IκBα cDNA-transfected cell clones. However, interestingly, chromatin immunoprecipitation analysis demonstrated a remarkable decrease in levels of acetylated histone H4 associated with the AQP5 gene promoter after treatment with TNF-α in NS-SV-AC cells. Therefore, our results may indicate that TNF-α inhibition of AQP5 expression in human salivary gland acinar cells is due to the epigenetic mechanism by suppression of acetylation of histone H4.

  20. Reply to 'Some More Comments on Folate Deficiency in Chronic Pancreatitis'

    Directory of Open Access Journals (Sweden)

    Joan M Braganza

    2010-12-01

    Full Text Available Dear Sir, Dr Wagner’s erudite comments in the present issue of JOP. J Pancreas (Online [1] further illuminate the complex interactions between micronutrient deficiency, electrophilic stress, and disrupted methionine homeostasis, that together seem to precipitate chronic pancreatitis by impairing the exocytosis of zymogen granules from pancreatic acinar cells [2, 3]. Dr Wagner’s studies and arguments [1] underline the essentiality of methyl moieties for exocytosis. They act directly (by carboxymethylating small G proteins in the apical membrane, and indirectly by incorporation into phosphatidylcholine for granule membrane-apical membrane fusion during the exocytosis process. Dietary methionine is the main source of methyl groups, delivered via its first metabolite Sadenosylmethionine (SAM. Dietary folic acid - in concert with vitamin B12 and ascorbic acid (bioactive fraction of vitamin C - facilitates methionine regeneration from homocysteine. Dietary betaine and choline provide pre-formed methyl groups. The ancillary methyl sources (folic acid, betaine, choline could determine whether or not exocytosis can proceed when methionine intake falls short of need, as it does (along with insufficiency of vitamin C in chronic pancreatitis wherein demand increases due to cytochrome P450 induction [4], with increased release of reactive oxygen and xenobiotic species [2]. The vulnerability to the ensuing electrophilic stress of enzymes such as that which catalyses the conversion of methionine to SAM [5] rationalizes both the surge in circulating level of methionine and SAM in an acute exacerbation of chronic pancreatitis [6, 7], and evidence that the methionine metabolic pathway remains fractured thereafter [8]. A supplement of methionine (or SAM plus vitamin C curbs attacks, and additional choline (theoretically betaine alternatively [1] is helpful when treatment fails [2]. All these observations indicate the clinical relevance of methionine plus

  1. Intraductal delivery of adenoviruses targets pancreatic tumors in transgenic Ela-myc mice and orthotopic xenografts.

    Science.gov (United States)

    José, Anabel; Sobrevals, Luciano; Miguel Camacho-Sánchez, Juan; Huch, Meritxell; Andreu, Núria; Ayuso, Eduard; Navarro, Pilar; Alemany, Ramon; Fillat, Cristina

    2013-01-01

    Gene-based anticancer therapies delivered by adenoviruses are limited by the poor viral distribution into the tumor. In the current work we have explored the feasibility of targeting pancreatic tumors through a loco-regional route. We have taken advantage of the ductal network in the pancreas to retrogradelly inject adenoviruses through the common bile duct in two different mouse models of pancreatic carcinogenesis: The transgenic Ela-myc mice that develop mixed neoplasms displaying both acinar-like and duct-like neoplastic cells affecting the whole pancreas; and mice bearing PANC-1 and BxPC-3 orthotopic xenografts that constitute a model of localized human neoplastic tumors. We studied tumor targeting and the anticancer effects of newly thymidine kinase-engineered adenoviruses both in vitro and in vivo, and conducted comparative studies between intraductal or intravenous administration. Our data indicate that the intraductal delivery of adenovirus efficiently targets pancreatic tumors in the two mouse models. The in vivo application of AduPARTKT plus ganciclovir (GCV) treatment induced tumor regression in Ela-myc mice. Moreover, the intraductal injection of ICOVIR15-TKT oncolytic adenoviruses significantly improved mean survival of mice bearing PANC-1 and BxPC-3 pancreatic xenografts from 30 to 52 days and from 20 to 68 days respectively (p less than 0.0001) when combined with GCV. Of notice, both AduPARTKT and ICOVIR15-TKT antitumoral responses were stronger by ductal viral application than intravenously, in line with the 38-fold increase in pancreas transduction observed upon ductal administration. In summary our data show that cytotoxic adenoviruses retrogradelly injected to the pancreas can be a feasible approach to treat localized pancreatic tumors.

  2. Ascl3 expression marks a progenitor population of both acinar and ductal cells in mouse salivary glands.

    Science.gov (United States)

    Bullard, Tara; Koek, Laurie; Roztocil, Elisa; Kingsley, Paul D; Mirels, Lily; Ovitt, Catherine E

    2008-08-01

    Ascl3, also know as Sgn1, is a member of the mammalian achaete scute (Mash) gene family of transcription factors, which have been implicated in cell fate specification and differentiation. In the mouse salivary gland, expression of Ascl3 is restricted to a subset of duct cells. Salivary gland function depends on the secretory acinar cells, which are responsible for saliva formation, and duct cells, which modify the saliva and conduct it to the oral cavity. The salivary gland ducts are also the putative site of progenitor cells in the adult gland. Using a Cre recombinase-mediated reporter system, we followed the fate of Ascl3-expressing cells after the introduction of an EGFP-Cre expression cassette into the Ascl3 locus by homologous recombination. Lineage tracing shows that these cells are progenitors of both acinar and ductal cell types in all three major salivary glands. In the differentiated progeny, expression of Ascl3 is down-regulated. These data directly demonstrate a progenitor-progeny relationship between duct cells and the acinar cell compartment, and identify a population of multipotent progenitor cells, marked by expression of Ascl3, which is capable of generating both gland cell types. We conclude that Ascl3-expressing cells contribute to the maintenance of the adult salivary glands.

  3. [Thapsigargin-sensitive and insensitive intracellular calcium stores in acinar cells of the submandibular salivary gland in rats].

    Science.gov (United States)

    Kopach, O V; Kruhlykov, I A; Voĭtenko, N V; Fedirko, N V

    2005-01-01

    Acinar cells of rat submandibular salivary gland are characterized by heterogeneity of intracellular Ca2+ stores. In the present work we have studied this heterogeneity using Arsenazo III dye to measure a cellular total calcium content and Fura-2/AM, to determine free cytosolic calcium concentration ([Ca2+]i). We have found that the amount of Ca2+ released by inhibition of Ca2+ ATPase of the ER with thapsigargin comprises approximately 30% of total ER calcium. This result was obtained in experiments on both intact and permeabilized acinar cells. We have also shown that both Ca2+ ATPase inhibition with thapsigargin and emptying the stores with acetylcholine (ACh) led to activation of store-operated Ca2+ influx (an increase in total calcium content of approximately 14%). In permeabilized cells application of ACh after preincubation with thapsigargin led to a further decrease in total cellular calcium content (approximately 38%). At the same time in intact cells it resulted in generation of [Ca2+]i transients with gradually decreasing amplitudes. Thus, ACh is capable of producing an additional release of Ca2+ from thapsigargin-insensitive stores. This additional release is IP3-dependent since it was completely blocked by heparin. We conclude that in acinar cells of rat submandibular gland thapsigargin-sensitive and thapsigargin-insensitive Ca2+ stores could exist.

  4. Pancreatic encephalopathy- a rare complication of severe acute biliary pancreatitis

    OpenAIRE

    Vlad Denis Constantin; Alexandru Carȃp; Bogdan Socea; Simona Bobic

    2014-01-01

    Background. Pancreatic encephalopathy is a rare complication of severe acute pancreatitis, with high mortality, being difficult to diagnose and treat, thus requiring continuous research regarding its management. Materials and Methods. Of 20 patients diagnosed with severe acute pancreatitis on admission at Department of Emergency and Admission (DEA), from January 1st 2010 to March 31st 2014, 5 cases complicated by pancreatic encephalopathy were analyzed using a descriptive observational...

  5. Pancreatic tissue fluid pressure during drainage operations for chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Madsen, P;

    1990-01-01

    Pancreatic tissue fluid pressure was measured in 10 patients undergoing drainage operations for painful chronic pancreatitis. The pressure was measured by the needle technique in the three anatomic regions of the pancreas before and at different stages of the drainage procedure, and the results...... a decrease in pancreatic tissue fluid pressure during drainage operations for pain in chronic pancreatitis. Regional pressure decrease were apparently unrelated to ERCP findings....

  6. Endoscopic pancreatic duct stent placement for inflammatory pancreatic diseases

    OpenAIRE

    Testoni, Pier Alberto

    2007-01-01

    The role of endoscopic therapy in the management of pancreatic diseases is continuously evolving; at present most pathological conditions of the pancreas are successfully treated by endoscopic retrograde cholangio-pancreatography (ERCP) or endoscopic ultrasound (EUS), or both. Endoscopic placement of stents has played and still plays a major role in the treatment of chronic pancreatitis, pseudocysts, pancreas divisum, main pancreatic duct injuries, pancreatic fistulae, complications of acute ...

  7. Hereditary pancreatitis and secondary screening for early pancreatic cancer.

    Science.gov (United States)

    Vitone, L J; Greenhalf, W; Howes, N R; Neoptolemos, J P

    2005-01-01

    Hereditary pancreatitis is an autosomal dominant disease with incomplete penetrance (80%), accounting for approximately 1% of all cases of pancreatitis. It is characterized by the onset of recurrent attacks of acute pancreatitis in childhood and frequent progression to chronic pancreatitis. Whitcomb et al. identified the cationic trypsinogen gene (PRSS1) on chromosome 7q35 as the site of the mutation that causes hereditary pancreatitis. The European registry of hereditary pancreatitis and familial pancreatic cancer (EUROPAC) aims to identify and make provisions for those affected by hereditary pancreatitis and familial pancreatic cancer. The most common mutations in hereditary pancreatitis are R122H, N29I and A16V but many families have been described with clinically defined hereditary pancreatitis where there is no PRSS1 mutation. It is known that the cumulative lifetime risk (to age 70 years) of pancreatic cancer is 40% in individuals with hereditary pancreatitis. This subset of individuals form an ideal group for the development of a screening programme aimed at detecting pancreatic cancer at an early stage in an attempt to improve the presently poor long-term survival. Current screening strategies involve multimodality imaging (computed tomography, endoluminal ultrasound) and endoscopic retrograde cholangiopancreatography for pancreatic juice collection followed by molecular analysis of the DNA extracted from the juice. The potential benefit of screening (curative resection) must be balanced against the associated morbidity and mortality of surgery. Philosophically, the individual's best interest must be sought in light of the latest advances in medicine and science following discussions with a multidisciplinary team in specialist pancreatic centres.

  8. Ablation of sensory neurons in a genetic model of pancreatic ductal adenocarcinoma slows initiation and progression of cancer.

    Science.gov (United States)

    Saloman, Jami L; Albers, Kathryn M; Li, Dongjun; Hartman, Douglas J; Crawford, Howard C; Muha, Emily A; Rhim, Andrew D; Davis, Brian M

    2016-03-15

    Pancreatic ductal adenocarcinoma (PDAC) is characterized by an exuberant inflammatory desmoplastic response. The PDAC microenvironment is complex, containing both pro- and antitumorigenic elements, and remains to be fully characterized. Here, we show that sensory neurons, an under-studied cohort of the pancreas tumor stroma, play a significant role in the initiation and progression of the early stages of PDAC. Using a well-established autochthonous model of PDAC (PKC), we show that inflammation and neuronal damage in the peripheral and central nervous system (CNS) occurs as early as the pancreatic intraepithelial neoplasia (PanIN) 2 stage. Also at the PanIN2 stage, pancreas acinar-derived cells frequently invade along sensory neurons into the spinal cord and migrate caudally to the lower thoracic and upper lumbar regions. Sensory neuron ablation by neonatal capsaicin injection prevented perineural invasion (PNI), astrocyte activation, and neuronal damage, suggesting that sensory neurons convey inflammatory signals from Kras-induced pancreatic neoplasia to the CNS. Neuron ablation in PKC mice also significantly delayed PanIN formation and ultimately prolonged survival compared with vehicle-treated controls (median survival, 7.8 vs. 4.5 mo; P = 0.001). These data establish a reciprocal signaling loop between the pancreas and nervous system, including the CNS, that supports inflammation associated with oncogenic Kras-induced neoplasia. Thus, pancreatic sensory neurons comprise an important stromal cell population that supports the initiation and progression of PDAC and may represent a potential target for prevention in high-risk populations.

  9. Nitric oxide signals are interlinked with calcium signals in normal pancreatic stellate cells upon oxidative stress and inflammation

    Science.gov (United States)

    2016-01-01

    The mammalian diffuse stellate cell system comprises retinoid-storing cells capable of remarkable transformations from a quiescent to an activated myofibroblast-like phenotype. Activated pancreatic stellate cells (PSCs) attract attention owing to the pivotal role they play in development of tissue fibrosis in chronic pancreatitis and pancreatic cancer. However, little is known about the actual role of PSCs in the normal pancreas. These enigmatic cells have recently been shown to respond to physiological stimuli in a manner that is markedly different from their neighbouring pancreatic acinar cells (PACs). Here, we demonstrate the capacity of PSCs to generate nitric oxide (NO), a free radical messenger mediating, for example, inflammation and vasodilatation. We show that production of cytosolic NO in PSCs is unambiguously related to cytosolic Ca2+ signals. Only stimuli that evoke Ca2+ signals in the PSCs elicit consequent NO generation. We provide fresh evidence for the striking difference between signalling pathways in PSCs and adjacent PACs, because PSCs, in contrast to PACs, generate substantial Ca2+-mediated and NOS-dependent NO signals. We also show that inhibition of NO generation protects both PSCs and PACs from necrosis. Our results highlight the interplay between Ca2+ and NO signalling pathways in cell–cell communication, and also identify a potential therapeutic target for anti-inflammatory therapies. PMID:27488376

  10. Extended exenatide administration enhances lipid metabolism and exacerbates pancreatic injury in mice on a high fat, high carbohydrate diet.

    Directory of Open Access Journals (Sweden)

    Rodney Rouse

    Full Text Available This study expanded upon a previous study in mice reporting a link between exenatide treatment and exocrine pancreatic injury by demonstrating temporal and dose responses and providing an initial mechanistic hypothesis. The design of the present study included varying lengths of exenatide exposure (3, 6 weeks to 12 weeks at multiple concentrations (3, 10, or 30 µg/kg with multiple endpoints (histopathology evaluations, immunoassay for cytokines, immunostaining of the pancreas, serum chemistries and measurement of trypsin, amylase, and, lipase, and gene expression profiles. Time- and dose-dependent exocrine pancreatic injury was observed in mice on a high fat diet treated with exenatide. The morphological changes identified in the pancreas involved acinar cell injury and death (autophagy, apoptosis, necrosis, and atrophy, cell adaptations (hypertrophy and hyperplasia, and cell survival (proliferation/regeneration accompanied by varying degrees of inflammatory response leading to secondary injury in pancreatic blood vessels, ducts, and adipose tissues. Gene expression profiles indicated increased signaling for cell survival and altered lipid metabolism in exenatide treated mice. Immunohistochemistry supported gene expression findings that exenatide caused and/or exacerbated pancreatic injury in a high fat diet environment potentially by further increasing high fat diet exacerbated lipid metabolism and resulting oxidative stress. Further investigation is required to confirm these findings and determine their relevance to human disease.

  11. Type 1 autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Zen Yoh

    2011-12-01

    Full Text Available Abstract Before the concept of autoimmune pancreatitis (AIP was established, this form of pancreatitis had been recognized as lymphoplasmacytic sclerosing pancreatitis or non-alcoholic duct destructive chronic pancreatitis based on unique histological features. With the discovery in 2001 that serum IgG4 concentrations are specifically elevated in AIP patients, this emerging entity has been more widely accepted. Classical cases of AIP are now called type 1 as another distinct subtype (type 2 AIP has been identified. Type 1 AIP, which accounts for 2% of chronic pancreatitis cases, predominantly affects adult males. Patients usually present with obstructive jaundice due to enlargement of the pancreatic head or thickening of the lower bile duct wall. Pancreatic cancer is the leading differential diagnosis for which serological, imaging, and histological examinations need to be considered. Serologically, an elevated level of IgG4 is the most sensitive and specific finding. Imaging features include irregular narrowing of the pancreatic duct, diffuse or focal enlargement of the pancreas, a peri-pancreatic capsule-like rim, and enhancement at the late phase of contrast-enhanced images. Biopsy or surgical specimens show diffuse lymphoplasmacytic infiltration containing many IgG4+ plasma cells, storiform fibrosis, and obliterative phlebitis. A dramatic response to steroid therapy is another characteristic, and serological or radiological effects are normally identified within the first 2 or 3 weeks. Type 1 AIP is estimated as a pancreatic manifestation of systemic IgG4-related disease based on the fact that synchronous or metachronous lesions can develop in multiple organs (e.g. bile duct, salivary/lacrimal glands, retroperitoneum, artery, lung, and kidney and those lesions are histologically identical irrespective of the organ of origin. Several potential autoantigens have been identified so far. A Th2-dominant immune reaction and the activation of

  12. Pancreatic ductal system obstruction and acute recurrent pancreatitis

    Institute of Scientific and Technical Information of China (English)

    M Delhaye; C Matos; M Arvanitakis; J Devière

    2008-01-01

    Acute recurrent pancreatitis is a clinical entity largely associated with pancreatic ductal obstruction.This latter includes congenital variants,of which pancreas divisum is the most frequent but also controversial,chronic pancreatitis,tumors of the pancreaticobiliary junction and sphincter of Oddi dysfunction.This review summarizes current knowledge about diagnostic work-up and therapy of these conditions.

  13. Clinical pancreatic disorder I: Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Åke Andrén-Sandberg

    2011-01-01

    Now the pancreatic abstracts of American Pancreas Club 2011 are gathered and filed with the aim to give them a larger audience than they have had in their original abstract book. However, it is obvious that most of clinical fellows do not have time to read all the abstracts. For them I have made a "clinical highlight section" of 10 percent of all the pancreatic abstracts. If someone else should have done some collection of abstract, there should probably have been other selections, but as this is not the case, the editor′s choices are the highlighted ones. The article as series I of clinical highlight section is present, and more series will be present in the following issues. If readers will remember some of the abstracts better after reading this "abstract of abstracts", it was worth the efforts - and without efforts there will be little progress.

  14. Pain in chronic pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Fasanella, Kenneth E; Davis, Brian; Lyons, John; Chen, Zongfu; Lee, Kenneth K; Slivka, Adam; Whitcomb, David C

    2007-06-01

    Chronic, debilitating abdominal pain is arguably the most important component of chronic pancreatitis, leading to significant morbidity and disability. Attempting to treat this pain, which is too often unsuccessful, is a frustrating experience for physician and patient. Multiple studies to improve understanding of the pathophysiology that causes pain in some patients but not in others have been performed since the most recent reviews on this topic. In addition, new treatment modalities have been developed and evaluated in this population. This review discusses new advances in neuroscience and the study of visceral pain mechanisms, as well as genetic factors that may play a role. Updates of established therapies, as well as new techniques used in addressing pain from chronic pancreatitis, are reviewed. Lastly, outcome measures, which have been highly variable in this field over the years, are addressed. PMID:17533083

  15. Endoscopic treatment of chronic pancreatitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Treatment of chronic pancreatitis has been exclusively surgical for a long time. Recently, endoscopic therapy has become widely used as a primary therapeutic option.Initially performed for drainage of pancreatic cysts and pseudocysts, endoscopic treatments were adapted to biliary and pancreatic ducts stenosis. Pancreatic sphincterotomy which allows access to pancreatic ducts was firstly reported. Secondly, endoscopic methods of stenting, dilatation, and stones extraction of the bile ducts were applied to pancreatic ducts. Nevertheless,new improvements were necessary: failures of pancreatic stone extraction justified the development of extra-corporeal shock wave lithotripsy; dilatation of pancreatic stenosis was improved by forage with a new device; moreover endosonography allowed guidance for celiac block, gastro-cystostomy, duodeno-cystostomy and pancreatico-gastrostomy. Although endoscopic treatments are more and more frequently accepted,indications are still debated.

  16. Loperamide-Induced Acute Pancreatitis

    OpenAIRE

    Halla Vidarsdottir; Hanna Vidarsdottir; Pall Helgi Moller; Einar Stefan Bjornsson

    2013-01-01

    Acute pancreatitis is a common disease leading to hospitalizations, most often caused by gallstones or alcohol. We present a case of a patient diagnosed with acute pancreatitis considered to be due to loperamide treatment for diarrhea.

  17. Drugs Approved for Pancreatic Cancer

    Science.gov (United States)

    ... Ask about Your Treatment Research Drugs Approved for Pancreatic Cancer This page lists cancer drugs approved by the ... that are not listed here. Drugs Approved for Pancreatic Cancer Abraxane (Paclitaxel Albumin-stabilized Nanoparticle Formulation) Afinitor (Everolimus) ...

  18. [The epidemiology of pancreatic cancer].

    Science.gov (United States)

    Lakatos, Gábor; Tulassay, Zsolt

    2010-10-31

    Pancreatic cancer is a relatively uncommon tumor, but even with early diagnosis, mortality rates are high, explaining why this form of cancer has now become a common cause of cancer mortality. There are no screening tests for early detection of pancreatic cancer. It is more common in men than women and is predominantly a disease of elderly people. There is wide variation in the incidence of pancreatic cancer around the world, suggesting that environmental factors are important in the pathogenesis. Smoking is the major known risk factor for pancreatic cancer, while dietary factors seem to be less important. Other possible risk factors include chronic pancreatitis, obesity and type 2 diabetes. Numerous inherited germ line mutations are associated with pancreatic cancer. Of these, hereditary pancreatitis confers the greatest risk, while BRCA2 mutations are the commonest inherited disorder. Polymorphisms in genes that control detoxification of environmental carcinogens and metabolic pathways may alter the risk of pancreatic cancer.

  19. Genetics Home Reference: hereditary pancreatitis

    Science.gov (United States)

    ... National Cancer Institute: Pancreatic Cancer National Institute of Diabetes and Digestive and Kidney Diseases Educational Resources (9 links) Boston Children's Hospital Cleveland Clinic: Cancer of the Pancreas Cleveland Clinic: Pancreatitis Disease InfoSearch: ...

  20. Drug-induced acute pancreatitis

    OpenAIRE

    Eland, I.A.

    2008-01-01

    textabstractAcute pancreatitis is an inflammatory disease of the pancreas with sudden onset. The severity of acute pancreatitis may vary from mild to life threatening. There are many risk factors for acute pancreatitis, among which gallstones and alcohol abuse are most widely known. Drugs are considered as potential risk factors for acute pancreatitis, but have received relatively little attention in the medical literature. In this thesis, several epidemiological studies were performed to ass...

  1. Concurrent Lymphoma and Pancreatic Adenocarcinoma

    OpenAIRE

    Jiun Miin Lai; Mehrdad Nikfarjam; Peter Crowley

    2011-01-01

    Context Retroperitoneal lymph node enlargement in patients with pancreatic cancer is sometimes treated as incurable disease. Nonmetastatic causes of lymphadenopathy should however be considered. Case reports Two cases of significant retroperitoneal lymphadenopathy in the setting of pancreatic cancer, treated by pancreaticoduodenectomy and lymph node dissection are described. Both cases had a final diagnosis of concurrent pancreatic cancer and lymphoma with no evidence of pancreatic lymph node...

  2. Folate Deficiency in Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Gopalakrishna Rajesh

    2010-07-01

    Full Text Available Dear Sir, While there has been a spurt of interest in genetic alterations associated with pancreatitis in the past few years, interest in the role of environmental factors has largely focused on alcoholism and smoking with insufficient attention being paid to the contributions of nutritional deficiency, and the role of environmental toxins in the pathogenesis of pancreatitis. Braganza and Dormandy [1] argue convincingly about the role played by cytochrome P450 monooxygenases (especially CYP1A enzyme induction by xenobiotics and the resultant oxidative stress, as also the now increasingly recognized reductive stress posed by the metabolites in initiating pancreatic injury. Their article underlines the important part played by the deficiency of methyl and thiol molecules in different stages of the progression of pancreatic damage. Furthermore, they attempt to establish a link between environmental and genetic factors and bring in a holistic view on the etiopathogenesis of chronic pancreatitis. We have recently demonstrated lower plasma methionine levels in two cohorts of chronic pancreatitis patients; one of tropical chronic pancreatitis and the other, of alcoholic chronic pancreatitis as compared to healthy controls [2] which suggests that deficiency of methyl groups may be a factor in various forms of pancreatitis. Similarly, we have shown lower red cell glutathione levels in chronic pancreatitis patients with tropical chronic pancreatitis and alcoholic chronic pancreatitis, indicating deficiency of thiol molecules. In addition, we have demonstrated significantly higher levels of plasma total homocysteine in chronic pancreatitis patients than in healthy controls. Moreover, our study has shown that there is a deficiency of red cell folate in the majority of chronic pancreatitis patients, more so in tropical chronic pancreatitis; and that folate deficiency appeared to be the key factor in hyperhomocysteinemia in chronic pancreatitis patients

  3. Obstructive Jaundice in Chronic Pancreatitis

    OpenAIRE

    Hollands, M. J.; Little, J. M.

    1989-01-01

    Significant obstructive jaundice in chronic pancreatitis is generally considered to be rare. Eleven of 57 consecutive patients with proven chronic pancreatitis have developed significant obstructive jaundice of more than transient duration. Eight presented as jaundice complicating known pancreatitis and three as jaundice of unknown cause. Life table analysis showed a steady rise in the risk of developing jaundice up to the end of 10 years from the onset of chronic pancreatitis. Jaundice was f...

  4. Genetic basis of chronic pancreatitis

    NARCIS (Netherlands)

    Jansen, JBMJ; Morsche, RT; van Goor, Harry; Drenth, JPH

    2002-01-01

    Background: Pancreatitis has a proven genetic basis in a minority of patients. Methods: Review of the literature on genetics of pancreatitis. Results: Ever since the discovery that in most patients with hereditary pancreatitis a mutation in the gene encoding for cationic trypsinogen (R122H) was foun

  5. Drug-induced acute pancreatitis

    NARCIS (Netherlands)

    I.A. Eland

    2003-01-01

    textabstractAcute pancreatitis is an inflammatory disease of the pancreas with sudden onset. The severity of acute pancreatitis may vary from mild to life threatening. There are many risk factors for acute pancreatitis, among which gallstones and alcohol abuse are most widely known. Drugs are consid

  6. Acute pancreatitis and Cushing's syndrome.

    OpenAIRE

    Clague, H W; B. Warren; Krasner, N.

    1984-01-01

    A case of acute necrotizing pancreatitis in a 53-year-old man with an ectopic adrenocorticotrophin (ACTH) producing bronchial carcinoma is described. The aetiology of acute pancreatitis in relation to steroid therapy and malignancy is discussed and it is suggested that excess endogenous steroid production may also cause acute pancreatitis.

  7. Prognostic Factors in Pancreatic Cancer

    OpenAIRE

    Åke Andrén-Sandberg

    2012-01-01

    Prognostic factors in pancreatic cancer have been a hot topic for the clinical pancreatology, and many studies have been involved in the field. The author reviewed the pancreatic abstracts of American Pancreas Club 2011, and sumarized "highlight" of all the abstracts in prognostic factors in pancreatic cancer.

  8. Familial pancreatic cancer: genetic advances

    OpenAIRE

    Rustgi, Anil K.

    2014-01-01

    This review by Rustgi elaborates on the known genetic syndromes that underlie familial pancreatic cancer. It aims to delineate the subtypes of syndromic hereditary pancreatic cancer in which germline genetic mutations have been identified and nonsyndromic familial pancreatic cancer in which genetic information is emerging.

  9. Treatment Option Overview (Pancreatic Cancer)

    Science.gov (United States)

    ... affect prognosis (chance of recovery) and treatment options. Pancreatic cancer is a disease in which malignant (cancer) cells form in the ... the cancer cells in the liver are actually pancreatic cancer cells. The disease is metastatic pancreatic cancer, not liver cancer. The ...

  10. General Information about Pancreatic Cancer

    Science.gov (United States)

    ... affect prognosis (chance of recovery) and treatment options. Pancreatic cancer is a disease in which malignant (cancer) cells form in the ... the cancer cells in the liver are actually pancreatic cancer cells. The disease is metastatic pancreatic cancer, not liver cancer. The ...

  11. DOG1: a novel marker of salivary acinar and intercalated duct differentiation.

    Science.gov (United States)

    Chênevert, Jacinthe; Duvvuri, Umamaheswar; Chiosea, Simion; Dacic, Sanja; Cieply, Kathleen; Kim, Jean; Shiwarski, Daniel; Seethala, Raja R

    2012-07-01

    Anoctamin-1 (ANO1) (DOG1, TMEM16a) is a calcium-activated chloride channel initially described in gastrointestinal stromal tumors, but now known to be expressed in a variety of normal and tumor tissues including salivary tissue in murine models. We herein perform a comprehensive survey of DOG1 expression in 156 cases containing non-neoplastic human salivary tissues and tumors. ANO1 mRNA levels were significantly higher (8-fold increase, Pcells, striated and excretory ducts were invariably negative. All acinic cell carcinomas (n=28) were DOG1 positive demonstrating a complex mixture of intense (3+) apical membranous, cytoplasmic and complete membranous staining. Most ductal tumor types were negative or only showed a subset of positive cases. Within the biphasic tumor category, adenoid cystic carcinomas (18/24 cases) and epithelial-myoepithelial carcinomas (8/15 cases) were frequently positive, often showing a distinctive combined apical ductal and membranous/cytoplasmic myoepithelial staining profile. Thus, DOG1 staining is a marker of salivary acinar and to a lesser extent intercalated duct differentiation. Strong staining can be used to support the diagnosis of acinic cell carcinoma. DOG1 may also be a marker of a 'transformed' myoepithelial phenotype in a subset of biphasic salivary gland malignancies.

  12. Antigen-presenting cells in parotid glands contain cystatin D originating from acinar cells.

    Science.gov (United States)

    Nashida, Tomoko; Sato, Ritsuko; Haga-Tsujimura, Maiko; Yoshie, Sumio; Yoshimura, Ken; Imai, Akane; Shimomura, Hiromi

    2013-02-01

    Cystatin D encoded by Cst5 is a salivary classified type II cystatin. We investigated the dynamism of cystatin D by examining the distribution of cystatin D protein and mRNA in rats, to identify novel functions. The simultaneous expression of Cst5 and cystatin D was observed in parotid glands, however in situ hybridization showed that only acinar cells produced cystatin D. Synthesized cystatin D was localized in small vesicles and secreted from the apical side to the saliva, and from the basolateral side to the extracellular region, a second secretory pathway for cystatin D. We also identified antigen-presenting cells in the parotid glands that contained cystatin D without the expression of Cst5, indicating the uptake of cystatin D from the extracellular region. Cystatin D was detected in blood serum and renal tubular cells with megalin, indicating the circulation of cystatin D through the body and uptake by renal tubular cells. Thus, the novel dynamism of cystatin D was shown and a function for cystatin D in the regulation of antigen-presenting cell activity was proposed.

  13. Clinical pancreatic disorder I: Acute pancreatitis.

    Science.gov (United States)

    Andrén-Sandberg, Ake

    2011-07-01

    The Annual American Pancreas Club is an important event for communicating around clinical pancreatic disorders, just as the European, Japanese, Indian, and the International Pancreatic association. Even though the meeting is only 1½ day there were 169 different abstracts and a "How do I do it session." Among all these abstracts on the pancreas there are some real pearls, but they are almost always well hidden, never highlighted - all abstracts are similarly presented - and will too soon be forgotten. The present filing of the abstracts is one way (not the way) to get the pancreatic abstracts a little more read and a little more remembered - and perhaps a little more cited. It should also be understood that most of the abstracts are short summaries of hundreds of working hours (evenings, nights, weekends, holidays, you name them …) in the laboratory or in the clinic, often combined with blood, sweat and tears. The authors should be shown at least some respect, and their abstracts should not only be thought of as "just another little abstract" - and the best respect they can be shown are that they will be remembered to be another brick in our scientific wall.Now the pancreatic abstracts of American Pancreas Club 2011 are gathered and filed with the aim to give them a larger audience than they have had in their original abstract book. However, it is obvious that most of clinical fellows do not have time to read all the abstracts. For them I have made a "clinical highlight section" of 10 percent of all the pancreatic abstracts. If someone else should have done some collection of abstract, there should probably have been other selections, but as this is not the case, the editor's choices are the highlighted ones.The article as series I of clinical highlight section is present, and more series will be present in the following issues. If readers will remember some of the abstracts better after reading this "abstract of abstracts", it was worth the efforts - and without

  14. Clinical pancreatic disorder I: Acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Åke Andrén-Sandberg

    2011-07-01

    Full Text Available The Annual American Pancreas Club is an important event for communicating around clinical pancreatic disorders, just as the European, Japanese, Indian, and the International Pancreatic association. Even though the meeting is only 1½ day there were 169 different abstracts and a “How do I do it session.” Among all these abstracts on the pancreas there are some real pearls, but they are almost always well hidden, never highlighted – all abstracts are similarly presented – and will too soon be forgotten. The present filing of the abstracts is one way (not the way to get the pancreatic abstracts a little more read and a little more remembered – and perhaps a little more cited. It should also be understood that most of the abstracts are short summaries of hundreds of working hours (evenings, nights, weekends, holidays, you name them … in the laboratory or in the clinic, often combined with blood, sweat and tears. The authors should be shown at least some respect, and their abstracts should not only be thought of as “just another little abstract” – and the best respect they can be shown are that they will be remembered to be another brick in our scientific wall.Now the pancreatic abstracts of American Pancreas Club 2011 are gathered and filed with the aim to give them a larger audience than they have had in their original abstract book. However, it is obvious that most of clinical fellows do not have time to read all the abstracts. For them I have made a “clinical highlight section” of 10 percent of all the pancreatic abstracts. If someone else should have done some collection of abstract, there should probably have been other selections, but as this is not the case, the editor’s choices are the highlighted ones. The article as series I of clinical highlight section is present, and more series will be present in the following issues. If readers will remember some of the abstracts better after reading this “abstract of

  15. Tests of pancreatic exocrine function - clinical significance in pancreatic and non-pancreatic disorders.

    Science.gov (United States)

    Keller, Jutta; Aghdassi, Ali Alexander; Lerch, Markus M; Mayerle, Julia V; Layer, Peter

    2009-01-01

    The pancreas functions as the main factory for digestive enzymes and therefore enables food utilisation. Pancreatic exocrine insufficiency, partial or complete loss of digestive enzyme synthesis, occurs primarily in disorders directly affecting pancreatic tissue integrity. However, other disorders of the gastrointestinal tract, such as coeliac disease, inflammatory bowel disease, Zollinger-Ellison syndrome or gastric resection can either mimic or cause pancreatic exocrine insufficiency. The overt clinical symptoms of pancreatic exocrine insufficiency are steatorrhoea and maldigestion, which frequently become apparent in advanced stages. Several direct and indirect function tests are available for assessment of pancreatic function but until today diagnosis of excretory insufficiency is difficult as in mild impairment clinically available function tests show limitations of diagnostic accuracy. This review focuses on diagnosis of pancreatic exocrine insufficiency in pancreatic and non-pancreatic disorders. PMID:19505669

  16. Autoantibodies in chronic pancreatitis

    DEFF Research Database (Denmark)

    Rumessen, J J; Marner, B; Pedersen, N T;

    1985-01-01

    In 60 consecutive patients clinically suspected of having chronic pancreatitis the serum concentration of the immunoglobulins (IgA, IgG, IgM), the IgG- and IgA-type non-organ-specific autoantibodies against nuclear material (ANA), smooth and striated muscle, mitochondria, basal membrane, and reti......In 60 consecutive patients clinically suspected of having chronic pancreatitis the serum concentration of the immunoglobulins (IgA, IgG, IgM), the IgG- and IgA-type non-organ-specific autoantibodies against nuclear material (ANA), smooth and striated muscle, mitochondria, basal membrane......, and reticulin, and the IgG- and IgA-type pancreas-specific antibodies against islet cells, acinus cells, and ductal cells (DA) were estimated blindly. In 23 of the patients chronic pancreatitis was verified, whereas chronic pancreatitis was rejected in 37 patients (control group). IgG and IgA were found...... in significantly higher concentrations in the patients with chronic pancreatitis than in the control group but within the normal range. ANA and DA occurred very frequently in both groups but with no statistical difference. Other autoantibodies only occurred sporadically. The findings of this study do not support...

  17. Hepatobiliary and pancreatic ascariasis

    Science.gov (United States)

    Khuroo, Mohammad S; Rather, Ajaz A; Khuroo, Naira S; Khuroo, Mehnaaz S

    2016-01-01

    Hepatobiliary and pancreatic ascariasis (HPA) was described as a clinical entity from Kashmir, India in 1985. HPA is caused by invasion and migration of nematode, Ascaris lumbricoides, in to the biliary tract and pancreatic duct. Patients present with biliary colic, cholangitis, cholecystitis, hepatic abscesses and acute pancreatitis. Ascarides traverse the ducts repeatedly, get trapped and die, leading to formation of hepatolithiasis. HPA is ubiquitous in endemic regions and in Kashmir, one such region, HPA is the etiological factor for 36.7%, 23%, 14.5% and 12.5% of all biliary diseases, acute pancreatitis, liver abscesses and biliary lithiasis respectively. Ultrasonography is an excellent diagnostic tool in visualizing worms in gut lumen and ductal system. The rational treatment for HPA is to give appropriate treatment for clinical syndromes along with effective anthelmintic therapy. Endotherapy in HPA is indicated if patients continue to have symptoms on medical therapy or when worms do not move out of ductal lumen by 3 wk or die within the ducts. The worms can be removed from the ductal system in most of the patients and such patients get regression of symptoms of hepatobiliary and pancreatic disease. PMID:27672273

  18. The clinical assessment of intraductal ultrasonography in the differential diagnosis of pancreatic carcinoma and chronic pancreatitis.

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    Objective: To assess and compare the clinical value of intraductal ultrasonography (IDUS) in the differential diagnosis of pancreatic carcinoma and chronic pancreatitis with conventional imaging methods. Methods: IDUS was carried out in eighteen patients with pancreatic carcinoma and chronic pancreatitis

  19. TNF-like weak inducer of apoptosis (TWEAK promotes beta cell neogenesis from pancreatic ductal epithelium in adult mice.

    Directory of Open Access Journals (Sweden)

    Fei Wu

    Full Text Available AIM/HYPOTHESIS: The adult mammalian pancreas has limited ability to regenerate in order to restore adequate insulin production from multipotent progenitors, the identity and function of which remain poorly understood. Here we test whether the TNF family member TWEAK (TNF-like weak inducer of apoptosis promotes β-cell neogenesis from proliferating pancreatic ductal epithelium in adult mice. METHODS: C57Bl/6J mice were treated with Fc-TWEAK and pancreas harvested at different time points for analysis by histology and immunohistochemistry. For lineage tracing, 4 week old double transgenic mice CAII-CreER(TM: R26R-eYFP were implanted with tamoxifen pellet, injected with Fc-TWEAK or control Ig twice weekly and analyzed at day 18 for TWEAK-induced duct cell progeny by costaining for insulin and YFP. The effect of TWEAK on pancreatic regeneration was determined by pancytokeratin immunostaining of paraffin embedded sections from wildtype and TWEAK receptor (Fn14 deficient mice after Px. RESULTS: TWEAK stimulates proliferation of ductal epithelial cells through its receptor Fn14, while it has no mitogenic effect on pancreatic α- or β-cells or acinar cells. Importantly, TWEAK induces transient expression of endogenous Ngn3, a master regulator of endocrine cell development, and induces focal ductal structures with characteristics of regeneration foci. In addition, we identify by lineage tracing TWEAK-induced pancreatic β-cells derived from pancreatic duct epithelial cells. Conversely, we show that Fn14 deficiency delays formation of regenerating foci after Px and limits their expansion. CONCLUSIONS/INTERPRETATION: We conclude that TWEAK is a novel factor mediating pancreatic β-cell neogenesis from ductal epithelium in normal adult mice.

  20. Primary Pancreatic Head Tuberculosis: Great Masquerader of Pancreatic Adenocarcinoma

    Science.gov (United States)

    Gupta, Dhaval; Patel, Jatin; Rathi, Chetan; Ingle, Meghraj; Sawant, Prabha

    2015-01-01

    Isolated pancreatic tuberculosis (TB) is considered an extremely rare condition, even in the developing countries. Most reported cases of pancreatic TB are diagnosed after exploratory laparotomy or autopsy. Pancreatic TB is a potential mimic of invasive pancreatic malignancy and the presence of vascular invasion does not distinguish one condition from the other. Every effort should be made for the earliest diagnosis of this condition as TB is a treatable condition and it avoids unnecessary management of pancreatic carcinoma. Here we report a rare case of primary pancreatic head TB in a 58-year-old male who presented with hypodense lesion in head of pancreas with double duct sign and portal vein invasion mimicking non-resectable pancreatic carcinoma.

  1. Pancreatic metastasis from mycosis fungoides mimicking primary pancreatic tumor.

    Science.gov (United States)

    Ceriolo, Paola; Fausti, Valentina; Cinotti, Elisa; Bonadio, Silvia; Raffaghello, Lizzia; Bianchi, Giovanna; Orcioni, Giulio Fraternali; Fiocca, Roberto; Rongioletti, Franco; Pistoia, Vito; Borgonovo, Giacomo

    2016-03-28

    Mycosis fungoides (MF) is a cutaneous T-cell lymphoma that can undergo local progression with possible systemic dissemination. We report a case of a patient affected by MF with a pancreatic mass that was a diagnostic challenge between primitive tumor and pancreatic metastasis from MF. Clinical setting findings and imaging studies raised the suspicion of a pancreatic primary neoplasm. A diagnostic clue was provided by the combined histomorphologic/immunohistochemical study of pancreatic and cutaneous biopsies, which revealed a pancreatic localization of MF. Considering the rarity of metastatic localization of MF to the pancreas, we next investigated whether chemokine-chemokine receptor interactions could be involved in the phenomenon to provide new insight into the possible mechanisms underlying metastatic localization of MF to the pancreas. Histological analyses of archival pancreatic tissue demonstrated that glucagon-secreting cells of the pancreatic islets expressed the CCL27 chemokine, which may have attracted in our case metastatic MF cells expressing the complementary receptor CCR10.

  2. Organellar proteomics: analysis of pancreatic zymogen granule membranes.

    Science.gov (United States)

    Chen, Xuequn; Walker, Angela K; Strahler, John R; Simon, Eric S; Tomanicek-Volk, Sarah L; Nelson, Bradley B; Hurley, Mary C; Ernst, Stephen A; Williams, John A; Andrews, Philip C

    2006-02-01

    The zymogen granule (ZG) is the specialized organelle in pancreatic acinar cells for digestive enzyme storage and regulated secretion and has been a model for studying secretory granule functions. In an initial effort to comprehensively understand the functions of this organelle, we conducted a proteomic study to identify proteins from highly purified ZG membranes. By combining two-dimensional gel electrophoresis and two-dimensional LC with tandem mass spectrometry, 101 proteins were identified from purified ZG membranes including 28 known ZG proteins and 73 previously unknown proteins, including SNAP29, Rab27B, Rab11A, Rab6, Rap1, and myosin Vc. Moreover several hypothetical proteins were identified that represent potential novel proteins. The ZG localization of nine of these proteins was further confirmed by immunocytochemistry. To distinguish intrinsic membrane proteins from soluble and peripheral membrane proteins, a quantitative proteomic strategy was used to measure the enrichment of intrinsic membrane proteins through the purification process. The iTRAQ ratios correlated well with known or Transmembrane Hidden Markov Model-predicted soluble or membrane proteins. By combining subcellular fractionation with high resolution separation and comprehensive identification of proteins, we have begun to elucidate zymogen granule functions through proteomic and subsequent functional analysis of its membrane components.

  3. Elderly Patients with Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Andromachi S Kougioumtzopoulou

    2014-07-01

    Full Text Available Pancreatic cancer marked significant increase of incidence during the last decades in the elderly population. Despite the certain increase of incidence there are no international guidelines for elderly patients who are suffering from pancreatic cancer. During the ASCO Annual Meeting 2014, two abstracts focusing on elderly patients suffering from different histological types of pancreatic cancer were presented. The first retrospective study (Abstract # 4119 showed the benefit of the systemic treatment on overall survival for elderly patients with stage IV pancreatic adenocarcinoma. The second retrospective study (Abstract # 4112 demonstrates the positive effect of somatostatin analogue (octreotide-LAR treatment on overall survival for elderly patients with neuroendocrine pancreatic carcinoma.

  4. Controlled clinical study on pancreatic stenting in the relief of pain of advanced pancreatic cancer with dilated pancreatic duct

    Institute of Scientific and Technical Information of China (English)

    高飞

    2014-01-01

    Objective To explore the efficacy of pancreatic stenting in the relief of abdominal pain of advanced pancreatic cancer with dilated pancreatic duct.Methods A tolal of 61 patients with advanced pancreatic carcinoma companied with dilated pancreatic duct were divided into two groups.Twenty-eight cases(two cases were excluded because of stent loss)in stent group treated with

  5. Post-partum pancreatitis.

    Directory of Open Access Journals (Sweden)

    Pai P

    1993-04-01

    Full Text Available Acute pancreatitis in pregnancy and post-partum period, rarely encountered in surgical practice, can have a lethal effect on the mother and the foetus. We report here a case of a 35 year old tertigravida who presented with high grade fever, abdominal pain with distension, tachycardia and tachypnoea. Chest examination and X-rays were suggestive of pneumonia. The abdomen was tense and tender. Peristalsis was absent. Ultrasound revealed presence of fluid in the abdominal cavity which on paracentesis was found to contain Gram positive cocci. Fluid amylase levels were high. On exploratory laparotomy, haemorrhagic oedematous pancreatitis was noticed. The patient expired on the 2nd post operative day.

  6. Chemoradiotherapy in pancreatic carcinoma

    Directory of Open Access Journals (Sweden)

    Pathy Sushmita

    2009-01-01

    Full Text Available Pancreatic cancer patients present late in their course and surgical resection as a modality of treatment is of limited value. Majority develop loco-regional failure and distant metastasis, therefore, adjuvant therapy comprising of radiotherapy and chemotherapy are useful treatment options to achieve higher loco-regional control. Specialized irradiation techniques like intra-operative radiotherapy that help to increase the total tumor dose have been used, however, controvertible survival benefit was observed. Various studies have shown improved median and overall survival with chemoradiotherapy for advanced unresectable pancreatic carcinoma. The role of new agents such as topoisomerase I inhibitors also needs further clinical investigations.

  7. Unusual complications of pancreatitis

    International Nuclear Information System (INIS)

    The computed tomography (CT) appearances of varying grades of severity of acute pancreatitis, and its complications, have been described. Body-wall ecchymosis in the periumbilical region (Cullen's sign) and loins (Grey Turner's sign), though rare, are frequently mentioned in the clinical literature. Massive, exclusively retroperitoneal, involvement is also exceedingly rare. Computed tomography depiction of these signs is sparsely documented. The CT documentation, with clinico-surgical correlation, of two cases of severe acute pancreatitis with these unusual complications, is presented. 9 refs., 3 figs

  8. MR imaging of pancreatic diseases

    Energy Technology Data Exchange (ETDEWEB)

    Ito, Katsuyoshi E-mail: itokatsu@po.cc.yamaguchi-u.ac.jp; Koike, Shinji; Matsunaga, Naofumi

    2001-05-01

    This article presents current MR imaging techniques for the pancreas, and review a spectrum of MR imaging features of various pancreatic diseases. These include: 1) congenital anomalies such as anomalous union of pancreatobiliary ducts, divisum, and annular pancreas, 2) inflammatory diseases, including acute or chronic pancreatitis with complications, groove pancreatitis, and autoimmune pancreatitis, tumor-forming pancreatitis, 3) pancreatic neoplasms, including adenocarcinoma, islet cell tumors, and cystic neoplasms (microcystic adenoma, mucinous cystic neoplasms, and intraductal mucin-producing pancreatic tumor). Particular attention is paid to technical advances in MR imaging of the pancreas such as fat-suppression, MR pancreatography (single- or multi-slice HASTE), and thin-section 3D multiphasic contrast-enhanced dynamic sequences. Imaging characteristics that may lead to a specific diagnosis or narrow the differential diagnosis are also discussed.

  9. Pancreatic disorders in inflammatory bowel disease

    Science.gov (United States)

    Antonini, Filippo; Pezzilli, Raffaele; Angelelli, Lucia; Macarri, Giampiero

    2016-01-01

    An increased incidence of pancreatic disorders either acute pancreatitis or chronic pancreatitis has been recorded in patients with inflammatory bowel disease (IBD) compared to the general population. Although most of the pancreatitis in patients with IBD seem to be related to biliary lithiasis or drug induced, in some cases pancreatitis were defined as idiopathic, suggesting a direct pancreatic damage in IBD. Pancreatitis and IBD may have similar presentation therefore a pancreatic disease could not be recognized in patients with Crohn’s disease and ulcerative colitis. This review will discuss the most common pancreatic diseases seen in patients with IBD. PMID:27574565

  10. Neoadjuvant Therapy in Pancreatic Cancer: Review Article

    OpenAIRE

    Moritz Pross; Wellner, Ulrich F.; Kim C Honselmann; Carlo Jung; Steffen Deichmann; Tobias Keck; Dirk Bausch

    2015-01-01

    We performed a literature review for neoadjuvant therapy in pancreatic cancer. We divided the results into resectable disease and local advanced pancreatic cancer. Results Neoadjuvant therapy in pancreatic cancer is safe. But currently no standard guidelines exist in neoadjuvant approaches on pancreatic cancer. For local advanced pancreatic cancer the available data tends to show a positive effect on survival rates for neoadjuvant approaches.

  11. Studies of pancreatic carcinogenesis

    Institute of Scientific and Technical Information of China (English)

    JI Yu-bin; PANG Lin-lin; YU Lei; YANG Hai-fan; LIU Guang-da; LI Hai-jiao

    2008-01-01

    Pancreatic carcinoma is the most common pancreatic neoplasm characterized by latentmorbidit, poor prognosis, high mortality rate and limited choice of treatment. Quite a lot studies focused on its pathogenesis, and showed molecular genetic alterations, which derived of genetic and environmental factors and played an important role in tumorigenesis. Recently, more and more findings laid particular emphasis on the changes of gene molecule and some were confirmed in vitro and in vivo. In this paper, we made a review and summarized the arked molecular changes and signalings of the four pathways to understand their functions in Pancreatic carcinoma. The most important changes concentrate on K-RAS, p16 INK4α, P53 and SMAD4 gene, secondly, the changes of pl4ARF, TGF-β, LKB1 /STK11, BRCA2 and growth factor Hedgehog and Notch path way and Telomere also play a important role in pancreatic carcinoma. The vast majority (83%) of pancreatic carcinomas had a distinctive genetic fingerprint, comprising activation of the K-ras oncogene and inactivation of the p 16 gene, generally also accompanied by alterations in the p53 gene (in 76 % of the tumors). The activation of K-ras appears nearly to be a prerequisite for the development of pancreatic carcinoma. Also, the binary alteration of K-ras and p16 is an extremely uncommon combination among other human tumor types. This particular genetic imprint of pancreatic carcinomas could have diagnostic utility in the evaluation of patients with metastatic adenocarcinoma of unknown primary origin. The evaluation of genetic alterations as they naturally occur in humantumors allows the formulation of hypotheses concerning the biological processes that involve human tumongenesis. A central tenet of tumori genesis, that positive selection is exerted upon those tumor cells that alterrate-limiting regulatory pathways, implies that mutation of one gene abrogates the need for inactivation of another gene in the same tumor suppressive pathway. It

  12. Efecto de N-acetilcisteína y glucocorticoides sobre la expresión de moléculas de adhesión y quimiocinas durante la pancreatitis aguda edematosa y necrotizante

    OpenAIRE

    Yubero Benito, Sara

    2010-01-01

    [ES]Esta tesis tiene como finalidad estudiar en pancreatitis aguda edematosa y necrotizante los efectos de un tratamiento antioxidante (N-Acetilcisteína), y otro anti-inflamatorio (Dexametasona), sobre la expresión de quimiocinas y moléculas de adhesión en diferentes niveles biológicos (célula acinar, tejido pancreático, plasma, leucocitos circulantes y pulmón) y relacionar los resultados con la efectividad de dichos tratamientos en la evolución de la enfermedad. [EN]This thesis aims to st...

  13. Environmental risk factors for chronic pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Nitsche, Claudia; Simon, Peter; Weiss, F Ulrich; Fluhr, Gabriele; Weber, Eckhard; Gärtner, Simone; Behn, Claas O; Kraft, Matthias; Ringel, Jörg; Aghdassi, Ali; Mayerle, Julia; Lerch, Markus M

    2011-01-01

    Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ∼10% of heavy drinkers develop chronic pancreatitis not only suggests that other environmental factors, such as tobacco smoke, are potent additional risk factors, but also that the genetic component of pancreatitis is more common than previously presumed. Either disease-causing or protective traits have been indentified for mutations in different trypsinogen genes, the gene for the trypsin inhibitor SPINK1, chymotrypsinogen C, and the cystic fibrosis transmembane conductance regulator (CFTR). Other factors that have been proposed to contribute to pancreatitis are obesity, diets high in animal protein and fat, as well as antioxidant deficiencies. For the development of pancreatic cancer, preexisting chronic pancreatitis, more prominently hereditary pancreatitis, is a risk factor. The data on environmental risk factors for pancreatic cancer are, with the notable exception of tobacco smoke, either sparse, unconfirmed or controversial. Obesity appears to increase the risk of pancreatic cancer in the West but not in Japan. Diets high in processed or red meat, diets low in fruits and vegetables, phytochemicals such as lycopene and flavonols, have been proposed and refuted as risk or protective factors in different trials. The best established and single most important risk factor for cancer as well as pancreatitis and the one to clearly avoid is tobacco smoke. PMID:21734390

  14. Loss of the BRCA1-interacting helicase BRIP1 results in abnormal mammary acinar morphogenesis.

    Directory of Open Access Journals (Sweden)

    Kazuhiro Daino

    Full Text Available BRIP1 is a DNA helicase that directly interacts with the C-terminal BRCT repeat of the breast cancer susceptibility protein BRCA1 and plays an important role in BRCA1-dependent DNA repair and DNA damage-induced checkpoint control. Recent studies implicate BRIP1 as a moderate/low-penetrance breast cancer susceptibility gene. However, the phenotypic effects of BRIP1 dysfunction and its role in breast cancer tumorigenesis remain unclear. To explore the function of BRIP1 in acinar morphogenesis of mammary epithelial cells, we generated BRIP1-knockdown MCF-10A cells by short hairpin RNA (shRNA-mediated RNA interference and examined its effect in a three-dimensional culture model. Genome-wide gene expression profiling by microarray and quantitative RT-PCR were performed to identify alterations in gene expression in BRIP1-knockdown cells compared with control cells. The microarray data were further investigated using the pathway analysis and Gene Set Enrichment Analysis (GSEA for pathway identification. BRIP1 knockdown in non-malignant MCF-10A mammary epithelial cells by RNA interference induced neoplastic-like changes such as abnormal cell adhesion, increased cell proliferation, large and irregular-shaped acini, invasive growth, and defective lumen formation. Differentially expressed genes, including MCAM, COL8A1, WIPF1, RICH2, PCSK5, GAS1, SATB1, and ELF3, in BRIP1-knockdown cells compared with control cells were categorized into several functional groups, such as cell adhesion, polarity, growth, signal transduction, and developmental process. Signaling-pathway analyses showed dysregulation of multiple cellular signaling pathways, involving LPA receptor, Myc, Wnt, PI3K, PTEN as well as DNA damage response, in BRIP1-knockdown cells. Loss of BRIP1 thus disrupts normal mammary morphogenesis and causes neoplastic-like changes, possibly via dysregulating multiple cellular signaling pathways functioning in the normal development of mammary glands.

  15. Ca²⁺ signaling and regulation of fluid secretion in salivary gland acinar cells.

    Science.gov (United States)

    Ambudkar, Indu S

    2014-06-01

    Neurotransmitter stimulation of plasma membrane receptors stimulates salivary gland fluid secretion via a complex process that is determined by coordinated temporal and spatial regulation of several Ca(2+) signaling processes as well as ion flux systems. Studies over the past four decades have demonstrated that Ca(2+) is a critical factor in the control of salivary gland function. Importantly, critical components of this process have now been identified, including plasma membrane receptors, calcium channels, and regulatory proteins. The key event in activation of fluid secretion is an increase in intracellular [Ca(2+)] ([Ca(2+)]i) triggered by IP3-induced release of Ca(2+) from ER via the IP3R. This increase regulates the ion fluxes required to drive vectorial fluid secretion. IP3Rs determine the site of initiation and the pattern of [Ca(2+)]i signal in the cell. However, Ca(2+) entry into the cell is required to sustain the elevation of [Ca(2+)]i and fluid secretion. This Ca(2+) influx pathway, store-operated calcium influx pathway (SOCE), has been studied in great detail and the regulatory mechanisms as well as key molecular components have now been identified. Orai1, TRPC1, and STIM1 are critical components of SOCE and among these, Ca(2+) entry via TRPC1 is a major determinant of fluid secretion. The receptor-evoked Ca(2+) signal in salivary gland acinar cells is unique in that it starts at the apical pole and then rapidly increases across the cell. The basis for the polarized Ca(2+) signal can be ascribed to the polarized arrangement of the Ca(2+) channels, transporters, and signaling proteins. Distinct localization of these proteins in the cell suggests compartmentalization of Ca(2+) signals during regulation of fluid secretion. This chapter will discuss new concepts and findings regarding the polarization and control of Ca(2+) signals in the regulation of fluid secretion.

  16. Biopsy follow-up in patients with isolated atypical small acinar proliferation (ASAP in prostate biopsy

    Directory of Open Access Journals (Sweden)

    Luca Leone

    2014-12-01

    Full Text Available The incidence of prostate cancer (PCA was evaluated in 155 patients with isolated Atypical Small Acinar Proliferation (ASAP found on initial prostate biopsy, after a medium-term follow-up (40 months with at least one re-biopsy. Clinical and histological data were analysed. Cancer was detected in 81 of 155 (52.3%. The cancer detection rate was 71.6%, 91.3%, 97.5%, 100% at the 1st re-biopsy, 2nd, 3rd, and 4th rebiopsy respectively. At the uni- and multivariate analyses, prostate volume (≤ 30 cc, transition zone volume (≤ 10 cc, small core length at the initial biopsy (≤ 10 mm and few number of cores at initial biopsy (≤ 8 are predictive of cancer. Furthermore, tumour characteristics on the whole surgical specimens was assessed in 30 men: 13 of 30 (43 % had clinically relevant cancer (volume > 0.5 ml or/and Gleason score ≥ 7, or pT3. Most of relevant cancers were detected in the distal apex, anterior gland and midline. These anatomical sites could be under-sampled at the initial biopsy using the transrectal approach. Our data suggest that follow-up biopsy is recommended in all cases of isolated ASAP detected after biopsy using endfire transrectal probe. The re-biopsy strategy should increase the number of cores (or a saturation biopsy, focusing on area of ASAP in the initial biopsy, but also including the under-sampled areas (anterior gland, distal apex and midline to detect clinically relevant cancers.

  17. Apical Ca2+-activated potassium channels in mouse parotid acinar cells.

    Science.gov (United States)

    Almassy, Janos; Won, Jong Hak; Begenisich, Ted B; Yule, David I

    2012-02-01

    Ca(2+) activation of Cl and K channels is a key event underlying stimulated fluid secretion from parotid salivary glands. Cl channels are exclusively present on the apical plasma membrane (PM), whereas the localization of K channels has not been established. Mathematical models have suggested that localization of some K channels to the apical PM is optimum for fluid secretion. A combination of whole cell electrophysiology and temporally resolved digital imaging with local manipulation of intracellular [Ca(2+)] was used to investigate if Ca(2+)-activated K channels are present in the apical PM of parotid acinar cells. Initial experiments established Ca(2+)-buffering conditions that produced brief, localized increases in [Ca(2+)] after focal laser photolysis of caged Ca(2+). Conditions were used to isolate K(+) and Cl(-) conductances. Photolysis at the apical PM resulted in a robust increase in K(+) and Cl(-) currents. A localized reduction in [Ca(2+)] at the apical PM after photolysis of Diazo-2, a caged Ca(2+) chelator, resulted in a decrease in both K(+) and Cl(-) currents. The K(+) currents evoked by apical photolysis were partially blocked by both paxilline and TRAM-34, specific blockers of large-conductance "maxi-K" (BK) and intermediate K (IK), respectively, and almost abolished by incubation with both antagonists. Apical TRAM-34-sensitive K(+) currents were also observed in BK-null parotid acini. In contrast, when the [Ca(2+)] was increased at the basal or lateral PM, no increase in either K(+) or Cl(-) currents was evoked. These data provide strong evidence that K and Cl channels are similarly distributed in the apical PM. Furthermore, both IK and BK channels are present in this domain, and the density of these channels appears higher in the apical versus basolateral PM. Collectively, this study provides support for a model in which fluid secretion is optimized after expression of K channels specifically in the apical PM.

  18. Hyperamylasaemia: pathognomonic to pancreatitis?

    OpenAIRE

    Burden, Sam; Poon, Anna Sau Kuk; Masood, Kausar; Didi, Mohamed

    2013-01-01

    An 82-year-old woman, presented with a history of vomiting, abdominal mass and a significantly raised amylase, but no clinical evidence of pancreatitis. Abdominal ultrasound and CT scans showed an ovarian tumour, and no evidence of pancreatitis—as is often associated with a raised amylase. The patient underwent bilateral ovariectomy and hysterectomy and made a good recovery.

  19. Pancreatic Cancer: A Review.

    Science.gov (United States)

    Yabar, Cinthya S; Winter, Jordan M

    2016-09-01

    Pancreatic cancer is now the third leading cause of cancer related deaths in the United States, yet advances in treatment options have been minimal over the past decade. In this review, we summarize the evaluation and treatments for this disease. We highlight molecular advances that hopefully will soon translate into improved outcomes. PMID:27546841

  20. Radioimmunoassay of pancreatic glucagon

    International Nuclear Information System (INIS)

    The author presents some of the problems and concepts related to the development of a radioimmunoassay of pancreatic glucagon. A specific derivatization of glucagon for raising specific anti-glucagon antisera is introduced, and special procedures for diminishing the non-specific effect are outlined. (G.T.H.)

  1. Chronic Pancreatitis in Children

    Science.gov (United States)

    ... fewer than 10 grams of fat. About 20 potato chips contain 10 grams of fat, so it takes discipline to make sure to stay within this range. Patients who have lost the ability to digest food will be prescribed pills containing pancreatic enzymes to help with digestion. They may also be ...

  2. Pancreatic and hepatobiliary cancers.

    Science.gov (United States)

    Buck, Andreas K; Herrmann, Ken; Eckel, Florian; Beer, Ambros J

    2011-01-01

    Morphology-based imaging modalities have replaced classical conventional nuclear medicine modalities for detection of liver or pancreatic lesions. With positron emission tomography and the glucose analog F-18 fluorodeoxyglucose (FDG), a sensitive and specific modality for the detection of hepatic metastases and extrahepatic tumor deposits from hepatocellular or pancreatic cancer is available. F-18 FDG PET can increase the accuracy of staging primary tumors of the liver or the pancreas, and can be used for response monitoring. Radiopharmaceuticals such as Ga-68 DOTATOC and F-18 DOPA allow the specific detection of neuroendocrine pancreatic tumors and their metastatic deposits. Hybrid scanners such as PET-CT integrate morphologic and metabolic information, and allow to increase the sensitivity and specificity of noninvasive imaging in many tumor entities. The development of specific radiopharmaceuticals and technical innovations such as SPECT-CT has increased the reliability of conventional scintigraphic imaging. This chapter focuses on the use of PET-CT in hepatobiliary and pancreatic cancers. PMID:21331938

  3. Pancreatic Cancer Stage 4

    Science.gov (United States)

    ... lung, liver, and peritoneal cavity. An inset shows cancer cells spreading from the pancreas, through the blood and lymph system, to another ... abdomen that contains the intestines, stomach, and liver). Cancer may also have spread to ... pancreas or to lymph nodes. Stage IV pancreatic cancer. ...

  4. Study on chronic pancreatitis and pancreatic cancer using MRS and pancreatic juice samples

    Institute of Scientific and Technical Information of China (English)

    Jian Wang; Chao Ma; Zhuan Liao; Bing Tian; Jian-Ping Lu

    2011-01-01

    AIM: To investigate the markers of pancreatic diseases and provide basic data and experimental methods for the diagnosis of pancreatic diseases. METHODS: There were 15 patients in the present study, among whom 10 had pancreatic cancer and 5, chronic pancreatitis. In all patients, pancreatic cancer or chronic pancreatitis was located on the head of the p-a-ncreas. Pathology data of all pa tients was confirmed by biopsy and surgery. Among the 10 patients with pancreatic cancer, 3 people had a medical history of longterm alcohol consumption. Of 5 patients with chronic pancreatitis, 4 men suffered from alcoholic chronic pancreatitis. Pancreatic juice samples were obtained from patients by endoscopic retrograde cholangiopancreatography. Magnetic resonance spectroscopyn was performed on an 11.7-T scanner (Bruker DRX-500) using Call-Purcell-Meiboom-Gill pulse sequences. The parameters were as follows: spectral width, 15 KHz; time domain, 64 K; number of scans, 512; and acquisition time, 2.128 s. RESULTS: The main component of pancreatic juice included leucine, iso-leucine, valine, lactate, alanine, acetate, aspartate, lysine, glycine, threonine, tyrosine, histidine, tryptophan, and phenylalanine. On performing 1D 1H and 2D total correlation spectroscopy, we found a triplet peak at the chemical shift of 1.19 ppm, which only appeared in the spectra of pancreatic juice obtained from patients with alcoholic chronic pancreatitis. This triplet peak was considered the resonance of the methyl of ethoxy group, which may be associated with the metabolism of alcohol in the pancreas. CONCLUSION: The triplet peak, at the chemical shift of 1.19 ppm is likely to be the characteristic metabolite of alcoholic chronic pancreatitis.

  5. CT-Guided Pancreatic Percutaneous Fine-Needle Biopsy in Differential Diagnosis between Pancreatic Cancer and Chronic Pancreatitis

    OpenAIRE

    Michele Carlucci; Alessandro Zerbi; Danilo Parolini; Sandro Sironi; Angelo Vanzulli; Carlo Staudacher; Agostino Faravelli; Paola Garancini; Alessandro del Maschio; Valerio di Carlo

    1989-01-01

    Differential diagnosis between pancreatic cancer and chronic pancreatitis is still difficult to establish. In 63 patients with suspected pancreatic neoplasm we performed: serum CA 19-9 assessment, abdominal ultrasound, CT scan and CT-guided pancreatic percutaneous fine-needle biopsy. The conclusive diagnosis was pancreatic cancer in 40 patients and chronic pancreatitis in 23 patients. With regard to the differential diagnosis, sensitivity and specificity were respectively 80% and ...

  6. Patient Derived Cancer Cell Lines in Identifying Molecular Changes in Patients With Previously Untreated Pancreatic Cancer Receiving Gemcitabine Hydrochloride-Based Chemotherapy

    Science.gov (United States)

    2016-10-18

    Pancreatic Ductal Adenocarcinoma; Stage IA Pancreatic Cancer; Stage IB Pancreatic Cancer; Stage IIA Pancreatic Cancer; Stage IIB Pancreatic Cancer; Stage III Pancreatic Cancer; Stage IV Pancreatic Cancer

  7. Gramicidin-perforated Patch Recording Revealed the Oscillatory Nature of Secretory Cl− Movements in Salivary Acinar Cells

    OpenAIRE

    Sugita, Makoto; Hirono, Chikara; Shiba, Yoshiki

    2004-01-01

    Elevations of cytoplasmic free calcium concentrations ([Ca2+]i) evoked by cholinergic agonists stimulate isotonic fluid secretion in salivary acinar cells. This process is driven by the apical exit of Cl− through Ca2+-activated Cl− channels, while Cl− enters the cytoplasm against its electrochemical gradient via a loop diuretic-sensitive Na+-K+-2Cl− cotransporter (NKCC) and/or parallel operations of Cl−-HCO3 − and Na+-H+ exchangers, located in the basolateral membrane. To characterize the con...

  8. Acute Pancreatitis: Surgery, Pathophysiology and Probiotic Prophylaxis

    NARCIS (Netherlands)

    Minnen, L.P. van

    2006-01-01

    Acute pancreatitis is a challenging disease with a clinical course that is often difficult to predict. In severe acute pancreatitis, mortality increases significantly if intestinal bacteria translocate from the intestine and infect pancreatic necrosis. Surgical and prophylactic treatment strategies

  9. Exocrine pancreatic enzyme and calcium secretion in health and pancreatitis.

    OpenAIRE

    Clain, J E; Barbezat, G O; Marks, I N

    1981-01-01

    Calcium, enzyme, and total protein secretion were measured in secretin stimulated pancreatic juice in health, "early" chronic pancreatitis, and in chronic calcific pancreatitis. Increased concentrations of trypsin, total protein, and calcium, and increased outputs of calcium and protein were shown to be present in the "early" stages of the disease, indicating that an environment conducive to the formation of protein plugs and possibly later calcification already exists.

  10. Groove Pancreatitis: A Rare form of Chronic Pancreatitis

    OpenAIRE

    Bharivi Jani; Fadi Rzouq; Shreyas Saligram; Atta Nawabi; Marian Nicola; Katie Dennis; Carly Ernst; Ali Abbaszadeh; John Bonino; Mojtaba Olyaee

    2015-01-01

    Context: Groove pancreatitis is a rare form of chronic pancreatitis affecting the "groove" of the pancreas among the pancreatic head, duodenum, and common bile duct. The exact cause is unknown, although there are associations with long-term alcohol abuse, smoking, peptic ulcer disease, heterotopic pancreas, gastric resection, biliary disease, and anatomical or functional obstruction of the minor papilla. The diagnosis can be challenging. Endoscopic ultrasound (EUS) and magnetic resonance chol...

  11. Role of pancreatic stellate cells in chemoresistance in pancreatic cancer

    OpenAIRE

    McCarroll, Joshua A.; Naim, Stephanie; Sharbeen, George; Russia, Nelson; Lee, Julia; Kavallaris, Maria; Goldstein, David; Phillips, Phoebe A.

    2014-01-01

    Pancreatic cancer is highly chemoresistant. A major contributing factor is the characteristic extensive stromal or fibrotic reaction, which comprises up to 90% of the tumor volume. Over the last decade there has been intensive research into the role of the pro-fibrogenic pancreatic stellate cells (PSCs) and their interaction with pancreatic cancer cells. As a result of the significant alterations in the tumor microenvironment following activation of PSCs, tumor progression, and chemoresistanc...

  12. Magnetic resonance imaging for acute pancreatitis

    OpenAIRE

    Xiao, Bo; Zhang, Xiao-Ming

    2010-01-01

    Acute pancreatitis is characterized by acute chemical injury of the pancreatic parenchyma and peripancreatic tissue. The increased frequency of death in acute pancreatitis is directly correlated with the degree and progress of pancreatic necrosis. Moreover, the occurrence of some local complications in acute pancreatitis, such as pancreatic hemorrhage, peripancreatic abscess or large pseudocyst, and pseudoaneurysm, could influence the choice of treatment for these patients. Magnetic resonance...

  13. Contemporary Management of Acute Biliary Pancreatitis

    OpenAIRE

    Orhan Ozkan

    2014-01-01

    Acute biliary pancreatitis is one of the major causes of acute pancreatitis.Gallstones, biliary sludge and microlithiasis, especially in pancreatitis without detectable reason, can be the cause of acute pancreatitis. Acute biliary pancreatitis has many controversions in the literature, and its classification and guidelines are being updated very frequently. Atlanta classifications which determine the definitions and guidelines about acute pancreatitis were renewed and published in 2013. It ha...

  14. Molecular mechanisms of pancreatic stone formation in chronic pancreatitis.

    Directory of Open Access Journals (Sweden)

    Shigeru B.H. Ko

    2012-11-01

    Full Text Available Chronic pancreatitis (CP is a progressive inflammatory disease in which the pancreatic secretory parenchyma is destroyed and replaced by fibrosis. The presence of intraductal pancreatic stone(s is important for the diagnosis of CP; however, the precise molecular mechanisms of pancreatic stone formation in CP were left largely unknown. CFTR is a chloride channel expressed in the apical plasma membrane of pancreatic duct cells and plays a central role in HCO3- secretion. In previous studies, we have found that CFTR is largely mislocalized to the cytoplasm of pancreatic duct cells in all forms of CP and corticosteroids normalizes the localization of CFTR to the proper apical membrane at least in autoimmune pancreatitis. From these observations, we could conclude that the mislocalization of CFTR is a cause of protein plug formation in CP, subsequently resulting in pancreatic stone formation.Considering our observation that the mislocalization of CFTR also occurs in alcoholic or idiopathic CP, it is very likely that these pathological conditions can also be treated by corticosteroids, thereby preventing pancreatic stone formation in these patients. Further studies are definitely required to clarify these fundamental issues.

  15. Pancreatic encephalopathy- a rare complication of severe acute biliary pancreatitis

    Directory of Open Access Journals (Sweden)

    Vlad Denis Constantin

    2014-10-01

    Full Text Available Background. Pancreatic encephalopathy is a rare complication of severe acute pancreatitis, with high mortality, being difficult to diagnose and treat, thus requiring continuous research regarding its management. Materials and Methods. Of 20 patients diagnosed with severe acute pancreatitis on admission at Department of Emergency and Admission (DEA, from January 1st 2010 to March 31st 2014, 5 cases complicated by pancreatic encephalopathy were analyzed using a descriptive observational, retrospective, single-center study. Results. The study shows different types of diagnostic algorithm and therapeutical approaches, in correlation with morbidity and mortality rates. Conclusions. Our study highlighted the fact that speed is critical, early management being the key to outcome.

  16. Follicular pancreatitis: a distinct form of chronic pancreatitis-an additional mimic of pancreatic neoplasms.

    Science.gov (United States)

    Gupta, Rajib K; Xie, Bill H; Patton, Kurt T; Lisovsky, Mikhail; Burks, Eric; Behrman, Stephen W; Klimstra, David; Deshpande, Vikram

    2016-02-01

    Follicular pancreatitis is a recently described variant of chronic pancreatitis characterized clinically by the formation of a discrete pancreatic mass and histologically by the presence of florid lymphoid aggregates with reactive germinal centers. Our aim was to study the clinical and histologic features of follicular pancreatitis, as well as to critically examine potential overlap with autoimmune pancreatitis. Immunohistochemistry for Bcl-2, CD21, κ and λ light chains as well as IgG4 and IgG were performed. We found a total of 6 patients (male-female ratio, 2:1; mean age, 57 years) who fulfilled the diagnosis of follicular pancreatitis in our institutions. Four had an incidental diagnosis, while two presented with abdominal pain, fatigue, and elevated liver enzymes. On imaging, 3 patients had a discrete solid mass, whereas 2 cases showed a dilated main pancreatic duct, mimicking an intraductal pancreatic mucinous neoplasm on imaging. One patient had a lesion in the intra-pancreatic portion of the common bile duct. On histopathology, all cases showed numerous lymphoid follicles with Bcl-2-negative germinal centers either in a periductal or in a more diffuse (periductal and intra-parenchymal) fashion, but without attendant storiform fibrosis, obliterative phlebitis, or granulocytic epithelial lesions. IgG4-to-IgG ratio was <40% in 5 cases. A comparison cohort revealed germinal centers in 25% of type 1 autoimmune pancreatitis and 2% of type 2 autoimmune pancreatitis cases, but none were periductal in location. In conclusion, follicular pancreatitis, an under-recognized mimic of pancreatic neoplasms is characterized by intrapancreatic lymphoid follicles with reactive germinal centers. PMID:26563969

  17. Carbofuran-Induced Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Rizos E

    2004-01-01

    Full Text Available CONTEXT: Carbamate insecticides are widely used in commercial agriculture and home gardening. A serious side effect of organophosphate and carbamate intoxication is the development of acute pancreatitis. CASE REPORT: A 36-year-old Caucasian woman was admitted to our hospital with cholinergic crisis and pancreatitis soon after the ingestion of a carbamate insecticide (carbofuran. An abdominal CT scan disclosed pancreatic necrosis with intrapancreatic fluid collection, consistent with the development of a pancreatic pseudocyst in a subsequent CT scan. No predisposing factor for pancreatitis was evident. Pseudocholinesterase levels returned to normal 7 days later and the patient was discharged in good physical condition one month after admission. DISCUSSION: Although acute pancreatitis is not infrequent after organophosphate intoxication, it is quite rare after carbamate ingestion and has not been previously reported after carbofuran intoxication.

  18. Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2.

    Science.gov (United States)

    Peng, Shuang; Gerasimenko, Julia V; Tsugorka, Tatiana; Gryshchenko, Oleksiy; Samarasinghe, Sujith; Petersen, Ole H; Gerasimenko, Oleg V

    2016-08-01

    Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca(2+) signals, occurring as repetitive short-lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca(2+) elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca(2+) signals can be evoked by products of alcohol and fatty acids as well as bile acids. Here, we have investigated the mechanism by which l-asparaginase evokes AP. Asparaginase is an essential element in the successful treatment of acute lymphoblastic leukaemia, the most common type of cancer affecting children, but AP is a side-effect occurring in about 5-10% of cases. Like other pancreatitis-inducing agents, asparaginase evoked intracellular Ca(2+) release followed by Ca(2+) entry and also substantially reduced Ca(2+) extrusion because of decreased intracellular ATP levels. The toxic Ca(2+) signals caused extensive necrosis. The asparaginase-induced pathology depended on protease-activated receptor 2 and its inhibition prevented the toxic Ca(2+) signals and necrosis. We tested the effects of inhibiting the Ca(2+) release-activated Ca(2+) entry by the Ca(2+) channel inhibitor GSK-7975A. This markedly reduced asparaginase-induced Ca(2+) entry and also protected effectively against the development of necrosis.This article is part of the themed issue 'Evolution brings Ca(2+) and ATP together to control life and death'. PMID:27377732

  19. Calcium and adenosine triphosphate control of cellular pathology: asparaginase-induced pancreatitis elicited via protease-activated receptor 2

    Science.gov (United States)

    Peng, Shuang; Gerasimenko, Julia V.; Tsugorka, Tatiana; Gryshchenko, Oleksiy; Samarasinghe, Sujith; Gerasimenko, Oleg V.

    2016-01-01

    Exocytotic secretion of digestive enzymes from pancreatic acinar cells is elicited by physiological cytosolic Ca2+ signals, occurring as repetitive short-lasting spikes largely confined to the secretory granule region, that stimulate mitochondrial adenosine triphosphate (ATP) production. By contrast, sustained global cytosolic Ca2+ elevations decrease ATP levels and cause necrosis, leading to the disease acute pancreatitis (AP). Toxic Ca2+ signals can be evoked by products of alcohol and fatty acids as well as bile acids. Here, we have investigated the mechanism by which l-asparaginase evokes AP. Asparaginase is an essential element in the successful treatment of acute lymphoblastic leukaemia, the most common type of cancer affecting children, but AP is a side-effect occurring in about 5–10% of cases. Like other pancreatitis-inducing agents, asparaginase evoked intracellular Ca2+ release followed by Ca2+ entry and also substantially reduced Ca2+ extrusion because of decreased intracellular ATP levels. The toxic Ca2+ signals caused extensive necrosis. The asparaginase-induced pathology depended on protease-activated receptor 2 and its inhibition prevented the toxic Ca2+ signals and necrosis. We tested the effects of inhibiting the Ca2+ release-activated Ca2+ entry by the Ca2+ channel inhibitor GSK-7975A. This markedly reduced asparaginase-induced Ca2+ entry and also protected effectively against the development of necrosis. This article is part of the themed issue ‘Evolution brings Ca2+ and ATP together to control life and death’. PMID:27377732

  20. Piperine ameliorates the severity of cerulein-induced acute pancreatitis by inhibiting the activation of mitogen activated protein kinases.

    Science.gov (United States)

    Bae, Gi-Sang; Kim, Min-Sun; Jeong, Jinsu; Lee, Hye-Youn; Park, Kyoung-Chel; Koo, Bon Soon; Kim, Byung-Jin; Kim, Tae-Hyeon; Lee, Seung Ho; Hwang, Sung-Yeon; Shin, Yong Kook; Song, Ho-Joon; Park, Sung-Joo

    2011-07-01

    Piperine is a phenolic component of black pepper (Piper nigrum) and long pepper (Piper longum), fruits used in traditional Asian medicine. Our previous study showed that piperine inhibits lipopolysaccharide-induced inflammatory responses. In this study, we investigated whether piperine reduces the severity of cerulein-induced acute pancreatitis (AP). Administration of piperine reduced histologic damage and myeloperoxidase (MPO) activity in the pancreas and ameliorated many of the examined laboratory parameters, including the pancreatic weight (PW) to body weight (BW) ratio, as well as serum levels of amylase and lipase and trypsin activity. Furthermore, piperine pretreatment reduced the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 during cerulein-induced AP. In accordance with in vivo results, piperine reduced cell death, amylase and lipase activity, and cytokine production in isolated cerulein-treated pancreatic acinar cells. In addition, piperine inhibited the activation of mitogen-activated protein kinases (MAPKs). These findings suggest that the anti-inflammatory effect of piperine in cerulein-induced AP is mediated by inhibiting the activation of MAPKs. Thus, piperine may have a protective effect against AP.

  1. Approaches Towards Endogenous Pancreatic Regeneration

    OpenAIRE

    Banerjee, Meenal; Kanitkar, Meghana; Bhonde, Ramesh R.

    2005-01-01

    The phenomenon of pancreatic regeneration in mammals has been well documented. It has been shown that pancreatic tissue is able to regenerate in several species of mammal after surgical insult. This tissue is also known to have the potential to maintain or increase its β-cell mass in response to metabolic demands during pregnancy and obesity. Since deficiency in β-cell mass is the hallmark of most forms of diabetes, it is worthwhile understanding pancreatic regeneration in the context of this...

  2. Genetic Susceptibility to Pancreatic Cancer

    OpenAIRE

    Klein, Alison P

    2012-01-01

    Pancreatic cancer is the fourth leading cause of cancer death in both men and women in the United States. However, it has the poorest prognosis of any major tumor type, with a 5-yr survival rate of approximately 5%. Cigarette smoking, increased body mass index, heavy alcohol consumption, and a diagnosis of diabetes mellitus have all been demonstrated to increase risk of pancreatic cancer. A family history of pancreatic cancer has also been associated with increased risk suggesting inherited g...

  3. Acute pancreatitis complicating severe dengue

    OpenAIRE

    Vishakha Jain; O P Gupta; Tarun Rao; Siddharth Rao

    2014-01-01

    Dengue is an arthropod borne viral infection endemic in tropical and subtropical continent. Severe dengue is life threatening. Various atypical presentations of dengue have been documented. But we present a rare and fatal complication of severe dengue in form of acute pancreatitis. A 27-year-old male had presented with severe dengue in decompensated shock and with pain in abdomen due to pancreatitis. The pathogenesis of acute pancreatitis in dengue is not clearly understood, but various mecha...

  4. Nutrition Support in Acute Pancreatitis

    OpenAIRE

    Orestis Ioannidis; Athina Lavrentieva; Dimitrios Botsios

    2008-01-01

    The management of acute pancreatitis differs according to its severity. Approximately 75% of patients with acute pancreatitis have mild disease with a mortality rate below 1%. Mortality increases up to 20% if the disease progresses to its severe necrotizing form and, in the most severe cases, mortality can increase to 30-40%. Severe acute pancreatitis is usually accompanied by systemic inflammatory response syndrome (SIRS) which results in hypermetabolism with prominent protein catabolism. Ac...

  5. Helicobacter pylori and pancreatic diseases

    OpenAIRE

    Bulajic, Milutin; Panic, Nikola; Löhr, Johannes Matthias

    2014-01-01

    A possible role for Helicobacter pylori (H. pylori) infection in pancreatic diseases remains controversial. H. pylori infection with antral predomination leading to an increase in pancreatic bicarbonate output and inducing ductal epithelial cell proliferation could contribute to the development of pancreatic cancer via complex interactions with the ABO genotype, dietary and smoking habits and N-nitrosamine exposure of the host. Although the individual study data available so far is inconsiste...

  6. Pancreatic scintiphotography in diabetes mellitus

    International Nuclear Information System (INIS)

    Pancreatic scintiphotography was performed in 108 cases of patients with diabetes mellitus. Scintiphotos were taken at 30 min. after intravenous injection of approximately 200μCi of 75Se-selenomethionine using a Toshiba gamma camera. The relationship between the degree of pancreatic uptake of 75Se-selenomethionine and the types and duration of diabetes, vascular complications and the average range of fasting blood sugar levels were studied. In some cases, pancreatic scintiphotos were taken at 10, 30 and 50 min. after injection of 75Se-selenomethionine, and the degrees of the pancreatic uptake were compared on each time course. Only two out of 24 cases of insulin-dependent diabetics showed normal pancreatic scintiphotos. On the other hand, two out of 47 cases of mild diabetics treated with diet alone showed no uptake in pancreatic scintiphotos. There was a tendency toward abnormal pancreatic scintiphotos in chronic diabetics. Especially, of the 15 cases who had diabetes for more than eleven years, only one case showed a normal pancreatic scintiphoto. Abnormal pancreatic scintiphotos were found more frequently in the group of poorly controlled diabetics than in the group of well controlled diabetics. In cases showing normal pancreatic scintiphotos, diabetic retinopathy was less frequently found. Out of 36 cases which had sequential pancreatic scintiphotos, hypertension and/or arteriosclerosis were found more frequently in the 20 cases which showed a delay in reaching a plateau of the activity. However, the uptake in sequential pancreatic scintiphotos showed no definite correlation between diabetic retinopathy and other diabetic conditions. (auth.)

  7. Rapid Evolution from the First Episode of Acute Pancreatitis to Chronic Pancreatitis in Human Subjects

    OpenAIRE

    Elie Aoun; Adam Slivka; Papachristou, Dionysios J.; David C. Whitcomb; Ferga C. Gleeson; Georgios I Papachristou

    2007-01-01

    Context Growing evidence suggests that recurrent acute pancreatitis leads to chronic pancreatitis, but this sequence is seldom reported in human subjects. The sentinel acute pancreatitis event hypothesis suggests that an initial episode of acute pancreatitis is the first step in a complicated series of events ultimately leading to chronic pancreatitis. Objective To identify patients who evolved from recurrent acute pancreatitis to chronic pancreatitis. Setting The Severity of Acute Pancreatit...

  8. Profile of blood glucose and ultrastucture of beta cells pancreatic islet in alloxan compound induced rats

    Directory of Open Access Journals (Sweden)

    I Nyoman Suarsana

    2010-06-01

    Full Text Available Diabetes is marked by elevated levels of blood glucose, and progressive changes of the structure of pancreatic islet histopathology. The objective of this research was to analyse the glucose level and histophatological feature in pancreatic islet in alloxan compound induced rats. A total of ten male Spraque Dawley rats of 2 months old were used in this study. The rats were divided into two groups: (1 negative control group (K-, and (2 positif induced alloxan group (diabetic group =DM. The rats were induced by a single dose intraperitonial injection of alloxan compound 120 mg/kg of body weight. The treatment was conducted for 28 days. Blood glucose levels of rats were analysed at 0, 4, 7, 14, 21, and 28 days following treatment. At the end of the experiment, rats were sacrificed by cervical dislocation. Pancreas was collected for analysis of histopathological study by Immunohistochemical technique, and ultrastructural study using transmission electron microscope (TEM. The result showed that Langerhans islet of diabetic rat (rat of DM group showed a marked reduction of size, number of Langerhans islet of diabetic rat decrease, and characterized by hyperglycemic condition. By using TEM, beta cells of DM group showed the rupture of mitochondrial membrane, the lost of cisternal structure of inner membrane of mitocondria, reduction of insulin secretory granules, linkage between cells acinar with free Langerhans islet, and the caryopicnotic of nucleus.

  9. Antioxidant activity of Inonotus obliquus polysaccharide and its amelioration for chronic pancreatitis in mice.

    Science.gov (United States)

    Hu, Yang; Sheng, Yi; Yu, Min; Li, Koukou; Ren, Guangming; Xu, Xiuhong; Qu, Juanjuan

    2016-06-01

    Inonotus obliquus polysaccharide (IOP) was extracted by water with a yield of 9.83% and purified by an anion-exchange DEAE cellulose column and Sephadex G-200 gel with a polysaccharide content of 98.6%. The scavenging activities for 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and hydroxyl radicals of IOP were 82.3% and 81.3% respectively at a concentration of 5 mg/mL. IOP was composed of Man, Rha, Glu, Gal, Xyl and Ara in a molar ratio of 9.81:3.6:29.1:20.5:21.6:5.4 respectively. The gel permeation chromatography indicated that IOP was a homogeneous polysaccharide with molecular weight of 32.5 kDa. IOP helped to alleviate pancreatic acinar atrophy and weight loss for chronic pancreatitis (CP) mice induced by Diethyldithiocarbamate (DDC). The SOD level was increased most by IOP-H treatment (400 mg/kg body weight). MDA, IL-1β and LDH were significantly decreased by IOP treatment, especially hydroxyproline, IFN-γ and AMS levels were decreased 39.18%, 37.82% and 41.57% by IOP-H treatment respectively compared to MC group. In conclusion, IOP possessed strong antioxidant activity for scavenging free radicals in vitro and vivo which could be propitious to CP therapy in mice. PMID:26955745

  10. Early management of acute pancreatitis.

    Science.gov (United States)

    Schepers, Nicolien J; Besselink, Marc G H; van Santvoort, Hjalmar C; Bakker, Olaf J; Bruno, Marco J

    2013-10-01

    Acute pancreatitis is the most common gastro-intestinal indication for acute hospitalization and its incidence continues to rise. In severe pancreatitis, morbidity and mortality remains high and is mainly driven by organ failure and infectious complications. Early management strategies should aim to prevent or treat organ failure and to reduce infectious complications. This review addresses the management of acute pancreatitis in the first hours to days after onset of symptoms, including fluid therapy, nutrition and endoscopic retrograde cholangiography. This review also discusses the recently revised Atlanta classification which provides new uniform terminology, thereby facilitating communication regarding severity and complications of pancreatitis.

  11. An overview of hereditary pancreatitis.

    Science.gov (United States)

    Rebours, Vinciane; Lévy, Philippe; Ruszniewski, Philippe

    2012-01-01

    Hereditary pancreatitis is a rare cause of chronic pancreatitis. The prevalence was evaluated to 0.3/100000 in Western Countries. Genetic disorders are due to mutations of the PRSS1 gene on the long arm of the chromosome 7, encoding for the cationic trypsinogen. The inheritance pattern is autosomal dominant with an incomplete penetrance (80%). Since 1996, more than 30 mutations were found. The three more common mutations are R122H, N29I and A16V. First symptoms begin since childhood, mainly before 10 years old. Main symptoms are pancreatic pain and acute pancreatitis (>70%). CP morphological changes as pancreatic calcifications are diagnosed at a median age of 22-25 years. Exocrine and endocrine pancreatic insufficiency occurred in 34% and 26% at a median age of 29 and 38 years. No clinical differences exist according to the mutation type. No excess of mortality in hereditary pancreatitis population compared to general population was found, despite a real risk of cancer. The cumulative risks of pancreatic cancer at 50, 60 and, 75 years are 10%, 18.7% and, 53.5%, respectively. The relative risk of cancer increases in smokers and is evaluated to 8.55. Hereditary pancreatitis diagnosis permits to propose an adapted management in expert centres.

  12. Helicobacter pylori and pancreatic diseases

    Institute of Scientific and Technical Information of China (English)

    Milutin; Bulajic; Nikola; Panic; Johannes; Matthias; L?hr

    2014-01-01

    A possible role for Helicobacter pylori(H. pylori) infec-tion in pancreatic diseases remains controversial. H. pylori infection with antral predomination leading to an increase in pancreatic bicarbonate output and induc-ing ductal epithelial cell proliferation could contribute to the development of pancreatic cancer via complex interactions with the ABO genotype, dietary and smok-ing habits and N-nitrosamine exposure of the host. Although the individual study data available so far is inconsistent, several meta-analyses have reported an increased risk for pancreatic cancer among H. pylori seropositive individuals. It has been suggested that H. pylori causes autoimmune pancreatitis due to molecu-lar mimicry between H. pylori a-carbonic anhydrase(a-CA) and human CA type Ⅱ, and between H. pylori plasminogen-binding protein and human ubiquitin-protein ligase E3 component n-recognin 2, enzymes that are highly expressed in the pancreatic ductal andacinar cells, respectively. Future studies involving large numbers of cases are needed in order to examine the role of H. pylori in autoimmune pancreatitis more fully. Considering the worldwide pancreatic cancer burden, as well as the association between autoimmune pan-creatitis and other autoimmune conditions, a complete elucidation of the role played by H. pylori in the gen-esis of such conditions could have a substantial impact on healthcare.

  13. Efeito da hipertermia na pancreatite aguda grave experimental Effects of hyperthermia on experimental severe acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Maurício Gustavo Ieri Yamanari

    2007-02-01

    Full Text Available OBJETIVO: O objetivo deste estudo é avaliar os efeitos da hipertermia na pancreatite aguda (PA grave experimental induzida por ácido taurocólico. MÉTODO: A PA grave foi induzida pela injeção retrógrada de ácido taurocólico a 2,5% ou 5% no ducto pancreático principal. Após a indução, os animais foram colocados numa gaiola contendo duas lâmpadas de 100 W. A temperatura corporal foi aumentada para 39,5ºC e mantida neste nível por 45 minutos. Foram estudados taxa de mortalidade em 72 horas, permeabilidade vascular no pâncreas, porcentagem de água no tecido pancreático, amilase sérica, histologia (edema, necrose acinar e infiltrado inflamatório e níveis séricos de IL-6 e IL-10. RESULTADOS: Não houve alteração em nenhum dos parâmetros avaliados. CONCLUSÃO: Não há benefício da hipertermia na PA grave experimental induzida por ácido taurocólico.OBJECTIVE: The aim of this study is to evaluate the effects of hyperthermia post-treatment on taurocholate-induced severe acute pancreatitis (AP in rats. METHOD: Severe AP was induced by retrograde injection of 2,5% or 5% taurocholate solution into the main pancreatic duct. After the AP induction, animals were heated in a cage with two 100 W lamps. Body temperature was increased to 39ºC and maintained at that level for 45 minutes. 72-hours mortality rate, amylase serum levels, histology (edema, acinar necrosis and inflammatory infiltrate, vascular permeability, pancreatic water content and serum levels of IL-6 and IL-1 were determinated. RESULTS: Hyperthermia post-treatment on severe AP showed no evidence of alteration in all evaluated parameters. CONCLUSION: The findings suggest no beneficial effect of the thermal stress on inflammatoy edema and mortality rate in taurocholate AP model.

  14. Membrane lipid composition of pancreatic AR42J cells: modification by exposure to different fatty acids.

    Science.gov (United States)

    Audi, Nama'a; Mesa, María D; Martínez, María A; Martínez-Victoria, Emilio; Mañas, Mariano; Yago, María D

    2007-04-01

    Dietary fat type influences fatty acids in rat pancreatic membranes, in association with modulation of secretory activity and cell signalling in viable acini. We aimed to confirm whether AR42J cells are a valid model to study the interactions between lipids and pancreatic acinar cell function. For this purpose we have (i) compared the baseline fatty acid composition of AR42J cells with that of pancreatic membranes from rats fed a standard chow; (ii) investigated if fatty acids in AR42J membranes can be modified in culture; and (iii) studied if similar compositional variations that can be evoked in rats when dietary fat type is altered occur in AR42J cells. Weaning Wistar rats were fed for 8 weeks either a commercial chow (C) or semi-purified diets containing virgin olive oil (VOO) or sunflower oil (SO) as fat source. AR42J cells were incubated for 72 hrs in medium containing unmodified fetal calf serum (FCS, AR42J-C cells), FCS enriched with 18:1 n-9 (AR42J-O cells), or FCS enriched with 18:2 n-6 (AR42J-L cells). Fatty acids in crude membranes from rat pancreas and AR42J cells were determined by gas-liquid chromatography. Differences in membrane fatty acids between C rats and AR42J-C cells can be explained in part by variations in the amount of fatty acids in the extracellular environment. Supplementation of FCS with 18:1 n-9 or 18:2 n-6 changed the fatty acid spectrum of AR42J cells in a manner that resembles the pattern found, respectively, in VOO and SO rats, although AR42J-L cells were unable to accumulate 20:4 n-6. The AR42J cell line can be a useful tool to assess the effect of membrane compositional changes on acinar cell function. However, differences in baseline characteristics, and perhaps fatty acid metabolism, indicate that results obtained in AR42J cells should be confirmed with experiments in the whole animal.

  15. Pancreatic Cancer in 2014

    Directory of Open Access Journals (Sweden)

    Serafim Kaltsas

    2014-03-01

    Full Text Available 5-FU/LV: 5-fluorouracil and leucovorin; FOLFIRINOX: 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin; FOLFOX: 5-flouorouracil, leucovorin and oxaliplatin; HA: hyaluronic acid; JAK: Janus kinase; MM-398: irinotecan sucrosofate; MPACT: Metastatic Pancreatic Adenocarcinoma Clinical Trial; PARP: poly (ADP-ribose polymerase; PEGPH: pegylated recombinant human hyaluronidase; PSCA: prostate stem cell antigen; SN-38: active metabolite of irinotecan; SPARC: secreted protein acidic and rich in cysteine

  16. Post-partum pancreatitis.

    OpenAIRE

    Pai P; Shah H; Samsi A

    1993-01-01

    Acute pancreatitis in pregnancy and post-partum period, rarely encountered in surgical practice, can have a lethal effect on the mother and the foetus. We report here a case of a 35 year old tertigravida who presented with high grade fever, abdominal pain with distension, tachycardia and tachypnoea. Chest examination and X-rays were suggestive of pneumonia. The abdomen was tense and tender. Peristalsis was absent. Ultrasound revealed presence of fluid in the abdominal cavity which on paracent...

  17. Inhibitors of pancreatic lipase

    OpenAIRE

    Lunagariya, Nitin A.; Patel, Neeraj K.; Jagtap, Sneha C.; Bhutani, Kamlesh K.

    2014-01-01

    Obesity is a disorder of lipid metabolism and continues to be a global problem, ranking fifth for deaths worldwide. It also leads to diabetes, cardiovascular disorders, musculoskeletal disorders and some types of cancer. Obesity is regarded as the output of a long-term imbalance between energy intake and energy expenditure. Digestion and absorption of dietary lipids by pancreatic lipase, a major source of excess calorie intake, can be targeted for development of anti-obesity agents. Being the...

  18. [Acute pancreatitis and pregnancy].

    Science.gov (United States)

    Scollo, P; Licitra, G

    1993-12-01

    Aetiologic factors (gallstones, hyperlipidemia I-IV, hypertriglyceridaemia) make their occurrence, mainly, in the third trimester of gestation. Two cases of acute pancreatitis in pregnancy are described; in both cases patients referred healthy diet, no habit to smoke and no previous episode of pancreatitis. An obstructive pathology of biliary tract was the aetiologic factor. Vomiting, upper abdominal pain are aspecific symptoms that impose a differential diagnosis with acute appendicitis, cholecystitis and obstructive intestinal pathology. Laboratory data (elevated serum amylase and lipase levels) and ultrasonography carry out an accurate diagnosis. The management of acute pancreatitis is based on the use of symptomatic drugs, a low fat diet alternated to the parenteral nutrition when triglycerides levels are more than 28 mmol/L. Surgical therapy, used only in case of obstructive pathology of biliary tract, is optimally collected in the third trimester or immediately after postpartum. Our patients, treated only medically, delivered respectively at 38th and 40th week of gestation. Tempestivity of diagnosis and appropriate therapy permit to improve prognosis of a pathology that, although really associated with pregnancy, presents high maternal mortality (37%) cause of complications (shock, coagulopathy, acute respiratory insufficiency) and fetal (37.9%) by occurrence of preterm delivery.

  19. [Acute pancreatitis and pregnancy].

    Science.gov (United States)

    Scollo, P; Licitra, G

    1993-12-01

    Aetiologic factors (gallstones, hyperlipidemia I-IV, hypertriglyceridaemia) make their occurrence, mainly, in the third trimester of gestation. Two cases of acute pancreatitis in pregnancy are described; in both cases patients referred healthy diet, no habit to smoke and no previous episode of pancreatitis. An obstructive pathology of biliary tract was the aetiologic factor. Vomiting, upper abdominal pain are aspecific symptoms that impose a differential diagnosis with acute appendicitis, cholecystitis and obstructive intestinal pathology. Laboratory data (elevated serum amylase and lipase levels) and ultrasonography carry out an accurate diagnosis. The management of acute pancreatitis is based on the use of symptomatic drugs, a low fat diet alternated to the parenteral nutrition when triglycerides levels are more than 28 mmol/L. Surgical therapy, used only in case of obstructive pathology of biliary tract, is optimally collected in the third trimester or immediately after postpartum. Our patients, treated only medically, delivered respectively at 38th and 40th week of gestation. Tempestivity of diagnosis and appropriate therapy permit to improve prognosis of a pathology that, although really associated with pregnancy, presents high maternal mortality (37%) cause of complications (shock, coagulopathy, acute respiratory insufficiency) and fetal (37.9%) by occurrence of preterm delivery. PMID:8139793

  20. Pancreatic and peri-pancreatic lesions mimic pancreatic islet cell tumor in multidetector computed tomography

    Institute of Scientific and Technical Information of China (English)

    XUE Hua-dan; LIU Wei; XIAO Yu; SUN Hao; WANG Xuan; LEI Jing; JIN Zheng-yu

    2011-01-01

    Objective This pictorial review aimed to summarize the most possible differential diagnosis of pancreatic islet cell tumor (PICT).Data sources Data used in this review were mainly from Medline and Pubmed in English. And all clinical images in this review were from Department of Radiology, Peking Union Medical College Hospital, Beijing, China.Study selection Cases of pancreatic cystadenoma, solid pseudo-papillary tumor of the pancreas, pancreatic metastasis, pancreatic adenocarcinoma, para-pancreatic neuroendocrine tumors, Castleman disease, gastrointestinal stromal tumor, splenic artery aneurysm and accessory spleen were selected in this pictorial review for differential diagnosis of PICT.Results Careful analysis of imaging features and correlation with the clinical manifestations may allow a more specific diagnosis. It is also important that the radiologist is familiar with the anatomic variants and disease entities which mimic pancreatic islet cell tumor in order to avoid an improper treatment protocol.Conclusions Many congenital anatomic variants or other pancreatic and peri-pancreatic diseases may mimic MDCT appearance of pancreatic islet cell tumor. Radiological, clinical and pathological characteristics should be considered for the final diagnosis.

  1. Diagnosis and treatment of pancreatic pseudocysts in chronic pancreatitis.

    Science.gov (United States)

    Aghdassi, Ali; Mayerle, Julia; Kraft, Matthias; Sielenkämper, Andreas W; Heidecke, Claus-Dieter; Lerch, Markus M

    2008-03-01

    Pancreatic pseudocysts are a well-known complication of acute or chronic pancreatitis, with a higher incidence in the latter. Diagnosis is accomplished most often by computed tomographic scanning, by endoscopic retrograde cholangiopancreatography, or by ultrasound, and a rapid progress in the improvement of diagnostic tools enables detection with high sensitivity and specificity. Different strategies contribute to the treatment of pancreatic pseudocysts: endoscopic transpapillary or transmural drainage, percutaneous catheter drainage, or open surgery. The feasibility of endoscopic drainage is highly dependent on the anatomy and topography of the pseudocyst, but provides high success and low complication rates. Percutaneous drainage is used for infected pseudocysts. However, its usefulness in chronic pancreatitis-associated pseudocysts is questionable. Internal drainage and pseudocyst resection are frequently used as surgical approaches with a good overall outcome, but a somewhat higher morbidity and mortality compared with endoscopic intervention. We therefore conclude that pseudocyst treatment in chronic pancreatitis can be effectively achieved by both endoscopic and surgical means. This review entails publications referring to the classification of pancreatic pseudocysts, epidemiology, diagnostic tools, and therapeutic options for pancreatic pseudocysts. Only full articles were considered for the review. Based on a search in PubMed, the MeSH terms "pancreatic pseudocysts and classification," "diagnosis," and "endoscopic, percutaneous, and surgical treatment" were used either alone or in combination. PMID:18376299

  2. A mouse model of severe acute pancreatitis induced with caerulein and lipopolysaccharide

    Institute of Scientific and Technical Information of China (English)

    Shi-Ping Ding; Ji-Cheng Li; Chang Jin

    2003-01-01

    AIM: To establish a non-traumatic, easy to induce and reproducible mouse model of severe acute pancreatitis (SAP)induced with caerulein and lipopolyasccharide (LPS).METHODS: Thirty-two healthy mature NIH female mice were selected and divided at random into four groups (each of 8 mice), i.e., the control group (NS group), the caerulein group (Ch group), the lipopolysaccharide group (LPS group),and the caerulein+LPS group (Cn+LPS group). Mice were injected intraperitoneally with caerulein only, or LPS only,and caerulein and LPS in combination. All the animals were then killed by neck dislocation three hours after the last intraperitoneal injection. The pancreas and exo-pancreatic organs were then carefully removed for microscopic examination. And the pancreatic acinus was further observed under transmission electron microscope (TEM). Pancreatic weight, serum amylase, serum nitric oxide (NO)concentration, superoxide dismutase (SOD) and malondialdehyde (MDA) concentration of the pancreas were assayed respectively.RESULTS: (1) NS animals displayed normal pancreatic structure both in the exocrine and endocrine. In the LPS group, the pancreas was slightly edematous, with the infiltration of a few inflammatory cells and the necrosis of the adjacent fat tissues. All the animals of the Cn group showed distinct signs of a mild edematous pancreatitis characterized by interstitial edema, infiltration of neutrophil and mononuclear cells, but without obvious parenchyma necrosis and hemorrhage. In contrast, the Cn+LPS groupshowed more diffuse focal areas of nonviable pancreatic and hemorrhage as well as systemic organ dysfunction.According to Schmidt's criteria, the pancreatic histologic score showed that there existed significant difference in the Cn+LPS group in the interstitial edema, inflammatory infiltration,parenchyma necrosis and parenchyma homorrhage in comparison with those of the Cn group, LPS group and NS group (P<0.01 or P<0.05). (2) The ultrasturcture of acinar

  3. Possible Involvement of Pancreatic Fatty Infiltration in Pancreatic Carcinogenesis

    Directory of Open Access Journals (Sweden)

    Mika Hori

    2016-03-01

    Full Text Available Pancreatic cancer is difficult to diagnose in its early stage and is one of the most lethal human cancers. Thus, it is important to clarify its major risk factors, predictive factors and etiology. Here, we focus on fatty infiltration of the pancreas and suggest that it could be a risk factor for pancreatic cancer. Fatty infiltration of the pancreas is observed as ectopic adipocytes infiltrating the pancreatic tissue and is positively correlated with obesity and the prevalence of diabetes mellitus, which are risk factors for pancreatic cancer. However, whether fatty infiltration is a major risk factor for pancreatic cancer has not been established. Recent clinical studies show there is a positive correlation between fatty infiltration of the pancreas and pancreatic precancerous lesions or ductal adenocarcinomas. Animal experimental studies also show an association between fatty infiltration of the pancreas and pancreatic precancerous lesions or ductal adenocarcinomas development. Syrian golden hamsters, which are sensitive to chemical carcinogens in the pancreas, develop fatty infiltration of the pancreas with age. The combination of a high-fat diet and a chemical carcinogen that induces a K-ras mutation increases the severity of fatty infiltration of the pancreas. Thus, fatty infiltration of the pancreas is suggested to promote pancreatic carcinogenesis via a K-ras activating mutation. It is assumed that increased expression of adipokines and of inflammatory and proliferation-associated factors elicited by fatty infiltration of the pancreas may contribute to pancreatic precancerous lesions or ductal adenocarcinomas development. Accumulating evidence suggests that in addition to suppression of Ras activation, methods to modulate fatty infiltration in the pancreas can be considered as a strategy for preventing pancreatic cancer.

  4. Groove pancreatitis: A rare form of chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Bharivi Jani

    2015-01-01

    Full Text Available Context: Groove pancreatitis is a rare form of chronic pancreatitis affecting the "groove" of the pancreas among the pancreatic head, duodenum, and common bile duct. The exact cause is unknown, although there are associations with long-term alcohol abuse, smoking, peptic ulcer disease, heterotopic pancreas, gastric resection, biliary disease, and anatomical or functional obstruction of the minor papilla. The diagnosis can be challenging. Endoscopic ultrasound (EUS and magnetic resonance cholangiopancreatography are the preferred imaging modalities. The treatment of choice is conservative although surgical intervention can sometimes be required. Case Report: A 57-year-old male with a history of human immunodeficiency virus and hepatitis B presented with 4 days of epigastric pain. Abdominal exam revealed absent bowel sounds and epigastric tenderness. He had a creatinine of 1.72 mg/dL, potassium of 2.9 mmol/L, and a normal lipase level of 86 U/L. Liver enzymes and total bilirubin were normal. Computed tomography abdomen showed high-grade obstruction of the second portion of the duodenum without any obvious mass. An esophagogastroduodenoscopy showed a mass at the duodenal bulb causing luminal narrowing, with biopsies negative for malignancy. Magnetic resonance imaging revealed a mass in the region of the pancreatic head and descending duodenum. EUS revealed a 3 cm mass in the region of pancreatic head with irregular borders and no vascular invasion. Fine needle aspiration (FNA was nondiagnostic. The patient then underwent a Whipple′s procedure. Pathology of these specimens was negative for malignancy but was consistent with para-duodenal or groove pancreatitis. Conclusion: The low incidence of groove pancreatitis is partly due to lack of familiarity with the disease. Groove pancreatitis should be considered in the differential for patients presenting with pancreatic head lesions and no cholestatic jaundice, especially when a duodenal obstruction

  5. Molecular characteristics of pancreatic carcinogenesis

    NARCIS (Netherlands)

    Koorstra, J.M.

    2010-01-01

    Ductal adenocarcinoma of the pancreas is a very aggressive disease with a high mortality rate. Pancreatic carcinoma is the fourth leading cause of cancer-related death in Western countries, despite the fact this cancer accounts for only about 3% of all malignant tumors. Most pancreatic cancers (appr

  6. Acute necrotizing pancreatitis in rats

    NARCIS (Netherlands)

    B. van Ooijen (Baan)

    1988-01-01

    textabstractThe specific aim of the present study was to investigate whether eicosanoids play a role in acute necrotizing pancreatitis. Because of the limited number of patients with acute pancreatitis admitted to the hospital each year, as well as the practical difficulties encountered in studying

  7. Pancreatic adenocarcinoma pathology : changing "landscape"

    NARCIS (Netherlands)

    Brosens, Lodewijk A A; Hackeng, Wenzel M; Offerhaus, G Johan; Hruban, Ralph H; Wood, Laura D

    2015-01-01

    Pancreatic cancer is a devastating disease. At time of diagnosis the disease is usually advanced and only a minority of patients are eligible for surgical resection. The overall 5-year survival is 6%. However, survival of patients with early stage pancreatic cancer is significantly better. To improv

  8. Whipple Procedure for Pancreatic Cancer

    Medline Plus

    Full Text Available WHIPPLE PROCEDURE FOR PANCREATIC CANCER UNIVERSITY OF MARYLAND MEDICAL CENTER BALTIMORE, MD January 7, 2008 00:00:11 ANNOUNCER: This year, an estimated 37,000 new cases of pancreatic cancer will be diagnosed in this country. Since there ...

  9. Surgery for pancreatic cancer -- discharge

    Science.gov (United States)

    ... enable JavaScript. Pancreatic surgery is done to treat cancer of the pancreas gland. When You Are in the Hospital All ... Claudius C, Lillemoe KD. Palliative Therapy for Pancreatic Cancer. In: Cameron ... Vickers SM. Exocrine Pancreas. In: Townsend CM Jr, Beauchamp RD, Evers BM, ...

  10. Diet and Pancreatic Cancer Prevention.

    Science.gov (United States)

    Casari, Ilaria; Falasca, Marco

    2015-11-23

    Pancreatic cancer is without any doubt the malignancy with the poorest prognosis and the lowest survival rate. This highly aggressive disease is rarely diagnosed at an early stage and difficult to treat due to its resistance to radiotherapy and chemotherapy. Therefore, there is an urgent need to clarify the causes responsible for pancreatic cancer and to identify preventive strategies to reduce its incidence in the population. Some circumstances, such as smoking habits, being overweight and diabetes, have been identified as potentially predisposing factors to pancreatic cancer, suggesting that diet might play a role. A diet low in fat and sugars, together with a healthy lifestyle, regular exercise, weight reduction and not smoking, may contribute to prevent pancreatic cancer and many other cancer types. In addition, increasing evidence suggests that some food may have chemo preventive properties. Indeed, a high dietary intake of fresh fruit and vegetables has been shown to reduce the risk of developing pancreatic cancer, and recent epidemiological studies have associated nut consumption with a protective effect against it. Therefore, diet could have an impact on the development of pancreatic cancer and further investigations are needed to assess the potential chemo preventive role of specific foods against this disease. This review summarizes the key evidence for the role of dietary habits and their effect on pancreatic cancer and focuses on possible mechanisms for the association between diet and risk of pancreatic cancer.

  11. Diet and Pancreatic Cancer Prevention

    Directory of Open Access Journals (Sweden)

    Ilaria Casari

    2015-11-01

    Full Text Available Pancreatic cancer is without any doubt the malignancy with the poorest prognosis and the lowest survival rate. This highly aggressive disease is rarely diagnosed at an early stage and difficult to treat due to its resistance to radiotherapy and chemotherapy. Therefore, there is an urgent need to clarify the causes responsible for pancreatic cancer and to identify preventive strategies to reduce its incidence in the population. Some circumstances, such as smoking habits, being overweight and diabetes, have been identified as potentially predisposing factors to pancreatic cancer, suggesting that diet might play a role. A diet low in fat and sugars, together with a healthy lifestyle, regular exercise, weight reduction and not smoking, may contribute to prevent pancreatic cancer and many other cancer types. In addition, increasing evidence suggests that some food may have chemo preventive properties. Indeed, a high dietary intake of fresh fruit and vegetables has been shown to reduce the risk of developing pancreatic cancer, and recent epidemiological studies have associated nut consumption with a protective effect against it. Therefore, diet could have an impact on the development of pancreatic cancer and further investigations are needed to assess the potential chemo preventive role of specific foods against this disease. This review summarizes the key evidence for the role of dietary habits and their effect on pancreatic cancer and focuses on possible mechanisms for the association between diet and risk of pancreatic cancer.

  12. Pathologic pancreatic endocrine cell hyperplasia

    Institute of Scientific and Technical Information of China (English)

    Debra Ouyang; Deepti Dhall; Run Yu

    2011-01-01

    Pathologic hyperplasia of various pancreatic endocrine cells is rare but has been long known. β cell hyperplasia contributes to persistent hyperinsulinemic hypoglycemia of infancy, which is commonly caused by mutations in the islet ATP-sensitive potassium channel, and to noninsulinoma pancreatogenous hypoglycemia in adults,which may or may not be associated with bariatric surgery.α cell hyperplasia may cause glucagonoma syndrome or induce pancreatic neuroendocrine tumors. An inactivating mutation of the glucagon receptor causes α cell hyperplasia and asymptomatic hyperglucagonemia.Pancreatic polypeptide cell hyperplasia has been described without a clearly-characterized clinical syndrome and hyperplasia of other endocrine cells inside the pancreas has not been reported to our knowledge.Based on morphological evidence, the main pathogenetic mechanism for pancreatic endocrine cell hyperplasia is increased endocrine cell neogenesis from exocrine ductal epithelium. Pancreatic endocrine cell hyperplasia should be considered in the diagnosis and management of hypoglycemia, elevated islet hormone levels,and pancreatic neuroendocrine tumors. Further studies of pathologic pancreatic endocrine cell hyperplasia will likely yield insights into the pathogenesis and treatment of diabetes and pancreatic neuroendocrine tumors.

  13. Acute pancreatitis after a course of clarithromycin.

    NARCIS (Netherlands)

    Schouwenberg, B.J.J.W.; Deinum, J.

    2003-01-01

    We present a case of acute pancreatitis after a course of clarithromycin. An 84-year-old woman died of suspected pneumonia and cardiac failure. Autopsy surprisingly revealed acute pancreatitis. Except for the use of clarithromycin no other cause for her acute pancreatitis was obvious. Pancreatitis i

  14. What difference exists in the pancreas of mammals with sanguivorous diet? A morphological, stereological and immunohistochemical study of the pancreatic islets of the hematophagous bat Diphylla ecaudata.

    Science.gov (United States)

    Machado-Santos, Clarice; Aquino, Júlio César Fraulob; Mikalauka, Jefferson Simanas; Abidu-Figueiredo, Marcelo; Mendes, Rosa Maria Marcos; Sales, Armando

    2013-05-10

    Diphylla ecaudata is a vampire bat that mainly feeds on the blood of birds. This highly specialized diet - hematophagy - is accompanied by a series of morphological changes in the gastro-entero-pancreatic system, since the distribution and relative proportions of different pancreatic endocrine cell types can vary between species due to different physiological conditions and eating habits. The aim of this study was to examine for the first time the pancreas of the vampire bat D. ecaudata using morphological, stereological and immunohistochemical techniques. The pancreas of the D. ecaudata has an exocrine acinar portion in which the highest concentration of pancreatic islets is scattered. These pancreatic islets have irregular size and a mean diameter of 56.94 μm. The total number of islets in the pancreas was 23,900, with a volumetric density of 4.1%. Insulin-immunoreactive (IR) cells were located in the central pancreatic islet region and had the largest density (54.8%). Glucagon-IR cells were located mainly in the peripheral mantle region (16.2%), along with somatostatin-IR (SS) cells (14.3%). Cells immunoreactive to insulin, glucagon and somatostatin were also observed to have spread in isolated places in the exocrine pancreas. In the connective tissue near the pancreatic ducts, a high concentration was identified of insulin-IR cells and a low concentration of glucagon-IR and somatostatin-IR cells. These results indicate that although the pancreas of D. ecaudata has morphological similarities with that of other mammals, it has a differentiated islet structure, because there were a large number of islets and different volumetric densities of α, β and δ cells. PMID:23500834

  15. Enteral feeding without pancreatic stimulation

    DEFF Research Database (Denmark)

    Kaushik, Neeraj; Pietraszewski, Marie; Holst, Jens Juul;

    2005-01-01

    OBJECTIVE: All forms of commonly practiced enteral feeding techniques stimulate pancreatic secretion, and only intravenous feeding avoids it. In this study, we explored the possibility of more distal enteral infusions of tube feeds to see whether activation of the ileal brake mechanism can result...... in enteral feeding without pancreatic stimulation, with particular reference to trypsin, because the avoidance of trypsin stimulation may optimize enteral feeding in acute pancreatitis. METHODS: The pancreatic secretory responses to feeding were studied in 36 healthy volunteers by standard double...... in plasma glucagon-like peptide-1 and peptide YY concentrations. CONCLUSIONS: Our results suggest that enteral feeding can be given without stimulating pancreatic trypsin secretion provided it is delivered into the mid-distal jejunum. The mechanism may involve activation of the ileal brake mechanism....

  16. Pharmacological challenges in chronic pancreatitis

    DEFF Research Database (Denmark)

    Olesen, Anne Estrup; Brokjaer, Anne; Fischer, Iben Wendelboe Deleuran;

    2014-01-01

    Drug absorption in patients with chronic pancreatitis might be affected by the pathophysiology of the disease. The exocrine pancreatic insufficiency is associated with changes in gastrointestinal intraluminal pH, motility disorder, bacterial overgrowth and changed pancreatic gland secretion....... Together these factors can result in malabsorption and may also affect the efficacy of pharmacological intervention. The lifestyle of chronic pancreatitis patients may also contribute to gastrointestinal changes. Many patients limit their food intake because of the pain caused by eating and in some cases...... food intake is more or less substituted with alcohol, tobacco and coffee. Alcohol and drug interaction are known to influence the pharmacokinetics by altering either drug absorption or by affecting liver metabolism. Since patients suffering from chronic pancreatitis experience severe pain, opioids...

  17. Roles of AQP5/AQP5-G103D in carbamylcholine-induced volume decrease and in reduction of the activation energy for water transport by rat parotid acinar cells.

    Science.gov (United States)

    Satoh, Keitaro; Seo, Yoshiteru; Matsuo, Shinsuke; Karabasil, Mileva Ratko; Matsuki-Fukushima, Miwako; Nakahari, Takashi; Hosoi, Kazuo

    2012-10-01

    In order to assess the contribution of the water channel aquaporin-5 (AQP5) to water transport by salivary gland acinar cells, we measured the cell volume and activation energy (E (a)) of diffusive water permeability in isolated parotid acinar cells obtained from AQP5-G103D mutant and their wild-type rats. Immunohistochemistry showed that there was no change induced by carbamylcholine (CCh; 1 μM) in the AQP5 detected in the acinar cells in the wild-type rat. Acinar cells from mutant rats, producing low levels of AQP5 in the apical membrane, showed a minimal increase in the AQP5 due to the CCh. In the wild-type rat, CCh caused a transient swelling of the acinus, followed by a rapid agonist-induced cell shrinkage, reaching a plateau at 30 s. In the mutant rat, the acinus did not swell by CCh challenge, and the agonist-induced cell shrinkage was delayed by 8 s, reaching a transient minimum at around 1 min, and recovered spontaneously even though CCh was persistently present. In the unstimulated wild-type acinar cells, E (a) was 3.4 ± 0.6 kcal mol(-1) and showed no detectable change after CCh stimulation. In the unstimulated mutant acinar cells, high E (a) value (5.9 ± 0.1 kcal mol(-1)) was detected and showed a minimal decrease after CCh stimulation (5.0 ± 0.3 kcal mol(-1)). These results suggested that AQP5 was the main pathway for water transport in the acinar cells and that it was responsible for the rapid agonist-induced acinar cell shrinkage and also necessary to keep the acinar cell volume reduced during the steady secretion in the wild-type rat.

  18. [Prolonged acute pancreatitis after bone marrow transplantation].

    Science.gov (United States)

    De Singly, B; Simon, M; Bennani, J; Wittnebel, S; Zagadanski, A-M; Pacault, V; Gornet, J-M; Allez, M; Lémann, M

    2008-04-01

    Acute pancreatitis is not infrequent after allogenic marrow transplantation. Several causes can predispose to pancreatitis, including Graft-Versus-Host Disease (GVHD), a condition which is probably underestimated. In the literature, few description of pancreatic GVHD can be found. Pancreatic GVHD diagnosis can be difficult if pancreatic involvement occurs without other typical manifestations of GVHD. We report the case of a woman, 54 years old, suffering from prolonged, painful pancreatitis two months after allogenic bone marrow transplantation for acute myeloid leucemia. Pancreatic GVHD diagnosis was performed after five weeks on duodenal biopsies despite the absence of diarrheoa. The patient dramatically improved within few days on corticosteroids.

  19. Ae4 (Slc4a9) Anion Exchanger Drives Cl- Uptake-dependent Fluid Secretion by Mouse Submandibular Gland Acinar Cells.

    Science.gov (United States)

    Peña-Münzenmayer, Gaspar; Catalán, Marcelo A; Kondo, Yusuke; Jaramillo, Yasna; Liu, Frances; Shull, Gary E; Melvin, James E

    2015-04-24

    Transcellular Cl(-) movement across acinar cells is the rate-limiting step for salivary gland fluid secretion. Basolateral Nkcc1 Na(+)-K(+)-2Cl(-) cotransporters play a critical role in fluid secretion by promoting the intracellular accumulation of Cl(-) above its equilibrium potential. However, salivation is only partially abolished in the absence of Nkcc1 cotransporter activity, suggesting that another Cl(-) uptake pathway concentrates Cl(-) ions in acinar cells. To identify alternative molecular mechanisms, we studied mice lacking Ae2 and Ae4 Cl(-)/HCO3 (-) exchangers. We found that salivation stimulated by muscarinic and β-adrenergic receptor agonists was normal in the submandibular glands of Ae2(-/-) mice. In contrast, saliva secretion was reduced by 35% in Ae4(-/-) mice. The decrease in salivation was not related to loss of Na(+)-K(+)-2Cl(-) cotransporter or Na(+)/H(+) exchanger activity in Ae4(-/-) mice but correlated with reduced Cl(-) uptake during β-adrenergic receptor activation of cAMP signaling. Direct measurements of Cl(-)/HCO3 (-) exchanger activity revealed that HCO3 (-)-dependent Cl(-) uptake was reduced in the acinar cells of Ae2(-/-) and Ae4(-/-) mice. Moreover, Cl(-)/HCO3 (-) exchanger activity was nearly abolished in double Ae4/Ae2 knock-out mice, suggesting that most of the Cl(-)/HCO3 (-) exchanger activity in submandibular acinar cells depends on Ae2 and Ae4 expression. In conclusion, both Ae2 and Ae4 anion exchangers are functionally expressed in submandibular acinar cells; however, only Ae4 expression appears to be important for cAMP-dependent regulation of fluid secretion.

  20. Mouse models of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Marta Herreros-Villanueva; Elizabeth Hijona; Angel Cosme; Luis Bujanda

    2012-01-01

    Pancreatic cancer is one of the most lethal of human malignancies ranking 4th among cancer-related death in the western world and in the United States,and potent therapeutic options are lacking.Although during the last few years there have been important advances in the understanding of the molecular events responsible for the development of pancreatic cancer,currently specific mechanisms of treatment resistance remain poorly understood and new effective systemic drugs need to be developed and probed.In vivo models to study pancreatic cancer and approach this issue remain limited and present different molecular features that must be considered in the studies depending on the purpose to fit special research themes.In the last few years,several genetically engineered mouse models of pancreatic exocrine neoplasia have been developed.These models mimic the disease as they reproduce genetic alterations implicated in the progression of pancreatic cancer.Genetic alterations such as activating mutations in KRas,or TGFb and/or inactivation of tumoral suppressors such as p53,INK4A/ARF BRCA2 and Smad4 are the most common drivers to pancreatic carcinogenesis and have been used to create transgenic mice.These mouse models have a spectrum of pathologic changes,from pancreatic intraepithelial neoplasia to lesions that progress histologically culminating in fully invasive and metastatic disease and represent the most useful preclinical model system.These models can characterize the cellular and molecular pathology of pancreatic neoplasia and cancer and constitute the best tool to investigate new therapeutic approaches,chemopreventive and/or anticancer treatments.Here,we review and update the current mouse models that reproduce different stages of human pancreatic ductal adenocarcinoma and will have clinical relevance in future pancreatic cancer developments.

  1. Individual susceptibility to alcoholic pancreatitis.

    Science.gov (United States)

    Apte, Minoti V; Pirola, Romano C; Wilson, Jeremy S

    2008-03-01

    The observation that only a minority of heavy drinkers develop pancreatitis has prompted an intensive search for a trigger factor/cofactor/susceptibility factor that may precipitate a clinical attack. Putative susceptibility factors examined so far include diet, smoking, amount and type of alcohol consumed, the pattern of drinking and lipid intolerance. In addition, a range of inherited factors have been assessed including blood group antigens, human leukocyte antigen serotypes, alpha-1-antitrypsin phenotypes and several genotypes. The latter group comprises mutations/polymorphisms in genes related to alcohol-metabolizing enzymes, detoxifying enzymes, pancreatic digestive enzymes, pancreatic enzyme inhibitors, cystic fibrosis and cytokines. Disappointingly, despite this concerted research effort, no clear association has been established between the above factors and alcoholic pancreatitis. Experimentally, the secretagogue cholecystokinin (CCK) has been investigated as a candidate 'trigger' for alcoholic pancreatitis. However, the clinical relevance of CCK as a trigger factor has to be questioned, as it is difficult to envisage a situation in humans where abnormally high levels of CCK would be released into the circulation to trigger pancreatitis in alcoholics. In contrast, bacterial endotoxemia is a candidate cofactor that does have relevance to the clinical situation. Plasma lipopolysaccharide (LPS, an endotoxin) levels are significantly higher in drinkers (either after chronic alcohol intake or a single binge) compared to non-drinkers. We have recently shown that alcohol-fed animals challenged with otherwise innocuous doses of LPS exhibit significant pancreatic injury. Moreover, repeated LPS exposure in alcohol-fed rats leads to progressive injury to the gland characterized by significant pancreatic fibrosis. These studies support the concept that endotoxin may be an important factor in the initiation and progression of alcoholic pancreatitis. Scope remains for

  2. Targeting of the P2X7 receptor in pancreatic cancer and stellate cells.

    Science.gov (United States)

    Giannuzzo, Andrea; Saccomano, Mara; Napp, Joanna; Ellegaard, Maria; Alves, Frauke; Novak, Ivana

    2016-12-01

    The ATP-gated receptor P2X7 (P2X7R) is involved in regulation of cell survival and has been of interest in cancer field. Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer and new markers and therapeutic targets are needed. PDAC is characterized by a complex tumour microenvironment, which includes cancer and pancreatic stellate cells (PSCs), and potentially high nucleotide/side turnover. Our aim was to determine P2X7R expression and function in human pancreatic cancer cells in vitro as well as to perform in vivo efficacy study applying P2X7R inhibitor in an orthotopic xenograft mouse model of PDAC. In the in vitro studies we show that human PDAC cells with luciferase gene (PancTu-1 Luc cells) express high levels of P2X7R protein. Allosteric P2X7R antagonist AZ10606120 inhibited cell proliferation in basal conditions, indicating that P2X7R was tonically active. Extracellular ATP and BzATP, to which the P2X7R is more sensitive, further affected cell survival and confirmed complex functionality of P2X7R. PancTu-1 Luc migration and invasion was reduced by AZ10606120, and it was stimulated by PSCs, but not by PSCs from P2X7(-/-) animals. PancTu-1 Luc cells were orthotopically transplanted into nude mice and tumour growth was followed noninvasively by bioluminescence imaging. AZ10606120-treated mice showed reduced bioluminescence compared to saline-treated mice. Immunohistochemical analysis confirmed P2X7R expression in cancer and PSC cells, and in metaplastic/neoplastic acinar and duct structures. PSCs number/activity and collagen deposition was reduced in AZ10606120-treated tumours. PMID:27513892

  3. Characterization of the bombesin receptor on mouse pancreatic acini by chemical cross-linking

    Energy Technology Data Exchange (ETDEWEB)

    Huang, S.C.; Yu, D.H.; Wank, S.A.; Gardner, J.D.; Jensen, R.T. (National Institutes of Health, Bethesda, MD (USA))

    1990-11-01

    Bombesin (BN), gastrin-releasing peptide (GRP) and GRP(18-27) (neuromedin C) were equipotent and 30-fold more potent than neuromedin B (NMB) in inhibiting binding of {sup 125}I-GRP to and in stimulating amylase release from mouse pancreatic acini. In the present study we used {sup 125}I-GRP and chemical cross-linking techniques to characterize the mouse pancreatic BN receptor. After binding of {sup 125}I-GRP to membranes, and incubation with various chemical cross-linking agents, cross-linked radioactivity was analyzed by SDS-PAG electrophoresis and autoradiography. With each of 4 different chemical cross-linking agents, there was a single broad polypeptide band of Mr 80,000. Cross-linking did not occur in the absence of the cross-linking agent. Cross-linking was inhibited only by peptides that interact with the BN receptor such as GRP, NMB, GRP(18-27) or BN. Dose-inhibition curves for the ability of BN or NMB to inhibit binding of {sup 125}I-GRP to membranes or cross-linking to the 80,000 polypeptide demonstrated for both that BN was 15-fold more potent than NMB. The apparent molecular weight of the cross-linked polypeptide was unchanged by adding dithiothreitol. N-Glycanase treatment reduced the molecular weight of the cross-linked peptide to 40,000. The present results indicate that the BN receptor on mouse pancreatic acinar cell membranes resembles that recently described on various tumor cells in being a single glycoprotein with a molecular weight of 76,000. Because dithiothreitol had no effect, this glycoprotein is not a subunit of a larger disulfide-linked structure.

  4. Pancreatic microcirculatory impairment in experimental acute pancreatitis in rats

    Institute of Scientific and Technical Information of China (English)

    Zong-Guang Zhou; You-Dai Chen; Wei Sun; Zhong Chen

    2002-01-01

    AIM: To study the feature of pancreatic microcirculatoryimpairment, especially the initial changes, in caerulein-induced experimental acute pancreatitis (AP).METHODS: The pancreatic microcirculation of caerulein-induced AP model was studied by intravital fluorescencemicroscopy with FITC-labeled erythrocytes (FITC-RBC),scanning electron microscopy of vascular corrosion casts,and light microscopy of Chinese ink-injected/cleared tissues.RESULTS: Animals in caerulein-treated group showedhyperamylemia (× 2), pancreatic oedema, infiltration ofinflammatory cells in pancreas. Constrictions of intralobulararteriolar sphincters, presence of vacuoles in all layers ofsphincter, and gross irregularity in capillary network of aciniwere found in the AP specimens. The decrease of pancreaticcapillary blood flow (0.34±0.10 nl @ min-1 vs0.910.06 nl @rain-1 of control, P<0.001), reduction of functional capillarydensity(277± 13 cm-1 vs349±8 cm-1 of control, P<0.001),and irregular intermittent perfusion were observed incaerulein-induced groups.CONCLUSION: Impairment and constriction of pancreaticintralobular arteriolar sphincter are the initial microcirculatorylesions in the early phase of acute pancreatitis, and play akey role in the pancreatic ischaemia and pancreaticmicrovascular failure in acute pancreatitis.

  5. Evaluation of pancreatic scintigram in the diagnosis of pancreatic diseases

    International Nuclear Information System (INIS)

    The classification of accumulative patterns with the pancreatic scintigram findings of chronic pancreatitis and carcinoma of the pancreas were compared with endoscopic retrograde pancreatography (ERP) findings and Pancreozymin-Secretin test (P-S test). I) The frequency of pancreatic cancer was 93%, whilst, the chronic pancreatitis was 88% in the abnormal pancreatic scintigram. II) In the scintigram the type II (localyzed defect shadows) of pancreatic cancer was comparatively high and it is proportional to evidence. derived from ERP. Localized diagnostic certainty is helpful, although the two tests are related. The P-S test is only restricted to the carcinoma of head, whilst, scintigram is more useful to detect the carcinoma of the body and tail of the pancreas. III) As for the chronic pancreatitis, there are various accumulative patterns. This is resemblance to that of ERP findings, but in the P-S normal test, it showed discrepancy in part of the result. Particularly, in the type I (slightly generalized low uptake with density silhouette) and type II. Therefore in order to obtain an accurate diagnosis, it is essential to have both the P-S test and scintigram. (author)

  6. Dexamethasone mediates protection against acute pancreatitis via upregulation of pancreatitis-associated proteins

    OpenAIRE

    Kandil, Emad; Lin, Yin-yao; Bluth, Martin H; Zhang, Hong; Levi, Gabriel; Zenilman, Michael E

    2006-01-01

    AIM: To examine the influence of dexamethasone on pancreatitis-associated protein (PAP) gene expression using both in vitro and in vivo models of acute pancreatitis and to study how PAP gene expression correlates with severity of pancreatitis.

  7. Is acute recurrent pancreatitis a chronic disease?

    OpenAIRE

    Mariani, Alberto; Testoni, Pier Alberto

    2008-01-01

    Whether acute recurrent pancreatitis is a chronic disease is still debated and a consensus is not still reached as demonstrated by differences in the classification of acute recurrent pancreatitis. There is major evidence for considering alcoholic pancreatitis as a chronic disease ab initio while chronic pancreatitis lesions detectable in biliary acute recurrent pancreatitis (ARP) seem a casual association. Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutation, hereditary a...

  8. Imaging in the diagnosis of chronic pancreatitis

    OpenAIRE

    Vasile D. Balaban; Andrei M. Lungu; Dragoș Cuzino; Săndica Bucurică; Bogdan Macadon; Mihăiță Pătrășescu; Raluca S. Costache; Petruț Nuță; Constantin Ştefani; Florentina Ioniță-Radu; Mariana Jinga

    2014-01-01

    Chronic pancreatitis is characterised by progressive and irreversible damage of the pancreatic parenchyma and ductal system, which leads to chronic pain, loss of endocrine and exocrine functions. Clinically, pancreatic exocrine insufficiency becomes apparent only after 90% of the parenchima has been lost. Despite the simple definition, diagnosing chronic pancreatitis remains a challenge, especially for early stage disease. Because pancreatic function tests can be normal until l...

  9. Detecting Early Pancreatic Cancer- Problems and Prospects

    OpenAIRE

    Chari, Suresh T.

    2007-01-01

    Pancreatic cancer has a poor prognosis. Improving survival will require diagnosis of early pancreatic cancer which can be defined based on resectability, size or curability. Pancreatic cancer progresses from non-invasive precursor lesions to invasive cancer over a variable time period. Retrospective review of CT scans done prior to diagnosis suggests that pancreatic cancer resectability may be significantly improved if detected as few as 6 months before clinical diagnosis. Since pancreatic ca...

  10. Contrast-enhanced sonography in pancreatic diseases

    Energy Technology Data Exchange (ETDEWEB)

    Rickes, Steffen [Department of Internal Medicine, AMEOS Hospital GmbH, Halberstadt (Germany); Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University, Magdeburg (Germany)], E-mail: rickes@medkl.salvator-kh.de; Rauh, Peter; Uhle, Christine; Ensberg, Daniel [Department of Internal Medicine, AMEOS Hospital GmbH, Halberstadt (Germany); Moenkemueller, Klaus; Malfertheiner, Peter [Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke-University, Magdeburg (Germany)

    2007-11-15

    Contrast-enhanced sonography is a widely available imaging modality for the diagnosis of pancreatic diseases. With this procedure, pancreatic tumours can be differentiated better. Furthermore, contrast-enhanced sonography produces good results in the staging of acute pancreatitis severity, especially in the detection of pancreatic necrosis. In this review article the value of contrast-enhanced sonography in the diagnosis of pancreatic diseases will be described and discussed.

  11. Alcoholic pancreatitis:Lessons from the liver

    Institute of Scientific and Technical Information of China (English)

    Dahn; L; Clemens; Katrina; J; Mahan

    2010-01-01

    The association between alcohol consumption and pancreatitis has been recognized for over 100 years. Despite the fact that this association is well recognized, the mechanisms by which alcohol abuse leads to pancreatic tissue damage are not entirely clear. Alcohol abuse is the major factor associated with pancreatitis in the Western world. Interestingly, although most cases of chronic pancreatitis and many cases of acute pancreatitis are associated with alcohol abuse, only a small percentage of individuals w...

  12. Cancer Stem Cells in Pancreatic Cancer

    International Nuclear Information System (INIS)

    Pancreatic cancer is an aggressive malignant solid tumor well-known by early metastasis, local invasion, resistance to standard chemo- and radiotherapy and poor prognosis. Increasing evidence indicates that pancreatic cancer is initiated and propagated by cancer stem cells (CSCs). Here we review the current research results regarding CSCs in pancreatic cancer and discuss the different markers identifying pancreatic CSCs. This review will focus on metastasis, microRNA regulation and anti-CSC therapy in pancreatic cancer

  13. 14.2.Pancreatitis

    Institute of Scientific and Technical Information of China (English)

    1993-01-01

    930325 A clinical study on a lipid—based sys-tem of parenteral nutrition in acute pancreati-tis.ZHU Jiangfan (朱江帆),et al.Dept Hepato-bill Surg,lst Teach Hosp,3rd Milit Med Coll.Chin J Digest 1992;12(4):195—197.A controlled prospective study on a lipid-based system of parenteral nutrition has beencarried out in patients with acute pancreatitis.The results show that the patients’ positive ni-trogen balance can be obtained and the visceralproteins can be maintained within normal range

  14. Metronidazole-induced pancreatitis.

    LENUS (Irish Health Repository)

    O'Halloran, E

    2010-01-01

    A 25-year-old caucasian lady presented to the Accident & Emergency department complaining of acute onset severe epigastric pain radiating through to the back with associated nausea and vomiting. A diagnosis of acute pancreatitis was made. Symptoms commenced after the third dose of Metronidazole therapy prescribed for a recurrent periodontal abscess. The patient described a similar episode 10 months previously. On neither occasion were any other medications being taken, there was no history of alcohol abuse and no other gastro-intestinal aetiology could be identified on imaging. Symptoms resolved quickly upon discontinuation of the antibiotic agent. We conclude therefore that Metronidazole can reasonably be identified as the only potential causative agent.

  15. Pancreatic islet transplantation

    Directory of Open Access Journals (Sweden)

    Corrêa-Giannella Maria

    2009-09-01

    Full Text Available Abstract Background No formulation of exogenous insulin available to date has yet been able to mimic the physiological nictemeral rhythms of this hormone, and despite all engineering advancements, the theoretical proposal of developing a mechanical replacement for pancreatic β cell still has not been reached. Thus, the replacement of β cells through pancreas and pancreatic islet transplantation are the only concrete alternatives for re-establishing the endogenous insulin secretion in type 1 diabetic patients. Since only 1 to 1.5% of the pancreatic mass corresponds to endocrine tissue, pancreatic islets transplantation arises as a natural alternative. Data from the International Islet Transplant Registry (ITR from 1983 to December 2000 document a total of 493 transplants performed around the world, with progressively worse rates of post-transplant insulin independence. In 2000, the "Edmonton Protocol" introduced several modifications to the transplantation procedure, such as the use of a steroid-free immunosuppression regimen and transplantation of a mean islet mass of 11,000 islet equivalents per kilogram, which significantly improved 1-year outcomes. Although the results of a 5-year follow-up in 65 patients demonstrated improvement in glycemic instability in a significant portion of them, only 7.5% of the patients have reached insulin independence, indicating the need of further advances in the preservation of the function of transplanted islet. In addition to the scarcity of organs available for transplantation, islets transplantation still faces major challenges, specially those related to cell loss during the process of islet isolation and the losses related to the graft site, apoptosis, allorejection, autoimmunity, and immunosuppression. The main strategies to optimize islet transplantation aim at improving all these aspects. Conclusion Human islet transplantation should be regarded as an intervention that can decrease the frequency of

  16. Screening for Pancreatic Cancer.

    Science.gov (United States)

    Wada, Keita; Takaori, Kyoichi; Traverso, L William

    2015-10-01

    Neither extended surgery nor extended indication for surgery has improved survival in patients with pancreatic cancer. According to autopsy studies, presumably 90% are metastatic. The only cure is complete removal of the tumor at an early stage before it becomes a systemic disease or becomes invasive. Early detection and screening of individuals at risk is currently under way. This article reviews the evidence and methods for screening, either familial or sporadic. Indication for early-stage surgery and precursors are discussed. Surgeons should be familiar with screening because it may provide patients with a chance for cure by surgical resection.

  17. Clinical Impact of the KL-6 Concentration of Pancreatic Juice for Diagnosing Pancreatic Masses

    OpenAIRE

    Kazuya Matsumoto; Yohei Takeda; Kenichi Harada; Takumi Onoyama; Soichiro Kawata; Yasushi Horie; Teruhisa Sakamoto; Masaru Ueki; Norimasa Miura; Yoshikazu Murawaki

    2015-01-01

    Background and Aim. Pancreatic juice cytology (PJC) is considered optimal for differentially diagnosing pancreatic masses, but the accuracy of PJC ranges from 46.7% to 93.0%. The aim of this study was to evaluate the clinical impact of measuring the KL-6 concentration of pancreatic juice for diagnosing pancreatic masses. Methods. PJC and the KL-6 concentration measurements of pancreatic juice were performed for 70 consecutive patients with pancreatic masses (39 malignancies and 31 benign). Re...

  18. Is Zinc Concentration in Pancreatic Fluid a Marker for Pancreatic Diseases?

    OpenAIRE

    Surakit Pungpapong; James S Scolapio; Timothy A. Woodward; Wallace, Michael B.; Massimo Raimondo

    2005-01-01

    Objectives An imbalance of free radicals and scavenging processes has been implicated in the pathogenesis of pancreatic tissue injury. Gradual decreases in antioxidant enzyme expression in pancreatic cells from normal pancreas to chronic pancreatitis to pancreatic cancer have been reported. Zinc is one of the components of antioxidant enzymes and may play a role in the pathogenesis of pancreatic diseases. A recent report showed a significant decrease in pancreatic zinc output in patients with...

  19. Update on Endoscopic Management of Main Pancreatic Duct Stones in Chronic Calcific Pancreatitis

    OpenAIRE

    Choi, Eun Kwang; Lehman, Glen A.

    2012-01-01

    Pancreatic duct stones are a common complication during the natural course of chronic pancreatitis and often contribute to additional pain and pancreatitis. Abdominal pain, one of the major symptoms of chronic pancreatitis, is believed to be caused in part by obstruction of the pancreatic duct system (by stones or strictures) resulting in increasing intraductal pressure and parenchymal ischemia. Pancreatic stones can be managed by surgery, endoscopy, or extracorporeal shock wave lithotripsy. ...

  20. Activation of Pancreatic Stellate Cells in Human and Experimental Pancreatic Fibrosis

    OpenAIRE

    Haber, Paul S; Keogh, Gregory W.; Apte, Minoti V.; Moran, Corey S.; Stewart, Nancy L.; Crawford, Darrell H.G.; Pirola, Romano C.; McCaughan, Geoffrey W.; Ramm, Grant A; Wilson, Jeremy S.

    1999-01-01

    The mechanisms of pancreatic fibrosis are poorly understood. In the liver, stellate cells play an important role in fibrogenesis. Similar cells have recently been isolated from the pancreas and are termed pancreatic stellate cells. The aim of this study was to determine whether pancreatic stellate cell activation occurs during experimental and human pancreatic fibrosis. Pancreatic fibrosis was induced in rats (n = 24) by infusion of trinitrobenzene sulfonic acid (TNBS) into the pancreatic duc...

  1. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Nandy, Debashis; Mukhopadhyay, Debabrata, E-mail: mukhopadhyay.debabrata@mayo.edu [Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, 200 First Street SW, Guggenheim 1321C, Rochester, MN 55905 (United States)

    2011-02-24

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

  2. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    International Nuclear Information System (INIS)

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed

  3. Human salivary gland acinar cells spontaneously form three-dimensional structures and change the protein expression patterns.

    Science.gov (United States)

    Chan, Yen-Hui; Huang, Tsung-Wei; Young, Tai-Horng; Lou, Pei-Jen

    2011-11-01

    Applying tissue engineering principles to design an auto-secretory device is a potential solution for patients suffering loss of salivary gland function. However, the largest challenge in implementing this solution is the primary culture of human salivary gland cells, because the cells are highly differentiated and difficult to expand in vitro. This situation leads to the lack of reports on the in vitro cell biology and physiology of human salivary gland cells. This study used a low-calcium culture system to selectively cultivate human parotid gland acinar (PGAC) cells from tissues with high purity in cell composition. This condition enables PGAC cells to continuously proliferate and retain the phenotypes of epithelial acinar cells to express secreting products (α-amylase) and function-related proteins (aquaporin-3, aquaporin-5, and ZO-1). Notably, when the cells reached confluence, three-dimensional (3D) cell aggregates were observed in crowded regions. These self-formed cell spheres were termed post-confluence structures (PCSs). Unexpectedly, despite being cultured in the same media, cells in PCSs exhibited higher expression levels and different expression patterns of function-related proteins compared to the two-dimensional (2D) cells. Translocation of aquoporin-3 from cytosolic to alongside the cell boundaries, and of ZO-1 molecules to the boundary of the PCSs were also observed. These observations suggest that when PGAC cells cultured on the 2D substrate would form PCSs without the help of 3D scaffolds and retain certain differentiation and polarity. This phenomenon implies that it is possible to introduce 2D substrates instead of 3D scaffolds into artificial salivary gland tissue engineering.

  4. Postnatal Pancreas of Mice Contains Tripotent Progenitors Capable of Giving Rise to Duct, Acinar, and Endocrine Cells In Vitro.

    Science.gov (United States)

    Ghazalli, Nadiah; Mahdavi, Alborz; Feng, Tao; Jin, Liang; Kozlowski, Mark T; Hsu, Jasper; Riggs, Arthur D; Tirrell, David A; Ku, H Teresa

    2015-09-01

    Postnatal pancreas is a potential source for progenitor cells to generate endocrine β-cells for treating type 1 diabetes. However, it remains unclear whether young (1-week-old) pancreas harbors multipotent progenitors capable of differentiating into duct, acinar, and endocrine cells. Laminin is an extracellular matrix (ECM) protein important for β-cells' survival and function. We established an artificial extracellular matrix (aECM) protein that contains the functional IKVAV (Ile-Lys-Val-Ala-Val) sequence derived from laminin (designated aECM-lam). Whether IKVAV is necessary for endocrine differentiation in vitro is unknown. To answer these questions, we cultured single cells from 1-week-old pancreas in semi-solid media supplemented with aECM-lam, aECM-scr (which contains a scrambled sequence instead of IKVAV), or Matrigel. We found that colonies were generated in all materials. Individual colonies were examined by microfluidic reverse transcription-polymerase chain reaction, immunostaining, and electron microscopy analyses. The majority of the colonies expressed markers for endocrine, acinar, and ductal lineages, demonstrating tri-lineage potential of individual colony-forming progenitors. Colonies grown in aECM-lam expressed higher levels of endocrine markers Insulin1, Insulin2, and Glucagon compared with those grown in aECM-scr and Matrigel, indicating that the IKVAV sequence enhances endocrine differentiation. In contrast, Matrigel was inhibitory for endocrine gene expression. Colonies grown in aECM-lam displayed the hallmarks of functional β-cells: mature insulin granules and glucose-stimulated insulin secretion. Colony-forming progenitors were enriched in the CD133(high) fraction and among 230 micro-manipulated single CD133(high) cells, four gave rise to colonies that expressed tri-lineage markers. We conclude that young postnatal pancreas contains multipotent progenitor cells and that aECM-lam promotes differentiation of β-like cells in vitro. PMID

  5. Redox signaling in acute pancreatitis.

    Science.gov (United States)

    Pérez, Salvador; Pereda, Javier; Sabater, Luis; Sastre, Juan

    2015-08-01

    Acute pancreatitis is an inflammatory process of the pancreatic gland that eventually may lead to a severe systemic inflammatory response. A key event in pancreatic damage is the intracellular activation of NF-κB and zymogens, involving also calcium, cathepsins, pH disorders, autophagy, and cell death, particularly necrosis. This review focuses on the new role of redox signaling in acute pancreatitis. Oxidative stress and redox status are involved in the onset of acute pancreatitis and also in the development of the systemic inflammatory response, being glutathione depletion, xanthine oxidase activation, and thiol oxidation in proteins critical features of the disease in the pancreas. On the other hand, the release of extracellular hemoglobin into the circulation from the ascitic fluid in severe necrotizing pancreatitis enhances lipid peroxidation in plasma and the inflammatory infiltrate into the lung and up-regulates the HIF-VEGF pathway, contributing to the systemic inflammatory response. Therefore, redox signaling and oxidative stress contribute to the local and systemic inflammatory response during acute pancreatitis.

  6. Molecular biology of pancreatic cancer

    Institute of Scientific and Technical Information of China (English)

    Miroslav Zavoral; Petra Minarikova; Filip Zavada; Cyril Salek; Marek Minarik

    2011-01-01

    In spite of continuous research efforts directed at early detection and treatment of pancreatic cancer, the outlook for patients affected by the disease remains dismal. With most cases still being diagnosed at advanced stages, no improvement in survival prognosis is achieved with current diagnostic imaging approaches. In the absence of a dominant precancerous condition, several risk factors have been identified including family history, chronic pancreatitis, smoking, diabetes mellitus, as well as certain genetic disorders such as hereditary pancreatitis, cystic fibrosis, familial atypical multiple Most pancreatic carcinomas, however, remain sporadic. Current progress in experimental molecular techniques has enabled detailed understanding of the molecular processes of pancreatic cancer development. According to the latest information, malignant pancreatic transformation involves multiple oncogenes and tumor-suppressor genes that are involved in a variety of signaling pathways. The most characteristic aberrations (somatic point mutations and allelic losses) affect oncogenes and tumor-suppressor genes within RAS, AKT and Wnt signaling, and have a key role in transcription and proliferation, as well as systems that regulate the cell cycle (SMAD/DPC, CDKN2A/p16) and apoptosis (TP53). Understanding of the underlying molecular mechanisms should promote development of new methodology for early diagnosis and facilitate improvement in current approaches for pancreatic cancer treatment.

  7. Pancreatic panniculitis associated with acute pancreatitis and hemorrhagic pseudocysts: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Yong Suk; Kim, Mi Sung; Park, Chan Sub; Park, Ji Yeon; Park, Noh Hyuck [Kwandong Univ., Myongji Hospital, Goyang (Korea, Republic of)

    2012-10-15

    Pancreatic panniculitis is an inflammation and necrosis of fat at distant foci in patients with pancreatic disorders, most frequently, pancreatitis and pancreatic carcinoma. Clinically, pancreatic panniculitis is manifested by painless or painful subcutaneous nodules on the legs, buttocks, or trunk. The usual sites are the distal parts of the lower extremities. To the best of our knowledge, there have not been many reports for the radiologic findings of pancreatic panniculitis. In this article, we report a case of pancreatic panniculitis, including radiologic findings of CT and ultrasonography. The patient was presented with painful subcutaneous nodules on the trunk, and had underlying acute pancreatitis and hemorrhagic pseudocysts.

  8. Lazaroid U-74389G Administration in Pancreatic Ischemia-Reperfusion Injury: A Swine Model Encompassing Ischemic Preconditioning

    Directory of Open Access Journals (Sweden)

    Dimosthenis T Chrysikos

    2015-05-01

    Full Text Available Context The potential of lazaroid U-74389G in attenuating injury after ischemia and reperfusion has been reported in various organs. Objective The present study focuses specifically on the pancreas and aims to examine any effects of U-74389G in a swine model of pancreatic ischemia and reperfusion, encompassing ischemic preconditioning. Methods Twelve pigs, weighing 28–35 kg, were randomized into two experimental groups. Group A (control group, n=6: Two periods of ischemic preconditioning (5 min each separated by a 5- min rest interval; then ischemia time 30 min and reperfusion for 120 min. Group B (n=6: the same as above, with U-74389G intravenous injection in the inferior vena cava immediately prior to the initiation of reperfusion. Blood sampling and pancreatic biopsies were conducted at 0, 30, 60, 90 and 120 min after reperfusion. Results Repeated-measures ANOVA was undertaken to evaluate differences between the two study groups. No statistically significant differences were noted concerning the histopathological parameters in the control and therapygroups (P=0.563 for edema, P=0.241 for hemorrhage, P=0.256 for leukocyte infiltration, P=0.231 for acinar necrosis and P=0.438 for vacuolization. In accordance with the above, serum metabolic data (glucose, creatinine, urea, total and direct bilirubin, total calcium, amylase, lipase, SGOT/AST, SGPT/ALT, ALP, GGT, LDH, CRP, insulin were not significantly different between the two groups; similarly, tumor necrosis factor-α values (P=0.705 and tissue malondialdehyde levels (P=0.628 did not differ between the two groups. Conclusion This swine model of pancreatic ischemia and reperfusion, encompassing preconditioning, indicates that U-74389G lazaroid does not seem to exert protective effects from pancreatic damage.

  9. Severe Acute Pancreatitis in Pregnancy

    Directory of Open Access Journals (Sweden)

    Bahiyah Abdullah

    2015-01-01

    Full Text Available This is a case of a pregnant lady at 8 weeks of gestation, who presented with acute abdomen. She was initially diagnosed with ruptured ectopic pregnancy and ruptured corpus luteal cyst as the differential diagnosis. However she then, was finally diagnosed as acute hemorrhagic pancreatitis with spontaneous complete miscarriage. This is followed by review of literature on this topic. Acute pancreatitis in pregnancy is not uncommon. The emphasis on high index of suspicion of acute pancreatitis in women who presented with acute abdomen in pregnancy is highlighted. Early diagnosis and good supportive care by multidisciplinary team are crucial to ensure good maternal and fetal outcomes.

  10. Pharmacological approach to acute pancreatitis

    DEFF Research Database (Denmark)

    Bang, U.C.; Semb, S.; Nøjgaard, Camilla;

    2008-01-01

    The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may...... be useful as prophylaxis against post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The protease inhibitor gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL...

  11. How Grim is Pancreatic Cancer?

    Science.gov (United States)

    Weledji, Elroy Patrick; Enoworock, George; Mokake, Martin; Sinju, Motaze

    2016-04-15

    Pancreatic ductal carcinoma continues to be the most lethal malignancy with rising incidence. It is the fourth most common cause of cancer death in the western world due to its low treatment success rate. In addition, because of its rapid growth and silent course, diagnosis is often only established in the advanced stages. As one of the most aggressive malignancies, the treatment of this disease is a great challenge to clinicians. This paper reviewed the natural history of pancreatic cancer, the current clinical practice and the future in pancreatic cancer management. PMID:27471581

  12. Pancreatic Metastasis from Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Julian Jacob

    2010-01-01

    Full Text Available The pancreas is an unusual location for metastases from other primary cancers. Rarely, pancreatic metastases from kidney or colorectal cancers have been reported. However, a variety of other cancers may also spread to the pancreas. We report an exceptional case of pancreatic metastasis from prostate cancer. Differences in management between primary and secondary pancreatic tumors make recognition of metastases to the pancreas an objective of first importance. Knowledge of unusual locations for metastatic spread will reduce diagnostic delay and lead to a timely delivery of an appropriate treatment.

  13. Using pancreas tissue slices for in situ studies of islet of Langerhans and acinar cell biology.

    Science.gov (United States)

    Marciniak, Anja; Cohrs, Christian M; Tsata, Vasiliki; Chouinard, Julie A; Selck, Claudia; Stertmann, Julia; Reichelt, Saskia; Rose, Tobias; Ehehalt, Florian; Weitz, Jürgen; Solimena, Michele; Slak Rupnik, Marjan; Speier, Stephan

    2014-12-01

    Studies on the cellular function of the pancreas are typically performed in vitro on its isolated functional units, the endocrine islets of Langerhans and the exocrine acini. However, these approaches are hampered by preparation-induced changes of cell physiology and the lack of an intact surrounding. We present here a detailed protocol for the preparation of pancreas tissue slices. This procedure is less damaging to the tissue and faster than alternative approaches, and it enables the in situ study of pancreatic endocrine and exocrine cell physiology in a conserved environment. Pancreas tissue slices facilitate the investigation of cellular mechanisms underlying the function, pathology and interaction of the endocrine and exocrine components of the pancreas. We provide examples for several experimental applications of pancreas tissue slices to study various aspects of pancreas cell biology. Furthermore, we describe the preparation of human and porcine pancreas tissue slices for the validation and translation of research findings obtained in the mouse model. Preparation of pancreas tissue slices according to the protocol described here takes less than 45 min from tissue preparation to receipt of the first slices.

  14. Pancreatic tissue fluid pressure and pain in chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N

    1992-01-01

    A casual relation between pancreatic pressure and pain has been searched for decades but lack of appropriate methods for pressure measurements has hindered progress. During the 1980's the needle method has been used for direct intraoperative pancreatic tissue fluid pressure measurements and later...... for percutaneous sonographically-guided pressure measurements. Clinical and experimental evaluation of the method showed comparable results at intraoperative and percutaneous measurements and little week-to-week variation. Furthermore, comparable pressures in duct and adjacent pancreatic tissue were found, i.......e. the needle pressure mirrors the intraductal pressure. Comparisons of pain registrations, morphological and functional parameters with pancreatic tissue fluid pressure measurements have revealed a relation between pressure and pain which probably is causal. In patients with pain the high pressures previously...

  15. Role of Neurogenic Inflammation in Pancreatitis and Pancreatic Pain

    OpenAIRE

    Vera-Portocarrero, Louis; Karin N Westlund

    2005-01-01

    Pain arising from pancreatic diseases can become chronic and difficult to treat. There is a paucity of knowledge regarding the mechanisms that sensitize neural pathways that transmit noxious information from visceral organs. In this review, neurogenic inflammation is presented as a possible amplifier of the noxious signal from peripheral organs including the pancreas. The nerve pathways that transmit pancreatic pain are also reviewed as a conduit of the amplified signals. It is likely that co...

  16. Is acute recurrent pancreatitis a chronic disease?

    Institute of Scientific and Technical Information of China (English)

    Alberto Mariani; Pier Alberto Testoni

    2008-01-01

    Whether acute recurrent pancreaUtis is a chronic disease is still debated and a consensus is not still reached as demonstrated by differences in the classification of acute recurrent pancreatitis.There is major evidence for considering alcoholic pancreatitis as a chronic disease ab initio while chronic pancreatitis lesions detectable in biliary acute recurrent pancreatitis (ARP) seem a casual association.Cystic fibrosis transmembrane con ductance regulator (CFTR) gene mutation,hereditary and obstructive pancreatitis seem an acute disease that progress to chronic pancreatitis,likely as a consequence of the activation and proliferation of pancreatic stellate cells that produce and activate collagen and therefore fibrosis.From the diagnostic point of view,in patients with acute recurrent pancreatitis Endoscopic ultrasound (EUS) seems the more reliable technique for an accurate evaluation and follow-up of some ductal and parenchymal abnormalities suspected for early chronic pancreatitis.

  17. The role of diagnostic radiology in pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Elmas, Nevra E-mail: elmas@med.ege.edu.tr

    2001-05-01

    Acute pancreatitis is a frequent inflammatory and necrotic process of pancreas and peripancreatic field. To detect the presence of infected or sterile necrotic components and hemorrhage of the pancreatic paranchyma is important for therapeutic approach. Chronic pancreatitis is characterized by irreversible exocrine dysfunction, progressive loss of pancreatic tissue and morphological changes of the pancreatic canal. Imaging modalities play a primary role in the management of both acute and chronic pancreatitis. CT and MR imaging confirm the diagnosis and detect the severity of disease. In chronic pancreatitis, MRCP after Secretin administration, Spiral CT and endoscopic US seems to replace diagnostic ERCP. However differentiation of pseudotumor of chronic pancreatitis from the pancreatic carcinoma is difficult with either imaging modalities.

  18. Magnetic resonance imaging of pancreatitis: an update.

    Science.gov (United States)

    Manikkavasakar, Sriluxayini; AlObaidy, Mamdoh; Busireddy, Kiran K; Ramalho, Miguel; Nilmini, Viragi; Alagiyawanna, Madhavi; Semelka, Richard C

    2014-10-28

    Magnetic resonance (MR) imaging plays an important role in the diagnosis and staging of acute and chronic pancreatitis and may represent the best imaging technique in the setting of pancreatitis due to its unmatched soft tissue contrast resolution as well as non-ionizing nature and higher safety profile of intravascular contrast media, making it particularly valuable in radiosensitive populations such as pregnant patients, and patients with recurrent pancreatitis requiring multiple follow-up examinations. Additional advantages include the ability to detect early forms of chronic pancreatitis and to better differentiate adenocarcinoma from focal chronic pancreatitis. This review addresses new trends in clinical pancreatic MR imaging emphasizing its role in imaging all types of acute and chronic pancreatitis, pancreatitis complications and other important differential diagnoses that mimic pancreatitis. PMID:25356038

  19. Adenovirus-mediated hAQP1 expression in irradiated mouse salivary glands causes recovery of saliva secretion by enhancing acinar cell volume decrease.

    Science.gov (United States)

    Teos, L Y; Zheng, C-Y; Liu, X; Swaim, W D; Goldsmith, C M; Cotrim, A P; Baum, B J; Ambudkar, I S

    2016-07-01

    Head and neck irradiation (IR) during cancer treatment causes by-stander effects on the salivary glands leading to irreversible loss of saliva secretion. The mechanism underlying loss of fluid secretion is not understood and no adequate therapy is currently available. Delivery of an adenoviral vector encoding human aquaporin-1 (hAQP1) into the salivary glands of human subjects and animal models with radiation-induced salivary hypofunction leads to significant recovery of saliva secretion and symptomatic relief in subjects. To elucidate the mechanism underlying loss of salivary secretion and the basis for AdhAQP1-dependent recovery of salivary gland function we assessed submandibular gland function in control mice and mice 2 and 8 months after treatment with a single 15-Gy dose of IR (delivered to the salivary gland region). Salivary secretion and neurotransmitter-stimulated changes in acinar cell volume, an in vitro read-out for fluid secretion, were monitored. Consistent with the sustained 60% loss of fluid secretion following IR, a carbachol (CCh)-induced decrease in acinar cell volume from the glands of mice post IR was transient and attenuated as compared with that in cells from non-IR age-matched mice. The hAQP1 expression in non-IR mice induced no significant effect on salivary fluid secretion or CCh-stimulated cell volume changes, except in acinar cells from 8-month group where the initial rate of cell shrinkage was increased. Importantly, the expression of hAQP1 in the glands of mice post IR induced recovery of salivary fluid secretion and a volume decrease in acinar cells to levels similar to those in cells from non-IR mice. The initial rates of CCh-stimulated cell volume reduction in acinar cells from hAQP1-expressing glands post IR were similar to those from control cells. Altogether, the data suggest that expression of hAQP1 increases the water permeability of acinar cells, which underlies the recovery of fluid secretion in the salivary glands

  20. Adenovirus-mediated hAQP1 expression in irradiated mouse salivary glands causes recovery of saliva secretion by enhancing acinar cell volume decrease.

    Science.gov (United States)

    Teos, L Y; Zheng, C-Y; Liu, X; Swaim, W D; Goldsmith, C M; Cotrim, A P; Baum, B J; Ambudkar, I S

    2016-07-01

    Head and neck irradiation (IR) during cancer treatment causes by-stander effects on the salivary glands leading to irreversible loss of saliva secretion. The mechanism underlying loss of fluid secretion is not understood and no adequate therapy is currently available. Delivery of an adenoviral vector encoding human aquaporin-1 (hAQP1) into the salivary glands of human subjects and animal models with radiation-induced salivary hypofunction leads to significant recovery of saliva secretion and symptomatic relief in subjects. To elucidate the mechanism underlying loss of salivary secretion and the basis for AdhAQP1-dependent recovery of salivary gland function we assessed submandibular gland function in control mice and mice 2 and 8 months after treatment with a single 15-Gy dose of IR (delivered to the salivary gland region). Salivary secretion and neurotransmitter-stimulated changes in acinar cell volume, an in vitro read-out for fluid secretion, were monitored. Consistent with the sustained 60% loss of fluid secretion following IR, a carbachol (CCh)-induced decrease in acinar cell volume from the glands of mice post IR was transient and attenuated as compared with that in cells from non-IR age-matched mice. The hAQP1 expression in non-IR mice induced no significant effect on salivary fluid secretion or CCh-stimulated cell volume changes, except in acinar cells from 8-month group where the initial rate of cell shrinkage was increased. Importantly, the expression of hAQP1 in the glands of mice post IR induced recovery of salivary fluid secretion and a volume decrease in acinar cells to levels similar to those in cells from non-IR mice. The initial rates of CCh-stimulated cell volume reduction in acinar cells from hAQP1-expressing glands post IR were similar to those from control cells. Altogether, the data suggest that expression of hAQP1 increases the water permeability of acinar cells, which underlies the recovery of fluid secretion in the salivary glands