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Sample records for exocrine pancreas innocent

  1. Exocrine Pancreas in Cats With Diabetes Mellitus.

    PubMed

    Zini, E; Ferro, S; Lunardi, F; Zanetti, R; Heller, R S; Coppola, L M; Guscetti, F; Osto, M; Lutz, T A; Cavicchioli, L; Reusch, C E

    2016-01-01

    Pancreatitis has been described in cats with diabetes mellitus, although the number of studies currently available is very limited. In addition, ketoacidosis has been hypothesized to be associated with pancreatitis in diabetic cats. The aims of the present study were to investigate whether diabetic cats have pancreatitis and to determine if pancreatitis is more frequent with ketoacidosis. Samples of pancreas were collected postmortem from 37 diabetic cats, including 15 with ketoacidosis, and 20 control cats matched for age, sex, breed, and body weight. Sections were stained with hematoxylin and eosin, double-labeled for insulin/CD3, insulin/CD20, insulin/myeloperoxidase, insulin/PCNA, and glucagon/Ki67, and single-labeled for Iba1. A previously proposed semiquantitative score was used to characterize pancreatitis, along with counts of inflammatory cells. Scores of pancreatitis and the number of neutrophils, macrophages, and lymphocytes in the exocrine pancreas did not differ between diabetic and control cats or between diabetic cats with and without ketoacidosis. Of note, PCNA-positive acinar cells were increased (P = .002) in diabetic cats, particularly near islets (P < .001). Ki67-positive acinar cells were increased only near islets (P = .038). Ketoacidosis was not linked to proliferation. The results suggest that histopathologic evidence of pancreatitis may not be more frequent in diabetic cats and that ketoacidosis may not be associated with it at the time of death. Augmented PCNA-positive acinar cells might indicate increased proliferation due to chronic pancreatitis. The reason behind the prevalent proliferation of acinar cells surrounding pancreatic islets deserves further investigation. © The Author(s) 2015.

  2. Combined endocrine and exocrine tumours of the pancreas.

    PubMed

    Alzaraa, Ahmed; Udom, Valeri; Mousa, Husam; Alzein, Abdulhalem; Benhamida, Abduljalil; Dalal, Neha

    2007-09-14

    Cystic neoplasms of the pancreas comprise 10%-15% of pancreatic cystic lesions, with the serous cystadenoms being the commonest. The association of exocrine and endocrine tumours of the pancreas unrelated to Von Hipple Lindau disease is very rare. Very few cases have been reported in the literature. We present another case of both these tumours in one patient. A female patient was seen in the surgical clinic for a pain in the right groin. Clinical examination and investigations confirmed a diagnosis of combined endocrine and exocrine tumours of the pancreas. She underwent surgery and is under regular follow-up in the surgical clinic. Biphasic differentiation of pancreatic stem cell during embryological development could happen and may result in combined endocrine and exocrine tumours of the pancreas. Imaging studies are excellent in diagnosing theses lesions. Surgery has a central role and could be curative.

  3. Combined endocrine and exocrine tumours of the pancreas

    PubMed Central

    Alzaraa, Ahmed; Udom, Valeri; Mousa, Husam; Alzein, Abdulhalem; Benhamida, Abduljalil; Dalal, Neha

    2007-01-01

    Background Cystic neoplasms of the pancreas comprise 10%–15% of pancreatic cystic lesions, with the serous cystadenoms being the commonest. The association of exocrine and endocrine tumours of the pancreas unrelated to Von Hipple Lindau disease is very rare. Very few cases have been reported in the literature. We present another case of both these tumours in one patient. Case presentation A female patient was seen in the surgical clinic for a pain in the right groin. Clinical examination and investigations confirmed a diagnosis of combined endocrine and exocrine tumours of the pancreas. She underwent surgery and is under regular follow-up in the surgical clinic. Conclusion Biphasic differentiation of pancreatic stem cell during embryological development could happen and may result in combined endocrine and exocrine tumours of the pancreas. Imaging studies are excellent in diagnosing theses lesions. Surgery has a central role and could be curative. PMID:17868437

  4. Exocrine drainage in vascularized pancreas transplantation in the new millennium

    PubMed Central

    El-Hennawy, Hany; Stratta, Robert J; Smith, Fowler

    2016-01-01

    The history of vascularized pancreas transplantation largely parallels developments in immunosuppression and technical refinements in transplant surgery. From the late-1980s to 1995, most pancreas transplants were whole organ pancreatic grafts with insulin delivery to the iliac vein and diversion of the pancreatic ductal secretions to the urinary bladder (systemic-bladder technique). The advent of bladder drainage revolutionized the safety and improved the success of pancreas transplantation. However, starting in 1995, a seismic change occurred from bladder to bowel exocrine drainage coincident with improvements in immunosuppression, preservation techniques, diagnostic monitoring, general medical care, and the success and frequency of enteric conversion. In the new millennium, pancreas transplants are performed predominantly as pancreatico-duodenal grafts with enteric diversion of the pancreatic ductal secretions coupled with iliac vein provision of insulin (systemic-enteric technique) although the systemic-bladder technique endures as a preferred alternative in selected cases. In the early 1990s, a novel technique of venous drainage into the superior mesenteric vein combined with bowel exocrine diversion (portal-enteric technique) was designed and subsequently refined over the next ≥ 20 years to re-create the natural physiology of the pancreas with first-pass hepatic processing of insulin. Enteric drainage usually refers to jejunal or ileal diversion of the exocrine secretions either with a primary enteric anastomosis or with an additional Roux limb. The portal-enteric technique has spawned a number of newer and revisited techniques of enteric exocrine drainage including duodenal or gastric diversion. Reports in the literature suggest no differences in pancreas transplant outcomes irrespective of type of either venous or exocrine diversion. The purpose of this review is to examine the literature on exocrine drainage in the new millennium (the purported

  5. Pancreas-Specific Deletion of Prox1 Affects Development and Disrupts Homeostasis of the Exocrine Pancreas

    PubMed Central

    WESTMORELAND, JOBY J.; KILIC, GAMZE; SARTAIN, CAROLINE; SIRMA, SEMA; BLAIN, JENNIFER; REHG, JEROLD; HARVEY, NATASHA; SOSA–PINEDA, BEATRIZ

    2012-01-01

    BACKGROUND & AIMS The exocrine portion of the pancreas functions in digestion and preserves pancreatic homeostasis. Learning how this tissue forms during embryogenesis could improve our understanding of human pancreatic diseases. Expression of the homeo-box gene Prox1 in the exocrine pancreas changes throughout development in mice. We investigated the role of Prox1 in development of the exocrine pancreas in mice. METHODS Mice with pancreas-specific deletion of Prox1 (Prox1ΔPanc) were generated and their pancreatic tissues were analyzed using immunohistochemistry, transmission electron microscopy, histologic techniques, quantitative real-time polymerase chain reaction, immunoblotting, and morphometric analysis. RESULTS Loss of Prox1 from the pancreas led to multiple exocrine alterations, most notably premature acinar cell differentiation, increased ductal cell proliferation, altered duct morphogenesis, and imbalanced expression of claudin proteins. Prox1ΔPanc mice also had some minor alterations in islet cells, but beta-cell development was not affected. The exocrine congenital defects of Prox1ΔPanc pancreata appeared to initiate a gradual process of deterioration that resulted in extensive loss of acinar cells, lipomatosis, and damage to ductal tissue in adult mice. CONCLUSIONS Pancreas-specific deletion of Prox1 causes premature differentiation of acinar cells and poor elongation of epithelial branches; these defects indicate that Prox1 controls the expansion of tip progenitors in the early developing pancreas. During later stages of embryogenesis, Prox1 appears to regulate duct cell proliferation and morphogenesis. These findings identify Prox1 as an important regulator of pancreatic exocrine development. PMID:22178591

  6. The Cystic Fibrosis of Exocrine Pancreas

    PubMed Central

    Wilschanski, Michael

    2013-01-01

    The cystic fibrosis transmembrane conductance regulator (CFTR) protein is highly expressed in the pancreatic duct epithelia, and permits anions and water to enter the ductal lumen. This results in an increased volume of alkaline fluid allowing the highly concentrated proteins secreted by the acinar cells to remain in a soluble state. This work will expound on the pathophysiology and pathology caused by the malfunctioning CFTR protein with special reference to ion transport and acid-base abnormalities both in humans and animal models. We will also discuss the relationship between cystic fibrosis (CF) and pancreatitis, and outline present and potential therapeutic approaches in CF treatment relevant to the pancreas. PMID:23637307

  7. Purinergic receptors in the endocrine and exocrine pancreas

    PubMed Central

    2007-01-01

    The pancreas is a complex gland performing both endocrine and exocrine functions. In recent years there has been increasing evidence that both endocrine and exocrine cells possess purinergic receptors, which influence processes such as insulin secretion and epithelial ion transport. Most commonly, these processes have been viewed separately. In β cells, stimulation of P2Y1 receptors amplifies secretion of insulin in the presence of glucose. Nucleotides released from secretory granules could also contribute to autocrine/paracrine regulation in pancreatic islets. In addition to P2Y1 receptors, there is also evidence for other P2 and adenosine receptors in β cells (P2Y2, P2Y4, P2Y6, P2X subtypes and A1 receptors) and in glucagon-secreting α cells (P2X7, A2 receptors). In the exocrine pancreas, acini release ATP and ATP-hydrolysing and ATP-generating enzymes. P2 receptors are prominent in pancreatic ducts, and several studies indicate that P2Y2, P2Y4, P2Y11, P2X4 and P2X7 receptors could regulate secretion, primarily by affecting Cl− and K+ channels and intracellular Ca2+ signalling. In order to understand the physiology of the whole organ, it is necessary to consider the full complement of purinergic receptors on different cells as well as the structural and functional relation between various cells within the whole organ. In addition to the possible physiological function of purinergic receptors, this review analyses whether the receptors could be potential therapeutic targets for drug design aimed at treatment of pancreatic diseases. PMID:18368520

  8. Pancreas Volume and Fat Deposition in Diabetes and Normal Physiology: Consideration of the Interplay Between Endocrine and Exocrine Pancreas

    PubMed Central

    Saisho, Yoshifumi

    2016-01-01

    The pancreas is comprised of exocrine and endocrine components. Despite the fact that they are derived from a common origin in utero, these two compartments are often studied individually because of the different roles and functions of the exocrine and endocrine pancreas. Recent studies have shown that not only type 1 diabetes (T1D), but also type 2 diabetes (T2D), is characterized by a deficit in beta-cell mass, suggesting that pathological changes in the pancreas are critical events in the natural history of diabetes. In both patients with T1D and those with T2D, pancreas mass and exocrine function have been reported to be reduced. On the other hand, pancreas volume and pancreatic fat increase with obesity. Increased beta-cell mass with increasing obesity has also been observed in humans, and ectopic fat deposits in the pancreas have been reported to cause beta-cell dysfunction. Moreover, neogenesis and transdifferentiation from the exocrine to the endocrine compartment in the postnatal period are regarded as a source of newly formed beta-cells. These findings suggest that there is important interplay between the endocrine and exocrine pancreas throughout life. This review summarizes the current knowledge on physiological and pathological changes in the exocrine and endocrine pancreas (i.e., beta-cell mass), and discusses the potential mechanisms of the interplay between the two compartments in humans to understand the pathophysiology of diabetes better. PMID:28012279

  9. Effects of cholecystokinin receptor antagonist loxiglumide on rat exocrine pancreas.

    PubMed

    Nakano, S; Tachibana, I; Otsuki, M

    1994-07-01

    Effects of long-term administration of the cholecystokinin receptor antagonist loxiglumide on exocrine pancreas were studied in adult rats. Plasma concentrations of loxiglumide at 8 h after a single subcutaneous injection of 50 mg/kg body weight of loxiglumide were 3.2 +/- 0.8 microgram/ml, which were comparable to those at 12 h after oral administration of the same dose (3.7 +/- 0.9 microgram/ml). Eight hours' prior subcutaneous injection of loxiglumide (50 mg/kg body weight) significantly suppressed pancreatic exocrine secretion stimulated by an intravenous bolus injection of 50 ng/kg body weight caerulein compared with the control rats. Based on these results, in the first experiment, loxiglumide at a dose of 50 mg/kg body weight was given subcutaneously three times a day (low dose) for 6 days to adult rats fed a standard laboratory diet. Low dose of loxiglumide significantly decreased pancreatic wet weight (-14%) and pancreatic contents of protein (-26%), trypsin (-38%), and lipase (-68%), while having no significant effect on pancreatic contents of DNA and amylase. In the second experiment, three times higher dose of loxiglumide (150 mg/kg body weight) was given by an orogastric tube twice daily for 6 days. High dose of loxiglumide significantly decreased pancreatic weight (-11%) and contents of protein (-20%) and DNA (-22%), whereas it significantly increased amylase (+92%) and trypsin content (+20%).(ABSTRACT TRUNCATED AT 250 WORDS)

  10. ANF and exocrine pancreas: ultrastructural autoradiographic localization in acinar cells

    SciTech Connect

    Chabot, J.G.; Morel, G.; Belles-Isles, M.; Jeandel, L.; Heisler, S.

    1988-03-01

    Atrial natriuretic factor (ANF) binding sites have been recently demonstrated to be present in exocrine pancreas by an in vitro autoradiographic approach. An autoradiographic study was carried out to identify the exocrine cells containing ANF binding sites and to monitor the fate of /sup 125/I-labeled ANF in acinar cells after removal of pancreas at specific time intervals (1-30 min) after intravenous administration. At the light microscopic level, silver grains were found over acinar and centroacinar cells. Concomitant injection of an excess of unlabeled ANF inhibited the binding of labeled peptide by approximately 60%. At the electron microscopic level, the time-course study in acinar cells has revealed that of the cell compartments examined, plasma membrane, Golgi apparatus, mitochondria, and zymogen granules, the nucleus had distinct labeling patterns. Plasma membrane was maximally labeled 1 and 2 min after injection with /sup 125/I-ANF. Golgi apparatus was significantly labeled from 2 to 30 min after injection, mitochondria from 1 to 30 min after injection, zymogen granules at 1 and 15 min, and the nucleus only at 30 min. The lysosomal compartment was not labeled during the 30-min observation period. These results suggest that after binding to the plasma membrane, ANF is rapidly internalized and distributed to the intracellular organelles as a function of time. Labeling of the zymogen granules suggests that they may bind ANF and that the atrial peptide may be secreted by acinar cells. The significance of association of radioactivity with mitochondria and nuclei remains to be elucidated but may represent intracellular sites of action of ANF complementary to those on plasma membranes.

  11. AN EMBRYONIC CHICK PANCREAS ORGAN CULTURE MODEL: CHARACTERIZATION AND NEURAL CONTROL OF EXOCRINE RELEASE

    EPA Science Inventory

    An embryonic chick (Gallus domesticus) whole-organ pancreas culture system was developed for use as an in vitro model to study cholinergic regulation of exocrine pancreatic function. The culture system was examined for characteristic exocrine function and viability by measuring e...

  12. AN EMBRYONIC CHICK PANCREAS ORGAN CULTURE MODEL: CHARACTERIZATION AND NEURAL CONTROL OF EXOCRINE RELEASE

    EPA Science Inventory

    An embryonic chick (Gallus domesticus) whole-organ pancreas culture system was developed for use as an in vitro model to study cholinergic regulation of exocrine pancreatic function. The culture system was examined for characteristic exocrine function and viability by measuring e...

  13. Reprogramming of human exocrine pancreas cells to beta cells.

    PubMed

    Staels, Willem; Heremans, Yves; Heimberg, Harry

    2015-12-01

    One of the key promises of regenerative medicine is providing a cure for diabetes. Cell-based therapies are proving their safety and efficiency, but donor beta cell shortages and immunological issues remain major hurdles. Reprogramming of human pancreatic exocrine cells towards beta cells would offer a major advantage by providing an abundant and autologous source of beta cells. Over the past decade our understanding of transdifferentiation processes greatly increased allowing us to design reprogramming protocols that fairly aim for clinical trials.

  14. Analyses of pancreas development by generation of gfp transgenic zebrafish using an exocrine pancreas-specific elastaseA gene promoter

    SciTech Connect

    Wan Haiyan; Korzh, Svitlana; Li Zhen; Mudumana, Sudha Puttur; Korzh, Vladimir; Jiang Yunjin; Lin Shuo; Gong Zhiyuan . E-mail: dbsgzy@nus.edu.sg

    2006-05-15

    In contrast to what we know on development of endocrine pancreas, the formation of exocrine pancreas remains poorly understood. To create an animal model that allows observation of exocrine cell differentiation, proliferation, and morphogenesis in living animals, we used the zebrafish elastaseA (elaA) regulatory sequence to develop transgenic zebrafish that display highly specific exocrine pancreas expression of GFP in both larvae and adult. By following GFP expression, we found that the pancreas in early development was a relatively compact organ and later extended posterior along the intestine. By transferring the elaA:gfp transgene into slow muscle omitted mutant that is deficient in receiving Hedgehog signals, we further showed that Hedgehog signaling is required for exocrine morphogenesis but not for cell differentiation. We also applied the morpholino knockdown and toxin-mediated cell ablation approaches to this transgenic line. We showed that the development of exocrine pancreas is Islet-1 dependent. Injection of the diphtheria toxin A (DTA) construct under the elastaseA promoter resulted in selective ablation of exocrine cells while the endocrine cells and other endodermal derivatives (liver and intestine) were not affected. Thus, our works demonstrated the new transgenic line provided a useful experimental tool in analyzing exocrine pancreas development.

  15. Stimulus-secretion coupling in the developing exocrine pancreas

    SciTech Connect

    Chang, A.Y.S.

    1986-01-01

    Acinar cells of the embryonic pancreas are filled with zymogen granules containing, among others, the secretory protein, cholecystokinin (CCK) ..cap alpha..-amylase, the rate of amylase secretion from pancreatic lobules incubated in vitro was not increased in response to CCK. In contrast, the rate of CCK-stimulated amylase discharge from the neonatal pancreas was increased 4- to 8-fold above that seen in the embryonic gland. The postnatal amplification of secretory responsiveness was not associated with an increase in the level of /sup 125/I-CCK octapeptide specifically bound/cell equivalent or a change in the affinity of binding. Light microscopic autoradiography revealed a similar /sup 125/I-CCK-33 labeling pattern in pancreatic lobules from both ages with autoradiographic grains specifically localized at the periphery of acinar cells. In order to determine whether CCK binding is coupled to a rise in the cytosolic Ca/sup + +/concentration, (Ca/sup + +/)c, in the embryonic pancreas, /sup 45/Ca/sup + +/ efflux from tracer-loaded lobules was measured. Efflux of /sup 45/Ca/sup + +/ from both embryonic and neonatal pancreas was comparably increased in the presence of CCK.

  16. [Intraoperative cyto-histologic analysis in exocrine carcinoma of the pancreas; relation to choice of therapy].

    PubMed

    Arcuri, V; Ceppa, P; Colacino, R; Pastorino, S; Ravetti, G L; Tobia, F

    1984-12-01

    The Authors analyze the various cyto-histology techniques of investigation during surgical operation in the exocrine cancer of the pancreas, both on the results reported in literature and on their experiences based on a sample of 44 patients. They Authors, at the conclusion, single out the preferential technique in the citology by fine needle biopsy, for its reliability, practicality and lack of any complication.

  17. LRH-1 and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function.

    PubMed

    Holmstrom, Sam R; Deering, Tye; Swift, Galvin H; Poelwijk, Frank J; Mangelsdorf, David J; Kliewer, Steven A; MacDonald, Raymond J

    2011-08-15

    We have determined the cistrome and transcriptome for the nuclear receptor liver receptor homolog-1 (LRH-1) in exocrine pancreas. Chromatin immunoprecipitation (ChIP)-seq and RNA-seq analyses reveal that LRH-1 directly induces expression of genes encoding digestive enzymes and secretory and mitochondrial proteins. LRH-1 cooperates with the pancreas transcription factor 1-L complex (PTF1-L) in regulating exocrine pancreas-specific gene expression. Elimination of LRH-1 in adult mice reduced the concentration of several lipases and proteases in pancreatic fluid and impaired pancreatic fluid secretion in response to cholecystokinin. Thus, LRH-1 is a key regulator of the exocrine pancreas-specific transcriptional network required for the production and secretion of pancreatic fluid.

  18. Outcomes in Pancreas Transplantation With Exocrine Drainage Through a Duodenoduodenostomy Versus Duodenojejunostomy.

    PubMed

    Lindahl, J P; Horneland, R; Nordheim, E; Hartmann, A; Aandahl, E M; Grzyb, K; Haugaa, H; Kjøsen, G; Åsberg, A; Jenssen, T

    2017-07-11

    Until recently, pancreas transplantation has mostly been performed with exocrine drainage via duodenojejunostomy (DJ). Since 2012, DJ was substituted with duodenoduodenostomy (DD) in our hospital, allowing endoscopic access for biopsies. This study assessed safety profiles with DD versus DJ procedures and clinical outcomes with the DD technique in pancreas transplantation. DD patients (n = 117; 62 simultaneous pancreas-kidney [SPKDD ] and 55 pancreas transplantation alone [PTADD ] with median follow-up 2.2 years) were compared with DJ patients (n = 179; 167 SPKDJ and 12 PTADJ ) transplanted in the period 1998-2012 (pre-DD era). Postoperative bleeding and pancreas graft vein thrombosis requiring relaparotomy occurred in 17% and 9% of DD patients versus 10% (p = 0.077) and 6% (p = 0.21) in DJ patients, respectively. Pancreas graft rejection rates were still higher in PTADD patients versus SPKDD patients (p = 0.003). Hazard ratio (HR) for graft loss was 2.25 (95% CI 1.00, 5.05; p = 0.049) in PTADD versus SPKDD recipients. In conclusion, compared with the DJ procedure, the DD procedure did not reduce postoperative surgical complications requiring relaparatomy or improve clinical outcomes after pancreas transplantation despite serial pancreatic biopsies for rejection surveillance. It remains to be seen whether better rejection monitoring in DD patients translates into improved long-term pancreas graft survival. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  19. Exocrine pancreas trans-differentiation to hepatocytes--a physiological response to elevated glucocorticoid in vivo.

    PubMed

    Wallace, Karen; Marek, Carylyn J; Currie, Richard A; Wright, Matthew C

    2009-08-01

    Damage or ectopic expression of some growth factors can lead to the appearance of hepatocyte-like cells within the pancreas. Since glucocorticoids promote liver hepatocyte phenotype in vitro, the effect of glucocorticoid on pancreatic differentiation in vivo was examined. Treatment of rats with glucocorticoid for 25 days at levels that significantly inhibited weight gain resulted in the appearance of acinar cells expressing cytokeratin 7 and hepatocyte markers glutamine synthetase, carbamoyl phosphate synthetase and cytochrome P450 2E (the nomenclature employed is that given at http://drnelson.utmem.edu/CytochromeP450.html). Using a plastic pancreatic acinar cell line, this response was shown to be associated with changes in the regulation of WNT signalling-related gene expression and a repression of WNT signalling activity. These data suggest that a pathological response of the pancreas in vivo to elevated glucocorticoid is a differentiation of exocrine pancreatic cells or pancreatic progenitor cells to an hepatocyte-like phenotype.

  20. Proglucagon-Derived Peptides Do Not Significantly Affect Acute Exocrine Pancreas in Rats.

    PubMed

    Akalestou, Elina; Christakis, Ioannis; Solomou, Antonia M; Minnion, James S; Rutter, Guy A; Bloom, Stephen R

    2016-08-01

    Reports have suggested a link between treatment with glucagon-like peptide 1 (GLP-1) analogs and an increased risk of pancreatitis. Oxyntomodulin, a dual agonist of both GLP-1 and glucagon receptors, is currently being investigated as a potential antiobesity therapy, but little is known about its pancreatic safety. The aim of the study was to investigate the acute effect of oxyntomodulin and other proglucagon-derived peptides on the rat exocrine pancreas. Glucagon-like peptide 1, oxyntomodulin, glucagon, and exendin-4 were infused into anesthetized rats to measure plasma amylase concentration changes. In addition, the effect of each peptide on both amylase release and proliferation in rat pancreatic acinar (AR42J) and primary isolated ductal cells was determined. Plasma amylase did not increase postpeptide infusion, compared with vehicle and cholecystokinin; however, oxyntomodulin inhibited plasma amylase when coadministered with cholecystokinin. None of the peptides caused a significant increase in proliferation rate or amylase secretion from acinar and ductal cells. The investigated peptides do not have an acute effect on the exocrine pancreas with regard to proliferation and plasma amylase, when administered individually. Oxyntomodulin seems to be a potent inhibitor of amylase release, potentially making it a safer antiobesity agent regarding pancreatitis, compared with GLP-1 agonists.

  1. Effects of ghrelin on the structural complexity of exocrine pancreas tissue architecture.

    PubMed

    Pantic, Igor; Nesic, Dejan; Stevanovic, Darko; Starcevic, Vesna; Pantic, Senka; Trajkovic, Vladimir

    2013-06-01

    Recent studies have shown that ghrelin increases pancreatic exocrine secretion. However, the potential effects of ghrelin on the morphology of exocrine pancreas (EP) remain unknown. In this work, using fractal analysis, we demonstrate that centrally administered ghrelin increases structural complexity and tissue disorder in rat EP. The study was carried out on a total of 40 male Wistar rats divided into four groups (n = 10): ghrelin-treated animals (average age, 1.5 months), ghrelin-treated animals (8.5 months), and controls (1.5 and 8.5 months). The pancreas tissue sections were stained with hematoxylin/eosin and visualized by light microscopy. For each animal, the average values of tissue fractal dimension, lacunarity, as well as parameters of co-occurrence matrix texture, were determined using tissue digital micrographs. The results indicate that ghrelin administration increases EP fractal dimension and textural entropy, and decreases lacunarity, regardless of the age. To our knowledge, this is the first study to investigate the effects of ghrelin on the morphological properties of pancreatic tissue, and also the first to apply fractal and textural analysis methods in quantification of EP tissue architecture.

  2. Proglucagon-Derived Peptides Do Not Significantly Affect Acute Exocrine Pancreas in Rats

    PubMed Central

    Akalestou, Elina; Christakis, Ioannis; Solomou, Antonia M.; Minnion, James S.; Rutter, Guy A.; Bloom, Stephen R.

    2015-01-01

    Objectives Reports have suggested a link between treatment with glucagon-like peptide 1 (GLP-1) analogues and an increased risk of pancreatitis. Oxyntomodulin, a dual agonist of both GLP-1 and glucagon receptors, is currently being investigated as a potential anti-obesity therapy, but little is known about its pancreatic safety. The aim of this study was to investigate the acute effect of oxyntomodulin and other proglucagon-derived peptides on the rat exocrine pancreas. Methods GLP-1, oxyntomodulin, glucagon and exendin-4 were infused into anaesthetised rats to measure plasma amylase concentration changes. Additionally, the effect of each peptide on both amylase release and proliferation in rat pancreatic acinar (AR42J) and primary isolated ductal cells was determined. Results Plasma amylase did not increase post peptide infusion, compared to vehicle and cholecystokinin (CCK); however, oxyntomodulin inhibited plasma amylase when co-administered with CCK. None of the peptides caused a significant increase in proliferation rate or amylase secretion from acinar and ductal cells. Conclusions The investigated peptides do not have an acute effect on the exocrine pancreas with regard to proliferation and plasma amylase, when administered individually. Oxyntomodulin appears to be a potent inhibitor of amylase release, potentially making it a safer anti-obesity agent regarding pancreatitis, compared to GLP-1 agonists. PMID:26731187

  3. Neurogenin 3 Expressing Cells in the Human Exocrine Pancreas Have the Capacity for Endocrine Cell Fate

    PubMed Central

    Gomez, Danielle L.; O’Driscoll, Marci; Sheets, Timothy P.; Hruban, Ralph H.; Oberholzer, Jose; McGarrigle, James J.; Shamblott, Michael J.

    2015-01-01

    Neurogenin 3 (NGN3) is necessary and sufficient for endocrine differentiation during pancreatic development and is expressed by a population of progenitor cells that give rise exclusively to hormone-secreting cells within islets. NGN3 protein can be detected in the adult rodent pancreas only following certain types of injury, when it is transiently expressed by exocrine cells undergoing reprogramming to an endocrine cell fate. Here, NGN3 protein can be detected in 2% of acinar and duct cells in living biopsies of histologically normal adult human pancreata and 10% in cadaveric biopsies of organ donor pancreata. The percentage and total number of NGN3+ cells increase during culture without evidence of proliferation or selective cell death. Isolation of highly purified and viable NGN3+ cell populations can be achieved based on coexpression of the cell surface glycoprotein CD133. Transcriptome and targeted expression analyses of isolated CD133+ / NGN3+ cells indicate that they are distinct from surrounding exocrine tissue with respect to expression phenotype and Notch signaling activity, but retain high level mRNA expression of genes indicative of acinar and duct cell function. NGN3+ cells have an mRNA expression profile that resembles that of mouse early endocrine progenitor cells. During in vitro differentiation, NGN3+ cells express genes in a pattern characteristic of endocrine development and result in cells that resemble beta cells on the basis of coexpression of insulin C-peptide, chromogranin A and pancreatic and duodenal homeobox 1. NGN3 expression in the adult human exocrine pancreas marks a dedifferentiating cell population with the capacity to take on an endocrine cell fate. These cells represent a potential source for the treatment of diabetes either through ex vivo manipulation, or in vivo by targeting mechanisms controlling their population size and endocrine cell fate commitment. PMID:26288179

  4. The gastrin-releasing peptide analog bombesin preserves exocrine and endocrine pancreas morphology and function during parenteral nutrition.

    PubMed

    Pierre, Joseph F; Neuman, Joshua C; Brill, Allison L; Brar, Harpreet K; Thompson, Mary F; Cadena, Mark T; Connors, Kelsey M; Busch, Rebecca A; Heneghan, Aaron F; Cham, Candace M; Jones, Elaina K; Kibbe, Carly R; Davis, Dawn B; Groblewski, Guy E; Kudsk, Kenneth A; Kimple, Michelle E

    2015-09-15

    Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis.

  5. The gastrin-releasing peptide analog bombesin preserves exocrine and endocrine pancreas morphology and function during parenteral nutrition

    PubMed Central

    Pierre, Joseph F.; Neuman, Joshua C.; Brill, Allison L.; Brar, Harpreet K.; Thompson, Mary F.; Cadena, Mark T.; Connors, Kelsey M.; Busch, Rebecca A.; Heneghan, Aaron F.; Cham, Candace M.; Jones, Elaina K.; Kibbe, Carly R.; Davis, Dawn B.; Groblewski, Guy E.; Kudsk, Kenneth A.

    2015-01-01

    Stimulation of digestive organs by enteric peptides is lost during total parental nutrition (PN). Here we examine the role of the enteric peptide bombesin (BBS) in stimulation of the exocrine and endocrine pancreas during PN. BBS protects against exocrine pancreas atrophy and dysfunction caused by PN. BBS also augments circulating insulin levels, suggesting an endocrine pancreas phenotype. While no significant changes in gross endocrine pancreas morphology were observed, pancreatic islets isolated from BBS-treated PN mice showed a significantly enhanced insulin secretion response to the glucagon-like peptide-1 (GLP-1) agonist exendin-4, correlating with enhanced GLP-1 receptor expression. BBS itself had no effect on islet function, as reflected in low expression of BBS receptors in islet samples. Intestinal BBS receptor expression was enhanced in PN with BBS, and circulating active GLP-1 levels were significantly enhanced in BBS-treated PN mice. We hypothesized that BBS preserved islet function indirectly, through the enteroendocrine cell-pancreas axis. We confirmed the ability of BBS to directly stimulate intestinal enteroid cells to express the GLP-1 precursor preproglucagon. In conclusion, BBS preserves the exocrine and endocrine pancreas functions during PN; however, the endocrine stimulation is likely indirect, through the enteroendocrine cell-pancreas axis. PMID:26185331

  6. Generation of Functional Beta-Like Cells from Human Exocrine Pancreas

    PubMed Central

    Lima, Maria J.; Muir, Kenneth R.; Docherty, Hilary M.; McGowan, Neil W. A.; Forbes, Shareen; Heremans, Yves; Heimberg, Harry; Casey, John; Docherty, Kevin

    2016-01-01

    Transcription factor mediated lineage reprogramming of human pancreatic exocrine tissue could conceivably provide an unlimited supply of islets for transplantation in the treatment of diabetes. Exocrine tissue can be efficiently reprogrammed to islet-like cells using a cocktail of transcription factors: Pdx1, Ngn3, MafA and Pax4 in combination with growth factors. We show here that overexpression of exogenous Pax4 in combination with suppression of the endogenous transcription factor ARX considerably enhances the production of functional insulin-secreting β-like cells with concomitant suppression of α-cells. The efficiency was further increased by culture on laminin-coated plates in media containing low glucose concentrations. Immunocytochemistry revealed that reprogrammed cultures were composed of ~45% islet-like clusters comprising >80% monohormonal insulin+ cells. The resultant β-like cells expressed insulin protein levels at ~15–30% of that in adult human islets, efficiently processed proinsulin and packaged insulin into secretory granules, exhibited glucose responsive insulin secretion, and had an immediate and prolonged effect in normalising blood glucose levels upon transplantation into diabetic mice. We estimate that approximately 3 billion of these cells would have an immediate therapeutic effect following engraftment in type 1 diabetes patients and that one pancreas would provide sufficient tissue for numerous transplants. PMID:27243814

  7. Possible site of calcium regulation in rat exocrine pancreas cells: an X-ray microanalytical study

    SciTech Connect

    Roos, N.

    1988-03-01

    We analysed four subcellular compartments in rat exocrine pancreas cells, zymogen granules, cytoplasm surrounding the zymogen granules, mitochondria and cytoplasm in the basal part of the cells for sodium, magnesium, phosphorus, sulfur, chlorine, potassium and calcium content, using ultrathin frozen-dried cryosections. The highest concentrations of calcium were measured in the zymogen granules and the surrounding apical part of the cell containing Golgi apparatus, smooth endoplasmic reticulum and condensing vacuoles. Calcium concentrations in the basal part of the cells (mostly rough endoplasmic reticulum) were 60% lower than in the apical part of the cells. The lowest calcium concentrations were measured in mitochondria. The results suggest that other subcellular compartments than the rough endoplasmic reticulum and mitochondria might be involved in the intracellular Ca2+ regulation.

  8. Lnx2 ubiquitin ligase is essential for exocrine cell differentiation in the early zebrafish pancreas

    PubMed Central

    Won, Minho; Ro, Hyunju; Dawid, Igor B.

    2015-01-01

    The gene encoding the E3 ubiquitin ligase Ligand of Numb protein-X (Lnx)2a is expressed in the ventral-anterior pancreatic bud of zebrafish embryos in addition to its expression in the brain. Knockdown of Lnx2a by using an exon 2/intron 2 splice morpholino resulted in specific inhibition of the differentiation of ventral bud derived exocrine cell types, with little effect on endocrine cell types. A frame shifting null mutation in lnx2a did not mimic this phenotype, but a mutation that removed the exon 2 splice donor site did. We found that Lnx2b functions in a redundant manner with its paralog Lnx2a. Inhibition of lnx2a exon 2/3 splicing causes exon 2 skipping and leads to the production of an N-truncated protein that acts as an interfering molecule. Thus, the phenotype characterized by inhibition of exocrine cell differentiation requires inactivation of both Lnx2a and Lnx2b. Human LNX1 is known to destabilize Numb, and we show that inhibition of Numb expression rescues the Lnx2a/b-deficient phenotype. Further, Lnx2a/b inhibition leads to a reduction in the number of Notch active cells in the pancreas. We suggest that Lnx2a/b function to fine tune the regulation of Notch through Numb in the differentiation of cell types in the early zebrafish pancreas. Further, the complex relationships among genotype, phenotype, and morpholino effect in this case may be instructive in the ongoing consideration of morpholino use. PMID:26392552

  9. Lnx2 ubiquitin ligase is essential for exocrine cell differentiation in the early zebrafish pancreas.

    PubMed

    Won, Minho; Ro, Hyunju; Dawid, Igor B

    2015-10-06

    The gene encoding the E3 ubiquitin ligase Ligand of Numb protein-X (Lnx)2a is expressed in the ventral-anterior pancreatic bud of zebrafish embryos in addition to its expression in the brain. Knockdown of Lnx2a by using an exon 2/intron 2 splice morpholino resulted in specific inhibition of the differentiation of ventral bud derived exocrine cell types, with little effect on endocrine cell types. A frame shifting null mutation in lnx2a did not mimic this phenotype, but a mutation that removed the exon 2 splice donor site did. We found that Lnx2b functions in a redundant manner with its paralog Lnx2a. Inhibition of lnx2a exon 2/3 splicing causes exon 2 skipping and leads to the production of an N-truncated protein that acts as an interfering molecule. Thus, the phenotype characterized by inhibition of exocrine cell differentiation requires inactivation of both Lnx2a and Lnx2b. Human LNX1 is known to destabilize Numb, and we show that inhibition of Numb expression rescues the Lnx2a/b-deficient phenotype. Further, Lnx2a/b inhibition leads to a reduction in the number of Notch active cells in the pancreas. We suggest that Lnx2a/b function to fine tune the regulation of Notch through Numb in the differentiation of cell types in the early zebrafish pancreas. Further, the complex relationships among genotype, phenotype, and morpholino effect in this case may be instructive in the ongoing consideration of morpholino use.

  10. Exocrine pancreas ER stress is differentially induced by different fatty acids.

    PubMed

    Danino, Hila; Ben-Dror, Karin; Birk, Ruth

    2015-12-10

    Exocrine pancreas acinar cells have a highly developed endoplasmic reticulum (ER), accommodating their high protein production rate. Overload of dietary fat (typical to obesity) is a recognized risk factor in pancreatitis and pancreatic cancer. Dietary fat, especially saturated fat, has been suggested by others and us to induce an acinar lipotoxic effect. The effect of different dietary fatty acids on the ER stress response is unknown. We studied the effect of acute (24h) challenge with different fatty acids (saturated, mono and poly-unsaturated) at different concentrations (between 200 and 500µM, typical to normal and obese states, respectively), testing fat accumulation, ER stress indicators, X-box binding protein 1 (Xbp1) splicing and nuclear translocation, as well as unfolded protein response (UPR) transcripts and protein levels using exocrine pancreas acinar AR42J and primary cells. Acute exposure of AR42J cells to different fatty acids caused increased accumulation of triglycerides, dependent on the type of fat. Different FAs had different effects on ER stress: most notably, saturated palmitic acid significantly affected the UPR response, as demonstrated by altered Xbp1 splicing, elevation in transcript levels of UPR (Xbp, CHOP, Bip) and immune factors (Tnfα, Tgfβ), and enhanced Xbp1 protein levels and Xbp1 time-dependent nuclear translocation. Poly-unsaturated FAs caused milder elevation of ER stress markers, while mono-unsaturated oleic acid attenuated the ER stress response. Thus, various fatty acids differentially affect acinar cell fat accumulation and, apart from oleic acid, induce ER stress. The differential effect of the various fatty acids could have potential nutritional and therapeutic implications.

  11. Peptidergic and aminergic neurotransmitters of the exocrine pancreas of the Houbara bustard (Chlamydotis undulata).

    PubMed

    Mensah-Brown, E P; Pallot, D J

    2000-04-01

    The immunochemical distribution of peptidergic and aminergic neurotransmitters in the exocrine pancreas of the Houbara bustard, Chlamydotis undulata, was determined. Immunoreactivity to choline acetyltransferase (ChAT), vasoactive intestinal polypeptide (VIP), and galanin (Gal) occurred mainly as varicose terminals in the walls of capillaries around the acini and arterioles within the connective tissue. Neuronal cell bodies immunoreactive to ChAT were infrequently observed. Neuropeptide Y (NPY), pancreatic polypeptide (PP), and somatostatin (Som) were observed mainly in intra-acinar cell bodies but nerve fibers immunoreactive to these neuropeptides were also seen along the basal surfaces of the acini. Immunoreactivity to NPY and PP was also discernible in cells of the pancreatic ducts. In addition, NPY occurred as varicose terminals in vessels around the ducts. SP occurred rarely in interacinar ganglia. The distribution of tyrosine hydroxylase (TH) was similar to that of ChAT and, in addition, the occasional TH immunoreactive intra-acinar neuronal cell body was observed. Neuronal nitric oxide synthase (nNOS) occurred in neuronal cell bodies among the acinar cells as well as nerve fibers along the bases of the acini. The potential roles of these peptidergic and aminergic neurotransmitters in the neurohormonal control of pancreatic secretion are discussed.

  12. Concomitant radiochemotherapy in unresectable carcinoma of the exocrine pancreas: cost-effectiveness analysis.

    PubMed

    Cellini, N; Costamagna, G; Morganti, A G; Valentini, V; Macchia, G; Mutignani, M; Pandolfi, M; Trodella, L

    1999-01-01

    One of the principal therapeutic options in unresectable carcinoma of exocrine pancreas is concomitant radiochemotherapy. However, in current scientific literature cost analyses of this therapeutic modality are lacking. A payer-oriented cost-effectiveness analysis of concomitant radiochemotherapy was carried out. Outcomes and differences in costs relatively to two different therapeutic strategies were compared retrospectively: biliary drainage + observation (group 1); biliary drainage + concomitant radiochemotherapy (group 2). Cost-effectiveness was assessed based on the analysis of incremental cost of benefit in terms of survival in group 2. As incremental cost of group 2 was considered that of radiochemotherapy, costs of diagnosis and staging being similar in the two groups. The unit of measurement used was $/Lys (LYS = years of life saved). For estimates of cost-effectiveness in different clinical situations, a sensitivity analysis was carried out. The incremental cost of standard concomitant radiochemotherapy was shown to be $4,755. Incremental costs relatively to the situations of minimum and maximum treatment were shown to be $4,410 and $8,375, respectively. Median survival was 4.5 and 10 months in group 1 and 2 respectively (logrank: p = 0.0046). The benefit in terms of survival achieved by concomitant radiochemotherapy was shown to be 5.5 months equal to 0.46 years. Therefore, in the standard situation, the treatment cost-effectiveness can be estimated in: $4,755/0.46 years = $10,337/LYS, that is, the cost of a year of life saved was shown to be $10,337. Results of sensitivity analysis showed that cost-effectiveness can be estimated in the range $7,603 and $25,379/LYS. In conclusion, concomitant radiochemotherapy in patients with unresectable pancreatic carcinoma is able to improve the quality of life through the relief of related symptoms as well as median survival (10 vs 4.5 months). Costs of these benefits, even if considering better survival only, based

  13. Graded levels of Ptf1a differentially regulate endocrine and exocrine fates in the developing pancreas

    PubMed Central

    Dong, P. Duc Si; Provost, Elayne; Leach, Steven D.; Stainier, Didier Y.R.

    2008-01-01

    The mechanisms regulating pancreatic endocrine versus exocrine fate are not well defined. By analyzing the effects of Ptf1a partial loss of function, we uncovered novel roles for this transcription factor in determining pancreatic fates. In a newly identified hypomorphic ptf1a mutant, pancreatic cells that would normally express ptf1a and become exocrine cells, express the endocrine marker Isl1, indicating a cell fate switch. Surprisingly, a milder reduction of Ptf1a leads to an even greater increase of ectopic endocrine cells, suggesting that Ptf1a also plays a role in promoting endocrine development. We propose that low levels of Ptf1a promote endocrine fate, whereas high levels repress endocrine fate and promote exocrine fate. PMID:18519637

  14. Trend Toward Individualization of the Endocrine and Exocrine Portions of the Giant Anteater Pancreas (Myrmecophaga Tridactyla, Xenarthra).

    PubMed

    Iglesias, Luciana Pedrosa; Favaron, Phelipe Oliveira; Borghesi, Jéssica; Oliveira Carreira, Ana Claudia; Miglino, Maria Angelica; de Melo, Alan Perez Ferraz

    2016-10-27

    Considering the physiological importance of the pancreas as an endocrine and exocrine organ, this study described the characteristics of the gross and microscopic morphology of this organ using 16 Myrmecophaga tridactyla individuals. The pancreas was located in the left antimere of the body, was pale in colour and exhibited an elongated shape with a central body and lobulated surface. It was positioned in the abdomen, following the curvatura ventriculi major of the stomach, and was attached to the initial portion of the duodenum. The corpus pancreatis was elongated and showed a caudal curvature of 45°. The pancreas exhibited a facies dorsalis (related to the spleen and stomach) and a facies ventralis (related to the renal capsule and intestine). Macroscopically, a craniodorsal, medial, and caudoventral regions were identified, in addition to the left lobe. Structurally, the organ exhibited two distinct parts: the first had exocrine characteristics, consisting of acini and ducts; the second, which was the endocrine portion, consisted of the pancreatic islets, which were located in the medial, caudoventral and left lobe regions. Ultrastructural analysis identified secretory vesicles containing zymogen granules, mitochondria, Golgi apparatus and rough endoplasmic reticulum in pancreatic centroacinar cells. Morphological data on the anatomy of members of the Xenarthra have revealed important peculiarities of several organs and systems, adding great biological value to the representatives of this group. In addition, these studies significantly contribute not only to knowledge of the biology, taxonomy and, consequently, preservation of these animals but also to the discovery of new experimental models. Anat Rec, 2016. © 2016 Wiley Periodicals, Inc.

  15. Exocrine pancreatic insufficiency in adults: A shared position statement of the Italian association for the study of the pancreas

    PubMed Central

    Pezzilli, Raffaele; Andriulli, Angelo; Bassi, Claudio; Balzano, Gianpaolo; Cantore, Maurizio; Delle Fave, Gianfranco; Falconi, Massimo; Frulloni, Luca

    2013-01-01

    This is a medical position statement developed by the Exocrine Pancreatic Insufficiency collaborative group which is a part of the Italian Association for the Study of the Pancreas (AISP). We covered the main diseases associated with exocrine pancreatic insufficiency (EPI) which are of common interest to internists/gastroenterologists, oncologists and surgeons, fully aware that EPI may also occur together with many other diseases, but less frequently. A preliminary manuscript based on an extended literature search (Medline/PubMed, Cochrane Library and Google Scholar) of published reports was prepared, and key recommendations were proposed. The evidence was discussed at a dedicated meeting in Bologna during the National Meeting of the Association in October 2012. Each of the proposed recommendations and algorithms was discussed and an initial consensus was reached. The final draft of the manuscript was then sent to the AISP Council for approval and/or modification. All concerned parties approved the final version of the manuscript in June 2013. PMID:24307787

  16. Comparison of conventional surgical resection, radioactive implantation, and bypass procedures for exocrine carcinoma of the pancreas 1975-1980

    SciTech Connect

    Morrow, M.; Hilaris, B.; Brennan, M.F.

    1984-01-01

    To examine the efficacy of a variety of procedures for treatment of biopsy proven exocrine adenocarcinoma of the pancreas, a retrospective review of 231 patients surgically treated at a single institution from January 1975 through December 1980 was performed. Thirty-nine patients underwent resection for cure, of which 19 were conventional resection, 33 I125 implantation, 76 biliary or GI bypass, and 83 biopsy alone, a resectability rate of 16.9%. There was one pancreatic fistula in the implant group. Median survival following implant was 8 months (0%, 30-day mortality) and, for conventional resection (n . 19), 17 months with an inhospital mortality of 16%. Median survival excluding inhospital mortality was 17 months for the conventional resection group. For bypass, median survival was 4 months with an inhospital mortality of 14%. Of patients discharged from hospital, 5 of 16 (31%) survived 2 years in the conventional resection group, while 4 of 132 (3%) survived 2 years in the nonresected groups. Only one patient (5% of resected) has survived 4 years in the conventional resection group, although eight others are alive and at risk in this group. Resectability rate for patients referred with adenocarcinoma of the pancreas remains low. The only long-term survivors are in those patients undergoing resection. Local implantation with I125 requires prospective evaluation because of an apparent influence on palliation without significant morbidity.

  17. Autoantibodies against exocrine pancreas in Crohn's disease are directed against two antigens: the glycoproteins CUZD1 and GP2.

    PubMed

    Komorowski, Lars; Teegen, Bianca; Probst, Christian; Aulinger-Stöcker, Karola; Sina, Christian; Fellermann, Klaus; Stöcker, Winfried

    2013-11-01

    Autoantibodies against exocrine pancreas (PAb) have been reported to be pathognomonic markers of Crohn's disease (CD). Recently, the glycoprotein GP2 has been proposed as the exclusive target for PAb but two equally prevalent binding patterns can be observed in the indirect immunofluorescence test (IIFT) using cryosections of human pancreas: a reticulogranular and a droplet pattern. To identify autoantigens corresponding to the staining patterns. Different lectins were screened for their ability to immobilize PAb-reactive glycoproteins from cell free human pancreas. The glycoproteins were then purified via UEA-I affinity chromatography and identified by mass spectrometry. The two candidate autoantigens were separately expressed in HEK293 cells, and the recombinant cells applied as substrates in IIFT to analyze sera from 96 patients with CD, 89 controls and hybridoma supernatants during the generation of murine monoclonal antibodies. The UEA-I eluate was able to neutralize PAb reactivity of both patterns in IIFT. It contained two major constituents which were identified as the glycoproteins CUZD1 and GP2. With the recombinant cells, 35.4% of the CD patients exhibited positive reactions (CUZD1 alone 19.8%, GP2 alone 9.4%, and both antigens 6.2%). The reaction with the CUZD1 expressing cells was strictly correlated to the reticulogranular pattern, whereas the antibodies causing the droplet pattern stained the GP2 expressing cells. Antigen-capture ELISA using the newly generated monoclonal antibodies against CUZD1 and GP2 verified this relationship. The concordant reactivities of the different platforms can be regarded as a proof for the authenticity of the two identified autoantigens. Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.

  18. Effects of aflatoxins on performance and exocrine pancreas of broiler chickens.

    PubMed

    Marchioro, A; Mallmann, A O; Diel, A; Dilkin, P; Rauber, R H; Blazquez, F J H; Oliveira, M G A; Mallmann, C A

    2013-06-01

    The aim of this research was to evaluate, on a weekly basis, the effects of aflatoxins on the activity of digestive enzymes (alpha-amylase, lipase, and trypsin) in the pancreas as well as on the performance and histology of pancreas in broiler chickens over the course of 42 days. One thousand and eighty 1-day-old male Cobb broilers were divided into four treatments with 18 replicates and 15 birds per replicate (i.e., 270 broilers per treatment). Treatments were established according to the amount of aflatoxins added to the diet, as follows: T1 = 0 mg of aflatoxins per kilogram of feed (mg/kg); T2 = 0.7 mg/kg; T3 = 1.7 mg/kg; and T4 = 2.8 mg/kg. Pancreas sample collection was performed from one bird out of each replicate at 7, 14, 21, 28, 35, and 42 days of experiment, which yielded a total of 18 samples per treatment on each collection. Each sample was homogenized in distilled water, frozen in liquid nitrogen, lyophilized, and stored at -20 C until analysis. Performance parameters (body weight, feed consumption, and feed conversion rate) were measured at 21, 35, and 42 days of experiment. At the end of the experiment (42 days), six birds from each treatment were randomly chosen for histologic evaluation of the pancreas. The presence of aflatoxins in the diet induced a negative effect on all performance parameters. The pancreatic activity of lipase and alpha-amylase were significantly increased in treatments T3 and T4, while the specific activity of trypsin was only affected during treatment T4. In addition, several histologic changes were observed in the pancreas of birds receiving aflatoxin-contaminated feed. Aflatoxins present in the feed determined an increase in the activity of pancreatic enzymes in broilers, affecting the digestibility of the diet, thereby leading to losses in performance and productivity.

  19. In vivo spectroscopic photoacoustic tomography imaging of a far red fluorescent protein expressed in the exocrine pancreas of adult zebrafish

    NASA Astrophysics Data System (ADS)

    Liu, Mengyang; Schmitner, Nicole; Sandrian, Michelle G.; Zabihian, Behrooz; Hermann, Boris; Salvenmoser, Willi; Meyer, Dirk; Drexler, Wolfgang

    2014-03-01

    Fluorescent proteins brought a revolution in life sciences and biological research in that they make a powerful tool for researchers to study not only the structural and morphological information, but also dynamic and functional information in living cells and organisms. While green fluorescent proteins (GFP) have become a common labeling tool, red-shifted or even near infrared fluorescent proteins are becoming the research focus due to the fact that longer excitation wavelengths are more suitable for deep tissue imaging. In this study, E2-Crimson, a far red fluorescent protein whose excitation wavelength is 611 nm, was genetically expressed in the exocrine pancreas of adult zebrafish. Using spectroscopic all optical detection photoacoustic tomography, we mapped the distribution of E2-Crimson in 3D after imaging the transgenic zebrafish in vivo using two different wavelengths. With complementary morphological information provided by imaging the same fish using a spectral domain optical coherence tomography system, the E2-Crimson distribution acquired from spectroscopic photoacoustic tomography was confirmed in 2D by epifluorescence microscopy and in 3D by histology. To the authors' knowledge, this is the first time a far red fluorescent protein is imaged in vivo by spectroscopic photoacoustic tomography. Due to the regeneration feature of zebrafish pancreas, this work preludes the longitudinal studies of animal models of diseases such as pancreatitis by spectroscopic photoacoustic tomography. Since the effective penetration depth of photoacoustic tomography is beyond the transport mean free path length, other E2-Crimson labeled inner organs will also be able to be studied dynamically using spectroscopic photoacoustic tomography.

  20. Beta-COP localizes mainly to the cis-Golgi side in exocrine pancreas

    PubMed Central

    1993-01-01

    We examined the distribution of the non-clathrin-coated vesicle- associated coat protein beta-COP in rat exocrine pancreatic cells by immunogold cytochemistry. Labeling for beta-COP was found in the Golgi region (48%) where it was associated with vesicles and buds of approximately 50 nm, showing a characteristic approximately 10-nm-thick coat. The other half of the label was present in the cytoplasm, not associated with visible coats or membranes, with a minor fraction present on small clusters of tubules and vesicles. Clathrin-coated vesicles were typically located at the trans-side of the Golgi complex, and showed a thicker coat of approximately 18 nm. Of the total beta-COP labeling over the Golgi region, 68% occurred on the cis-side, 6% on the cisternae, 17% on the rims of the cisternae, and only 9% on the trans- side. For clathrin these figures were 16, 2, 4, and 78%, respectively. At the cis-Golgi side beta-COP was present in transitional areas (TA), on so-called peripheral elements (PE), consisting of tubules and vesicles located between the cup-shaped transitional elements (TE) of the RER and the cis-most Golgi cisternae. Label for Sec23p was also present in TA but was located closer to the TE, while beta-COP labeled PE were located near the cis-Golgi cisternae. Upon energy depletion, Golgi associated beta-COP was almost exclusively (86%) in spherical aggregates of 200-500 nm in diameter, whereas the cis-side (6%), the cisternae (1%), the rims (4%) and trans-side (3%) of the Golgi complex, were barely labeled; 50% of the total label remained in the cytoplasm. The aggregates were predominantly located at the cis-side of the Golgi stack, next to, but distinct from the Sec23p positive TA, that were devoid of beta-COP and had only a few recognizable vesicles left. Incubation with aluminum fluoride resulted in fragmentation of the Golgi complex into large clusters of beta-COP positive vesicles, while 50% of the label remained in the cytoplasm, as in control cells

  1. Immunohistochemical expression of growth factors in the exocrine pancreas of patients with chronic liver diseases.

    PubMed

    Mateescu, Garofiţa; Comănescu, Maria; Mehedinţi, Rodica; Niculescu, Zizi; Bold, Adriana; Panduru, Laurenţia; Cernea, Daniela

    2010-01-01

    Acute viral hepatitis has been reported to cause acute pancreatitis. It was also reported that exocrine pancreatic function is damaged in chronic liver disease (CLD). Growth factors stored in the extracellular matrix and released in the course of pancreatic degradation are major mediators of inductive processes. The immunostaining technique was used to evidence the changes of the expression of the growth factors in different pancreatic cells. VEGF and FGF-beta are involved in the angiogenesis processes and in the evolution of the pancreatic interstitial tissue in case of chronic pancreatitis. Theses markers can also be used for the diagnosis of pancreatitis, but their value is variable. They stimulate the pancreatic star cells, the myofibroblasts and play an important role in the genesis of the extracellular matrix and in the repairing of the tissue after the aggression. TGF beta is important for its role in cellular differentiation and growth and in the development of the fibrosis in liver and other organs. The present paper studies the immunohistochemical expression of these growth factors in pancreatic cells.

  2. Molecular consequences of cystic fibrosis transmembrane regulator (CFTR) gene mutations in the exocrine pancreas

    PubMed Central

    Ahmed, N; Corey, M; Forstner, G; Zielenski, J; Tsui, L-C; Ellis, L; Tullis, E; Durie, P

    2003-01-01

    Background and aims: We tested the hypothesis that the actual or predicted consequences of mutations in the cystic fibrosis transmembrane regulator gene correlate with the pancreatic phenotype and with measures of quantitative exocrine pancreatic function. Methods: We assessed 742 patients with cystic fibrosis for whom genotype and clinical data were available. At diagnosis, 610 were pancreatic insufficient, 110 were pancreatic sufficient, and 22 pancreatic sufficient patients progressed to pancreatic insufficiency after diagnosis. Results: We identified mutations on both alleles in 633 patients (85.3%), on one allele in 95 (12.8%), and on neither allele in 14 (1.9%). Seventy six different mutations were identified. The most common mutation was ΔF508 (71.3%) followed by G551D (2.9%), G542X (2.3%), 621+1G→T (1.2%), and W1282X (1.2%). Patients were categorized into five classes according to the predicted functional consequences of each mutation. Over 95% of patients with severe class I, II, and III mutations were pancreatic insufficient or progressed to pancreatic insufficiency. In contrast, patients with mild class IV and V mutations were consistently pancreatic sufficient. In all but four cases each genotype correlated exclusively with the pancreatic phenotype. Quantitative data of acinar and ductular secretion were available in 93 patients. Patients with mutations belonging to classes I, II, and III had greatly reduced acinar and ductular function compared with those with class IV or V mutations. Conclusion: The predicted or known functional consequences of specific mutant alleles correlate with the severity of pancreatic disease in cystic fibrosis. PMID:12865275

  3. Molecular consequences of cystic fibrosis transmembrane regulator (CFTR) gene mutations in the exocrine pancreas.

    PubMed

    Ahmed, N; Corey, M; Forstner, G; Zielenski, J; Tsui, L-C; Ellis, L; Tullis, E; Durie, P

    2003-08-01

    We tested the hypothesis that the actual or predicted consequences of mutations in the cystic fibrosis transmembrane regulator gene correlate with the pancreatic phenotype and with measures of quantitative exocrine pancreatic function. We assessed 742 patients with cystic fibrosis for whom genotype and clinical data were available. At diagnosis, 610 were pancreatic insufficient, 110 were pancreatic sufficient, and 22 pancreatic sufficient patients progressed to pancreatic insufficiency after diagnosis. We identified mutations on both alleles in 633 patients (85.3%), on one allele in 95 (12.8%), and on neither allele in 14 (1.9%). Seventy six different mutations were identified. The most common mutation was DeltaF508 (71.3%) followed by G551D (2.9%), G542X (2.3%), 621+1G-->T (1.2%), and W1282X (1.2%). Patients were categorized into five classes according to the predicted functional consequences of each mutation. Over 95% of patients with severe class I, II, and III mutations were pancreatic insufficient or progressed to pancreatic insufficiency. In contrast, patients with mild class IV and V mutations were consistently pancreatic sufficient. In all but four cases each genotype correlated exclusively with the pancreatic phenotype. Quantitative data of acinar and ductular secretion were available in 93 patients. Patients with mutations belonging to classes I, II, and III had greatly reduced acinar and ductular function compared with those with class IV or V mutations. The predicted or known functional consequences of specific mutant alleles correlate with the severity of pancreatic disease in cystic fibrosis.

  4. Investigation and characterization of the duct cell-enriching process during serum-free suspension and monolayer culture using the human exocrine pancreas fraction.

    PubMed

    Klein, Tino; Heremans, Yves; Heimberg, Harry; Pipeleers, Daniel; Madsen, Ole D; Serup, Palle; Heller, R Scott

    2009-01-01

    We aimed to characterize a serum-free culture system resulting in highly enriched duct cells from human exocrine pancreas. In addition, we tested the effect of vascular endothelial growth factor (VEGF) on endothelial cell proliferation and endocrine differentiation of the duct cells. The exocrine pellet fraction was cultivated in suspension followed by monolayer culture. Time course analysis of multiple acinar and duct cell markers was performed using reverse transcription-polymerase chain reaction and immunocytochemistry. The effects of VEGF and placental growth factor on the quantities of endothelial, duct, and endocrine cells and fibroblasts were investigated using computerized imaging analysis. Suspension culture of the exocrine material efficiently enriched the cultures for duct cells. Frequent acinar cell death as well as cell selective adherence of acinar cells to the culture dish was the underlying cause of the enrichment. Confocal microscopy demonstrated the virtual absence of cells coexpressing duct cell- and acinar cell-specific markers. The endothelial immunoreactivity of the suspension culture system could be increased 2-fold by VEGF treatment, yet no effect was observed on endocrine cell numbers. We have characterized a serum-free in vitro culture system to enrich human duct cells and further show that the contribution of acinoductal transdifferentiation to the enrichment of duct cells is negligible.

  5. Hormone-induced protein phosphorylation. I. Relationship between secretagogue action and endogenous protein phosphorylation in intact cells from the exocrine pancreas and parotid

    PubMed Central

    1982-01-01

    We undertook studies to determine whether secretagogue action on the exocrine pancreas and parotid is accompanied by phosphorylation of proteins in intact cells. For this purpose, rat pancreatic, and parotid lobules were preincubated with 32Pi for 45 min at 37 degrees C, washed, and then incubated at 37 degrees C in the presence or absence of secretagogues that effect discharge through different second messengers. Among a variety of polypeptides exhibiting enhanced phosphorylation in pancreatic lobules upon a 30-s incubation in the presence of the secretagogues carbamylcholine, cholecystokinin octapeptide, or secretin, one species with an Mr of 29,000 was especially notable for three reasons: (a) its enhanced level of phosphorylation was dependent on the dose of secretagogue used and was still apparent after incubation for 30 min at 37 degrees C; (b) an analogous phosphorylated polypeptide was observed in isoproterenol- stimulated parotid lobules; and (c) in both tissues its selective dephosphorylation was observed upon termination of stimulation by administration of atropine to carbamylcholine-stimulated pancreatic lobules and propranolol to isoproterenol-stimulated parotid lobules. These results suggest that the phosphorylation of one protein with an Mr of 29,000 is closely correlated both temporally and in a dose- dependent fashion with secretagogue action in both the exocrine pancreas and parotid. PMID:6296160

  6. Splenic vein thrombosis is associated with an increase in pancreas-specific complications and reduced survival in patients undergoing distal pancreatectomy for pancreatic exocrine cancer.

    PubMed

    Dedania, Nishi; Agrawal, Nidhi; Winter, Jordan M; Koniaris, Leonidas G; Rosato, Ernest L; Sauter, Patricia K; Leiby, Ben; Pequignot, Edward; Yeo, Charles J; Lavu, Harish

    2013-08-01

    Distal pancreatectomy and splenectomy (DPS) is the procedure of choice for the surgical treatment of pancreatic exocrine cancer localized to the body and tail of the pancreas. Splenic vein thrombosis (SVT) can occur in patients with malignant pancreatic exocrine tumors secondary to direct tumor invasion or compression of the splenic vein by mass effect. This study examines the effect of preoperative SVT on postoperative outcomes. In this retrospective cohort study, we queried our pancreatic surgery database to identify patients who underwent DPS from October 2005 to June 2011. These cases were evaluated for evidence of preoperative SVT on clinical records and cross-sectional imaging (CT,MRI, endoscopic US). Outcomes for patients with and without SVT were compared. From an overall cohort of 285 consecutive patients who underwent DPS during the study period, data were evaluated for 70 subjects who underwent surgery for pancreatic exocrine cancer (27 with SVT, 43 without SVT). The preoperative demographics and co-morbidities were similar between the groups, except the average age was higher for those without SVT (p<0.05). The median estimated blood loss was significantly higher in the SVT group (675 versus 250 ml, p=<0.001).While the overall morbidity rates were similar between the two groups (48 % SVT versus 56% no SVT, p=NS), the group with SVT had a significantly higher rate of pancreas-specific complications, including pancreatic fistula (33 versus 7 %,p<0.01) and delayed gastric emptying (15 versus 0%, p<0.02). Hospital readmission rates were similar between the groups(30 versus 28 %, p=NS). Patients without SVT had a trend toward longer median survival (40 versus 20.8 months),although the difference was not statistically significant (p=0.1). DPS for pancreatic ductal adenocarcinoma can be performed safely in patients with SVT, but with higher intraoperative blood loss, increased pancreas-specific complications, and a trend towards lower long-term survival rates

  7. CD1d Expression in Paneth Cells and Rat Exocrine Pancreas Revealed by Novel Monoclonal Antibodies Which Differentially Affect NKT Cell Activation

    PubMed Central

    Monzon-Casanova, Elisa; Steiniger, Birte; Schweigle, Stefanie; Clemen, Holger; Zdzieblo, Daniela; Starick, Lisa; Müller, Ingrid; Wang, Chyung-Ru; Rhost, Sara; Cardell, Susanna; Pyz, Elwira; Herrmann, Thomas

    2010-01-01

    Background CD1d is a nonpolymorphic MHC class I-like molecule which presents nonpeptide ligands, e.g. glycolipids, to NKT cells. These cells are known to have multiple effects on innate and adaptive immune responses and on the development of pathological conditions. In order to analyze CD1d expression and function in the rat, the first rat CD1d-specific monoclonal antibodies (mAbs) were generated. Methodology/Principal Findings Two mAbs, WTH-1 and WTH-2, were generated which bound equally well to cell surface-expressed rat and mouse CD1d. Their non-overlapping epitopes were mapped to the CD1d heavy chain. Flow cytometry and immunohistological analyses revealed a nearly identical degree and pattern of CD1d expression for hematopoieitic cells of both species. Notable is also the detection of CD1d protein in mouse and rat Paneth cells as well as the extremely high CD1d expression in acinar exocrine cells of the rat pancreas and the expression of CD4 on rat marginal zone B cells. Both mAbs blocked α-galactosylceramide recognition by primary rat and mouse NKT cells. Interestingly, the two mAbs differed in their impact on the activation of various autoreactive T cell hybridomas, including the XV19.2 hybridoma whose activation was enhanced by the WTH-1 mAb. Conclusions/Significance The two novel monoclonal antibodies described in this study, allowed the analysis of CD1d expression and CD1d-restricted T cell responses in the rat for the first time. Moreover, they provided new insights into mechanisms of CD1d-restricted antigen recognition. While CD1d expression by hematopoietic cells of mice and rats was extremely similar, CD1d protein was detected at not yet described sites of non-lymphatic tissues such as the rat exocrine pancreas and Paneth cells. The latter is of special relevance given the recently reported defects of Paneth cells in CD1d−/− mice, which resulted in an altered composition of the gut flora. PMID:20927351

  8. Multiple ribosomal proteins are expressed at high levels in developing zebrafish endoderm and are required for normal exocrine pancreas development.

    PubMed

    Provost, Elayne; Weier, Christopher A; Leach, Steven D

    2013-06-01

    Ribosomal protein L (rpl) genes are essential for assembly of the 60S subunit of the eukaryotic ribosome and may also carry out additional extra-ribosomal functions. We have identified a common expression pattern for rpl genes in developing zebrafish larvae. After initially widespread expression in early embryos, the expression of multiple rpl genes becomes increasingly restricted to the endoderm. With respect to the pancreas, rpl genes are highly expressed in ptf1a-expressing pancreatic progenitors at 48 hpf, suggesting possible functional roles in pancreatic morphogenesis and/or differentiation. Utilizing two available mutant lines, rpl23a(hi2582) and rpl6(hi3655b), we found that ptf1a-expressing pancreatic progenitors fail to properly expand in embryos homozygous for either of these genes. In addition to these durable homozygous phenotypes, we also demonstrated recoverable delays in ptf1a-expressing pancreatic progenitor expansion in rpl23a(hi2582) and rpl6(hi3655b) heterozygotes. Disruptions in ribosome assembly are generally understood to initiate a p53-dependent cellular stress response. However, concomitant p53 knockdown was unable to rescue normal pancreatic progenitor expansion in either rpl23a(hi2582) or rpl6(hi3655b) mutant embryos, suggesting required and p53-independent roles for rpl23a and rpl6 in pancreas development.

  9. Evidence that the (/sup 3/H)estradiol-binding protein in pancreas is localized in exocrine cells

    SciTech Connect

    Grossman, A.; Richardson, S.B.; Altszuler, N.; Lane, B.

    1985-06-01

    Extracts of rat pancreas contain significant amounts of an (/sup 3/H)estradiol-binding protein. The amount of steroid-binding activity that could be measured varied considerably depending on the tonicity of the homogenizing medium. High speed supernatants of homogenates initially prepared in isotonic buffer contained about 10% of the binding activity as homogenates prepared in hypotonic buffer. Extraction with hypotonic buffer of pellets obtained by the isotonic procedure yielded most of the remaining (/sup 3/H)estradiol-binding activity. In an attempt to avoid errors resulting from incomplete homogenization and to detect possible changes in intracellular distribution of (/sup 3/H)estradiol-binding activity, pancreata were initially homogenized in isotonic buffer and centrifuged at high speed (100,000 X g; 1 hr). The pellet was then extracted with hypotonic buffer and centrifuged again at high speed, and both supernatants were analyzed for (/sup 3/H)estradiol-binding and amylase activities. Two or 14 days after treatment of male rats with streptozotocin, no apparent decline or redistribution of (/sup 3/H)estradiol-binding activity to the cytosol was noted despite extensive alteration of beta-islet cells, as determined by electron microscopic examination of sections of these pancreata and significant loss of insulin, as measured by RIA. Amylase activity was unaffected 2 days after streptozotocin treatment, but was depressed to about 1% of control levels at 14 days. Administration of insulin to the latter group of animals resulted in return of amylase to normal levels and a modest increase (approximately 50%) in (/sup 3/H)estradiol-binding activity.

  10. Effect of atropine, ouabain, antimycin A, and A23187 on "trigger Ca2+ pool" in exocrine pancreas.

    PubMed

    Stolze, H; Schulz, I

    1980-04-01

    45Ca2+ fluxes have been analyzed in dispersed acinar cells prepared from rat pancreas. Sudden addition of carbamylcholine (CCh) to 45Ca2+-preloaded acinar cells at quasi-steady state for 45Ca2+ resulted in a quick 45Ca2+ release followed by a slower 45Ca2+ reuptake with net accumulation of 45Ca2+. Subsequent sudden addition of atropine caused a further transient increase in cellular 45Ca2+ followed by a slow decrease to a steady-state value. 45Ca2+ release could not be evoked a second time by pancreozymin when prestimulated with CCh. However, if CCh stimulation was abolished by an interposed step of atropine, restimulation by cholecystokinin-pancreozymin was possible. Addition of A23187 or antimycin A to cells induced a fast decrease in cellular 45Ca2+. This effect was not additive to the CCh effect. In ouabain-pretreated cells, the CCh-induced sudden loss of cellular 45Ca2+ was blocked by 60%. The following slow reuptake of 45Ca2+ was blocked completely. Subsequent addition of atropine caused a fast uptake of cellular 45Ca2+ with no secondary decline. The data are consistent with the following model: acetylcholine releases Ca2+ from a cellular "trigger pool" into the cytosol located in or near the cell membrane. Then Ca2+ is extruded from the cell via Ca2+ pumps partly by a Na+-dependent Ca2+ transport system (quick phase of 45Ca2+ release). Subsequently, due to increased Ca2+ permeability of the plasma membrane as induced by acetylcholine, Ca2+ influx occurs and Ca2+ is taken up from the cytosol into intracellular Ca2+ pools (slow 45Ca2+ reuptake phase). Atropine causes refilling of the trigger Ca2+ pool and return of the increased Ca2+ permeability of the plasma membrane back to the unstimulated state.

  11. Expression of a dominant-negative mutant TGF-beta type II receptor in transgenic mice reveals essential roles for TGF-beta in regulation of growth and differentiation in the exocrine pancreas.

    PubMed Central

    Böttinger, E P; Jakubczak, J L; Roberts, I S; Mumy, M; Hemmati, P; Bagnall, K; Merlino, G; Wakefield, L M

    1997-01-01

    Using a dominant-negative mutant receptor (DNR) approach in transgenic mice, we have functionally inactivated transforming growth factor-beta (TGF-beta) signaling in select epithelial cells. The dominant-negative mutant type II TGF-beta receptor blocked signaling by all three TGF-beta isoforms in primary hepatocyte and pancreatic acinar cell cultures generated from transgenic mice, as demonstrated by the loss of growth inhibitory and gene induction responses. However, it had no effect on signaling by activin, the closest TGF-beta family member. DNR transgenic mice showed increased proliferation of pancreatic acinar cells and severely perturbed acinar differentiation. These results indicate that TGF-beta negatively controls growth of acinar cells and is essential for the maintenance of a differentiated acinar phenotype in the exocrine pancreas in vivo. In contrast, such abnormalities were not observed in the liver. Additional abnormalities in the pancreas included fibrosis, neoangiogenesis and mild macrophage infiltration, and these were associated with a marked up-regulation of TGF-beta expression in transgenic acinar cells. This transgenic model of targeted functional inactivation of TGF-beta signaling provides insights into mechanisms whereby loss of TGF-beta responsiveness might promote the carcinogenic process, both through direct effects on cell proliferation, and indirectly through up-regulation of TGF-betas with associated paracrine effects on stromal compartments. PMID:9184209

  12. Lesions of the avian pancreas.

    PubMed

    Schmidt, Robert E; Reavill, Drury R

    2014-01-01

    Although not well described, occasional reports of avian exocrine and endocrine pancreatic disease are available. This article describes the lesions associated with common diseases of the avian pancreas reported in the literature and/or seen by the authors.

  13. Effect of L-aminocarnitine, an inhibitor of mitochondrial fatty acid oxidation, on the exocrine pancreas and liver in fasted rats.

    PubMed

    Nagy, I; Németh, J; Lászik, Z

    2000-01-01

    Fasting induces pancreatic secretory lipase, possibly through an increased utilization of fatty acids and/or ketone bodies by the acinar cells. To test this hypothesis, the effects of L-aminocarnitine (ACA), an inhibitor of mitochondrial beta-oxidation and ketone body formation, on the pancreatic enzyme composition were studied in rats. The characteristics and reversibility of the hepatic steatosis produced by ACA in fasted animals were also investigated. In fasted rats, ACA decreased the plasma levels of beta-hydroxybutyrate, glucose and insulin, but increased that of glucagon. Fasting for 3 days increased the pancreatic lipase content by 80%. Administration of ACA (3, 10 or 30 mg kg(-1) daily) for 3 days to fasted rats led to dose-related decreases in pancreatic lipase content, the fasting-induced increase was prevented even by the lowest dose. Nevertheless, ACA in the fasted rats likewise decreased the pancreatic contents of protein, amylase and trypsinogen to varying degrees, suggesting a general defect of protein synthesis. The 3-day treatment with ACA during fasting led to dose-related, marked increases in hepatic weight and triglyceride content. Light and electron microscopy revealed lipid vesicles of varying sizes in the hepatocytes; the fat deposition was predominant in the periportal zones of the hepatic lobules. By means of electron microscopy, lipid vacuoles were observed in the centroacinar cells, but not in the acinar cells of the pancreas. In rats treated with 30 mg kg(-1) of ACA daily for 3 days while they were fasted, cessation of ACA treatment and refeeding with normal chow led to normalization of the pancreatic enzyme contents within 6 days, and gradual and complete disappearance of the hepatic steatosis within 24 days. Microscopy also demonstrated complete recovery in both the liver and the pancreas. The results indicate that pancreatic secretory lipase induction during the adaptive phase of starvation is dependent on an unhindered mitochondrial

  14. Pancreatic Exocrine Insufficiency in Pancreatic Cancer.

    PubMed

    Vujasinovic, Miroslav; Valente, Roberto; Del Chiaro, Marco; Permert, Johan; Löhr, J-Matthias

    2017-02-23

    Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor's metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

  15. Deconstructing Pancreas Developmental Biology

    PubMed Central

    Benitez, Cecil M.; Goodyer, William R.

    2012-01-01

    The relentless nature and increasing prevalence of human pancreatic diseases, in particular, diabetes mellitus and adenocarcinoma, has motivated further understanding of pancreas organogenesis. The pancreas is a multifunctional organ whose epithelial cells govern a diversity of physiologically vital endocrine and exocrine functions. The mechanisms governing the birth, differentiation, morphogenesis, growth, maturation, and maintenance of the endocrine and exocrine components in the pancreas have been discovered recently with increasing tempo. This includes recent studies unveiling mechanisms permitting unexpected flexibility in the developmental potential of immature and mature pancreatic cell subsets, including the ability to interconvert fates. In this article, we describe how classical cell biology, genetic analysis, lineage tracing, and embryological investigations are being complemented by powerful modern methods including epigenetic analysis, time-lapse imaging, and flow cytometry-based cell purification to dissect fundamental processes of pancreas development. PMID:22587935

  16. Tumours of the pancreas.

    PubMed

    Kircher, C H; Nielsen, S W

    1976-01-01

    Tumours of the pancreas occur most commonly in dogs and cats and only rarely in other domestic species. The incidence of neoplasms, both exocrine and endocrine, increases with age. Exocrine adenocarcinomas are the most common malignant tumours and have three fairly distinct morphological patterns: small tubular, large tubular, and acinar cell (rare). They readily metastasize, usually before clinical signs are apparent. A "starry sky" pattern with clear histiocytes scattered among tumour cells is a regular feature of poorly differentiated areas of small tubular adenocarcinomas and undifferentiated carcinomas. Islet cell tumours occur in a significant number only in dogs. Metastases are found in about half of the tumours, but malignancy cannot always be predicted by the morphological appearance. Slightly more than half of the islet cell tumours reported in the dog have been associated with clinical signs of hypoglycaemia. Nodular hyperplasia and exocrine adenomas are sometimes difficult to differentiate. Adenomas are considered rare while nodular hyperplasia is common in old animals.

  17. [Specificities of the diagnostics and therapy of exocrine pancreatic insufficiency].

    PubMed

    Díté, P; Novotny, I; Kocna, P; Bojková, M; Kupka, T; Nechutová, H; Kianicka, B

    2013-01-01

    Exocrine pancreatic insufficiency develops steadily; however, the initial reduction in secretion is practically not diagnosable. More advanced stages, which usually replicate morphological changes, can be determined with tests which asses the exocrine pancreatic capacity. Substantial damage of the pancreas and replacement of viable parenchyma with connective tissue is accompanied by the occurrence of steatorrhoea. This corresponds to a reduction in exocrine pancreatic secretion below 10% of physiological secretion. Exocrine pancreatic secretion tests are still not sufficiently sensitive for diagnosing early stages of pancreas defects and thus are not suitable for diagnostics. Furthermore, detecting reduced exocrine secretion does not provide any information about the aetiology of the disease, e.g. inflammation/tumor. The most precise test is a costly examination, including a stimulation of the gland with enterohormones; however, breath tests are usually recommended for the assessment of exocrine insufficiency therapy. Exocrine pancreatic insufficiency therapy consists of administering drugs containing pancreatin (amylase, lipase, and peptidase) to patients diagnosed with steatorrhoea, manifest pancreatic insufficiency. As standard, capsules containing microparticles of 1-2mm are recommended. They have a protective coating that prevents inactivation in the microparticles of the contained enzymes by gastric hydrochloric acid. The drug should be administered during each meal, i.e. several times a day. The most common mistake during pancreatic enzyme therapy is under dosage. The following rule applies to patients with digestive insufficiency: 40,000-50,000 UNT of lipase are to be administered during "main meals" and 25,000 UNT of lipase during morning or afternoon snacks. The drug should be taken during the meal; insufficient treatment and dosage are associated with insufficient digestion and absorption ofa number of substances and also with pancreatic malabsorption.

  18. Innocent Until Proven Guilty

    ERIC Educational Resources Information Center

    Case, Catherine; Whitaker, Douglas

    2016-01-01

    In the criminal justice system, defendants accused of a crime are presumed innocent until proven guilty. Statistical inference in any context is built on an analogous principle: The null hypothesis--often a hypothesis of "no difference" or "no effect"--is presumed true unless there is sufficient evidence against it. In this…

  19. Why Confessions Trump Innocence

    ERIC Educational Resources Information Center

    Kassin, Saul M.

    2012-01-01

    As illustrated by the story of Amanda Knox and many others wrongfully convicted, false confessions often trump factual innocence. Focusing on consequences, recent research suggests that confessions are powerfully persuasive as a matter of logic and common sense; that many false confessions contain richly detailed narratives and accurate crime…

  20. Why Confessions Trump Innocence

    ERIC Educational Resources Information Center

    Kassin, Saul M.

    2012-01-01

    As illustrated by the story of Amanda Knox and many others wrongfully convicted, false confessions often trump factual innocence. Focusing on consequences, recent research suggests that confessions are powerfully persuasive as a matter of logic and common sense; that many false confessions contain richly detailed narratives and accurate crime…

  1. Innocent Until Proven Guilty

    ERIC Educational Resources Information Center

    Case, Catherine; Whitaker, Douglas

    2016-01-01

    In the criminal justice system, defendants accused of a crime are presumed innocent until proven guilty. Statistical inference in any context is built on an analogous principle: The null hypothesis--often a hypothesis of "no difference" or "no effect"--is presumed true unless there is sufficient evidence against it. In this…

  2. Pancreatic Exocrine Insufficiency in Pancreatic Cancer

    PubMed Central

    Vujasinovic, Miroslav; Valente, Roberto; Del Chiaro, Marco; Permert, Johan; Löhr, J.-Matthias

    2017-01-01

    Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor’s metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes. PMID:28241470

  3. Pancreatic exocrine function testing

    SciTech Connect

    Goff, J.S.

    1981-11-01

    It is important to understand which pancreatic function tests are available and how to interpret them when evaluating patients with malabsorption. Available direct tests are the secretin stimulation test, the Lundh test meal, and measurement of serum or fecal enzymes. Indirect tests assess pancreatic exocrine function by measuring the effect of pancreatic secretion on various nutrients. These include triglycerides labeled with carbon 14, cobalamin labeled with cobalt 57 and cobalt 58, and para-aminobenzoic acid bound to a dipeptide. Of all these tests the secretin stimulation test is the most accurate and reliable if done by experienced personnel. However, the indirect tests are simpler to do and appear to be comparable to the secretin test at detecting pancreatic exocrine insufficiency. These indirect tests are becoming clinically available and clinicians should familiarize themselves with the strengths and weaknesses of each.

  4. Anglicising psychoanalysis innocently.

    PubMed

    Bourne, Harold

    2010-06-01

    Finding Freud not properly on his feet, Rycroft turned him upright. Not by producing yet another school of psychoanalysis, but by pseudo-innocently amending its German polysyllabic script radically into English, and so revealing too how humanity is distinctly and to the very depths a symbolising animal. The present study describes how he contrived both to achieve all this, along with eminence in English society, and perversely to remain unconsciously and steadfastly little known or audible in the world of psychoanalysis.

  5. Exocrine pancreatic insufficiency in the cat.

    PubMed

    Steiner, Jörg M

    2012-08-01

    Exocrine pancreatic insufficiency (EPI) is a syndrome caused by an insufficient amount of pancreatic digestive enzymes in the small intestine. Clinical signs most commonly reported in cats with EPI are weight loss, loose and voluminous stools, steatorrhea, polyphagia, and in some cases a greasy soiling of the hair coat in the perianal region. Serum feline trypsin-like immunoreactivity concentration is the diagnostic test of choice for the diagnosis of affected cats. Treatment of cats with EPI consists of enzyme supplementation with either a powdered pancreatic extract or raw pancreas. Most cats with EPI also have severely decreased serum cobalamin concentrations and may require lifelong parenteral cobalamin supplementation. Most cats respond well to therapy and can have a normal life expectancy and quality of life.

  6. Impaired growth of pancreatic exocrine cells in transgenic mice expressing human activin {beta}E subunit

    SciTech Connect

    Hashimoto, Osamu . E-mail: ohashim@vmas.kitasato-u.ac.jp; Ushiro, Yuuki; Sekiyama, Kazunari; Yamaguchi, Osamu; Yoshioka, Kazuki; Mutoh, Ken-Ichiro; Hasegawa, Yoshihisa

    2006-03-10

    Activins, TGF-{beta} superfamily members, have multiple functions in a variety of cells and tissues. Recently, additional activin {beta} subunit genes, {beta}C and {beta}E, have been identified. To explore the role of activin E, we created transgenic mice overexpressing human activin {beta}E 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.

  7. Inhibitory effects of acetylsalicylic acid on exocrine pancreatic carcinogenesis.

    PubMed

    Yıldız, H; Oztas, H; Yıldız, D; Koc, A; Kalipci, E

    2013-05-01

    We investigated short (6 months) and long (12 months) term inhibitory effects of low (200 ppm) and high (400 ppm) dosages of acetylsalicylic acid (aspirin) on exocrine pancreatic carcinogenesis. It is known that exocrine pancreatic carcinogenesis can be detected by the presence of atypical acinar cell foci (AACF) in pancreas. We investigated possible inhibitory effects of acetylsalicylic acid in an azaserine-treated rat model. AACF were produced in rats by injection with azaserine according to previous studies. Our findings showed that the number, volume and diameter of pancreatic AACF were reduced after acetylsalicylic acid application. These observations suggest that acetylsalicylic acid may exert a protective effect against neoplastic development of pancreatic acinar cells in azaserine injected rats. Our findings corroborate reports in the literature concerning the effects of aspirin in reducing neoplastic development.

  8. Pancreas Transplantation

    MedlinePlus

    The pancreas is a gland behind your stomach and in front of your spine. It produces the juices that ... hormones that help control blood sugar levels. A pancreas transplant is surgery to place a healthy pancreas ...

  9. Mutations in the CEL VNTR cause a syndrome of diabetes and pancreatic exocrine dysfunction.

    PubMed

    Raeder, Helge; Johansson, Stefan; Holm, Pål I; Haldorsen, Ingfrid S; Mas, Eric; Sbarra, Véronique; Nermoen, Ingrid; Eide, Stig A; Grevle, Louise; Bjørkhaug, Lise; Sagen, Jørn V; Aksnes, Lage; Søvik, Oddmund; Lombardo, Dominique; Molven, Anders; Njølstad, Pål Rasmus

    2006-01-01

    Dysfunction of the exocrine pancreas is observed in diabetes, but links between concurrent exocrine and endocrine pancreatic disease and contributing genetic factors are poorly characterized. We studied two families with diabetes and exocrine pancreatic dysfunction by genetic, physiological and in vitro functional studies. A genome-wide screen in Family 1 linked diabetes to chromosome 9q34 (maximal lod score 5.07). Using fecal elastase deficiency as a marker of exocrine pancreatic dysfunction refined the critical chromosomal region to 1.16 Mb (maximal lod score 11.6). Here, we identified a single-base deletion in the variable number of tandem repeats (VNTR)-containing exon 11 of the carboxyl ester lipase (CEL) gene, a major component of pancreatic juice and responsible for the duodenal hydrolysis of cholesterol esters. Screening subjects with maturity-onset diabetes of the young identified Family 2, with another single-base deletion in CEL and a similar phenotype with beta-cell failure and pancreatic exocrine disease. The in vitro catalytic activities of wild-type and mutant CEL protein were comparable. The mutant enzyme was, however, less stable and secreted at a lower rate. Furthermore, we found some evidence for an association between common insertions in the CEL VNTR and exocrine dysfunction in a group of 182 unrelated subjects with diabetes (odds ratio 4.2 (1.6, 11.5)). Our findings link diabetes to the disrupted function of a lipase in the pancreatic acinar cells.

  10. Augmented damage of islets by impaired exocrine acinar cells undergoing apoptosis that is possibly converted to necrosis during isolation.

    PubMed

    Elgendy, Hamed; Okitsu, Teru; Kimura, Yasuko; Liu, Xibao; Nafady-Hego, Hanaa; Kurata, Jiro; Teramae, Hiroki; Elbahrawy, Ashraf; Uemoto, Shinji; Fukuda, Kazuhiko

    2011-01-01

    Islet damage attributed to impaired exocrine cells during pancreas preservation and isolation procedure remains elusive, although released exocrine enzymes could directly damage islets. The aim of this study is to investigate the cellular mechanisms associated with exocrine cells and their possible impact on the islet cell survival and function after isolation. Mouse pancreata were stored in cold University of Wisconsin preservation solution for 0, 24 and 48 h and incubated with or without collagenase at 37°C for 15 min. During preservation, the percentage of exocrine cells with necrosis, which means impaired cellular membrane that allows intracellular enzymes to be released, remains low (< 10%) regardless of preservation time; whereas the percentage of exocrine cells with apoptosis, which means impaired nucleus and possible intact cellular membrane, increases over time of preservation. After collagenase-free incubation, however, the percentage of exocrine cells with necrosis became higher in longer preservation time, and more than 60% of the necrotic exocrine cells contained apoptosis as well. Islet cells located in pancreata with intact structure are almost kept away either from necrotic or apoptotic changes even after 48 h preservation followed by collagenase-free incubation. However, when islets are isolated after collagenase-containing incubation, the percentage of islet cells with necrosis increases over time of preservation up to approximately 40%. This study suggests that exocrine cells with necrosis could cause damage of isolated islets when the pancreas is dissociated and that the necrosis in exocrine cells might be induced mainly as the conversion from apoptosis that has already existed during preservation.

  11. Purinergic signalling in the pancreas in health and disease.

    PubMed

    Burnstock, G; Novak, I

    2012-05-01

    Pancreatic cells contain specialised stores for ATP. Purinergic receptors (P2 and P1) and ecto-nucleotidases are expressed in both endocrine and exocrine calls, as well as in stromal cells. The pancreas, especially the endocrine cells, were an early target for the actions of ATP. After the historical perspective of purinergic signalling in the pancreas, the focus of this review will be the physiological functions of purinergic signalling in the regulation of both endocrine and exocrine pancreas. Next, we will consider possible interaction between purinergic signalling and other regulatory systems and their relation to nutrient homeostasis and cell survival. The pancreas is an organ exhibiting several serious diseases - cystic fibrosis, pancreatitis, pancreatic cancer and diabetes - and some are associated with changes in life-style and are increasing in incidence. There is upcoming evidence for the role of purinergic signalling in the pathophysiology of the pancreas, and the new challenge is to understand how it is integrated with other pathological processes.

  12. Exocrine pancreatic disorders in transsgenic mice expressing human keratin 8

    PubMed Central

    Casanova, M. Llanos; Bravo, Ana; Ramírez, Angel; Escobar, Gabriela Morreale de; Were, Felipe; Merlino, Glenn; Vidal, Miguel; Jorcano, José L.

    1999-01-01

    Keratins K8 and K18 are the major components of the intermediate-filament cytoskeleton of simple epithelia. Increased levels of these keratins have been correlated with various tumor cell characteristics, including progression to malignancy, invasive behavior, and drug sensitivity, although a role for K8/K18 in tumorigenesis has not yet been demonstrated. To examine the function of these keratins, we generated mice expressing the human K8 (hk8) gene, which leads to a moderate keratin-content increase in their simple epithelia. These mice displayed progressive exocrine pancreas alterations, including dysplasia and loss of acinar architecture, redifferentiation of acinar to ductal cells, inflammation, fibrosis, and substitution of exocrine by adipose tissue, as well as increased cell proliferation and apoptosis. Histological changes were not observed in other simple epithelia, such as the liver. Electron microscopy showed that transgenic acinar cells have keratins organized in abundant filament bundles dispersed throughout the cytoplasm, in contrast to control acinar cells, which have scarce and apically concentrated filaments. The phenotype found was very similar to that reported for transgenic mice expressing a dominant-negative mutant TGF-β type II receptor (TGFβRII mice). We show that these TGFβRII mutant mice also have elevated K8/K18 levels. These results indicate that simple epithelial keratins play a relevant role in the regulation of exocrine pancreas homeostasis and support the idea that disruption of mechanisms that normally regulate keratin expression in vivo could be related to inflammatory and neoplastic pancreatic disorders. PMID:10359568

  13. Cellular and molecular mechanisms coordinating pancreas development.

    PubMed

    Bastidas-Ponce, Aimée; Scheibner, Katharina; Lickert, Heiko; Bakhti, Mostafa

    2017-08-15

    The pancreas is an endoderm-derived glandular organ that participates in the regulation of systemic glucose metabolism and food digestion through the function of its endocrine and exocrine compartments, respectively. While intensive research has explored the signaling pathways and transcriptional programs that govern pancreas development, much remains to be discovered regarding the cellular processes that orchestrate pancreas morphogenesis. Here, we discuss the developmental mechanisms and principles that are known to underlie pancreas development, from induction and lineage formation to morphogenesis and organogenesis. Elucidating such principles will help to identify novel candidate disease genes and unravel the pathogenesis of pancreas-related diseases, such as diabetes, pancreatitis and cancer. © 2017. Published by The Company of Biologists Ltd.

  14. Under Utilization of Pancreas Transplants in Cystic Fibrosis Recipients in the United Network Organ Sharing (UNOS) Data 1987-2014.

    PubMed

    Usatin, D J; Perito, E R; Posselt, A M; Rosenthal, P

    2016-05-01

    Despite a high prevalence of pancreatic endocrine and exocrine insufficiency in cystic fibrosis (CF), pancreas transplantation is rarely reported. United Network for Organ Sharing (UNOS) data were used to examine utilization of pancreas transplant and posttransplant outcomes in CF patients. Between 1987-2014, CF patients (N = 4600) underwent 17 liver-pancreas, three lung-pancreas, one liver-lung pancreas, four kidney-pancreas, and three pancreas-only transplants. Of the 303 CF patients who received liver transplantation, 20% had CF-related diabetes (CFRD) before transplantation, and nine of those received a liver-pancreas transplant. Of 4241 CF patients who underwent lung transplantation, 33% had CFRD before transplantation, and three of those received a pancreas transplant. Of 49 CF patients who received a liver-lung transplant, 57% had CFRD before transplantation and one received a pancreas transplant. Posttransplantation diabetes developed in 7% of CF pancreas transplant recipients versus 24% of CF liver and 29% of CF lung recipients. UNOS has no data on pancreas exocrine insufficiency. Two-year posttransplantation survival was 88% after liver-pancreas transplant, 33% after lung-pancreas transplant, and 100% after pancreas-kidney and pancreas-only transplants. Diabetes is common pretransplantation and posttransplantation in CF solid organ transplant recipients, but pancreas transplantation remains rare. Further consideration of pancreas transplant in CF patients undergoing other solid organ transplant may be warranted. © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

  15. Actual innocence: is death different?

    PubMed

    Acker, James R

    2009-01-01

    Supreme Court jurisprudence relies heavily on the premise that "death is different" from other criminal sanctions, and that capital cases entail commensurately demanding standards of reliability. Although invoked most frequently with respect to sentencing, both precedent and logic suggest that heightened reliability applies as well to guilt determination in capital trials. Nevertheless, recurrent and highly visible wrongful convictions in capital cases have affected public opinion, contributed to a precipitous decline in new death sentences, and led to calls for reforms designed to guard against the risk of executing innocent persons. This article examines the implications of the "death is different" doctrine for the problem of wrongful convictions in both capital and non-capital cases. It argues that innovations designed to enhance reliability in the special context of death-penalty prosecutions are important in their own right, but relevant new safeguards also should extend to criminal cases generally, where innocent people are similarly at risk and wrongful convictions are far more prevalent.

  16. Carcinoma of the exocrine pancreas: the histology report.

    PubMed

    Capella, Carlo; Albarello, Luca; Capelli, Paola; Sessa, Fausta; Zamboni, Giuseppe

    2011-03-01

    The Italian Group of Gastrointestinal Pathologists has named a committee to develop recommendations concerning the surgical pathology report for pancreatic cancer. The committee, formed by individuals with special expertise, wrote the recommendations, which were reviewed and approved by council of the Group. The recommendations are divided into several areas including an informative gross description, gross specimen handling, histopathologic diagnosis, immunohistochemistry, molecular findings, and a checklist. The purpose of these recommendations is to provide a fully informative report for the clinician.

  17. Acinar cell carcinoma of exocrine pancreas in two horses.

    PubMed

    de Brot, S; Junge, H; Hilbe, M

    2014-05-01

    Two horses were presented with non-specific clinical signs of several weeks' duration and were humanely destroyed due to a poor prognosis. At necropsy examination, both horses had multiple small, white nodules replacing pancreatic tissue and involving the serosal surface of the abdominal cavity, the liver and the lung. Microscopically, neoplastic cells were organized in acini and contained abundant (case 1) or sparse (horse 2) intracytoplasmic zymogen granules. Immunohistochemically, both tumours expressed amylase and pan-cytokeratin, but not insulin or neuron-specific enolase. In case 2, a low percentage of neoplastic cells expressed glucagon and synaptophysin. The presence of zymogen granules was confirmed in both cases by electron microscopy and occasional fibrillary or glucagon granules were observed in cases 1 and 2, respectively. A diagnosis of pancreatic acinar cell carcinoma was established in both horses.

  18. Opposing roles for SNAP23 in secretion in exocrine and endocrine pancreatic cells.

    PubMed

    Kunii, Masataka; Ohara-Imaizumi, Mica; Takahashi, Noriko; Kobayashi, Masaki; Kawakami, Ryosuke; Kondoh, Yasumitsu; Shimizu, Takeshi; Simizu, Siro; Lin, Bangzhong; Nunomura, Kazuto; Aoyagi, Kyota; Ohno, Mitsuyo; Ohmuraya, Masaki; Sato, Takashi; Yoshimura, Shin-Ichiro; Sato, Ken; Harada, Reiko; Kim, Yoon-Jeong; Osada, Hiroyuki; Nemoto, Tomomi; Kasai, Haruo; Kitamura, Tadahiro; Nagamatsu, Shinya; Harada, Akihiro

    2016-10-10

    The membrane fusion of secretory granules with plasma membranes is crucial for the exocytosis of hormones and enzymes. Secretion disorders can cause various diseases such as diabetes or pancreatitis. Synaptosomal-associated protein 23 (SNAP23), a soluble N-ethyl-maleimide sensitive fusion protein attachment protein receptor (SNARE) molecule, is essential for secretory granule fusion in several cell lines. However, the in vivo functions of SNAP23 in endocrine and exocrine tissues remain unclear. In this study, we show opposing roles for SNAP23 in secretion in pancreatic exocrine and endocrine cells. The loss of SNAP23 in the exocrine and endocrine pancreas resulted in decreased and increased fusion of granules to the plasma membrane after stimulation, respectively. Furthermore, we identified a low molecular weight compound, MF286, that binds specifically to SNAP23 and promotes insulin secretion in mice. Our results demonstrate opposing roles for SNAP23 in the secretion mechanisms of the endocrine and exocrine pancreas and reveal that the SNAP23-binding compound MF286 may be a promising drug for diabetes treatment. © 2016 Kunii et al.

  19. Under Utilization of Pancreas Transplants in Cystic Fibrosis Recipients in the United Network Organ Sharing (UNOS) Data 1987–2014

    PubMed Central

    Usatin, D. J.; Perito, E. R.; Posselt, A. M.; Rosenthal, P.

    2017-01-01

    Despite a high prevalence of pancreatic endocrine and exocrine insufficiency in cystic fibrosis (CF), pancreas transplantation is rarely reported. United Network for Organ Sharing (UNOS) data were used to examine utilization of pancreas transplant and posttransplant outcomes in CF patients. Between 1987–2014, CF patients (N = 4600) underwent 17 liver–pancreas, three lung–pancreas, one liver–lung pancreas, four kidney–pancreas, and three pancreas-only transplants. Of the 303 CF patients who received liver transplantation, 20% had CF-related diabetes (CFRD) before transplantation, and nine of those received a liver–pancreas transplant. Of 4241 CF patients who underwent lung transplantation, 33% had CFRD before transplantation, and three of those received a pancreas transplant. Of 49 CF patients who received a liver–lung transplant, 57% had CFRD before transplantation and one received a pancreas transplant. Posttransplantation diabetes developed in 7% of CF pancreas transplant recipients versus 24% of CF liver and 29% of CF lung recipients. UNOS has no data on pancreas exocrine insufficiency. Two-year post-transplantation survival was 88% after liver–pancreas transplant, 33% after lung–pancreas transplant, and 100% after pancreas–kidney and pancreas-only transplants. Diabetes is common pretransplantation and posttransplantation in CF solid organ transplant recipients, but pancreas transplantation remains rare. Further consideration of pancreas transplant in CF patients undergoing other solid organ transplant may be warranted. PMID:26603034

  20. Annular pancreas

    MedlinePlus

    ... page: //medlineplus.gov/ency/article/001142.htm Annular pancreas To use the sharing features on this page, please enable JavaScript. An annular pancreas is a ring of pancreatic tissue that encircles ...

  1. [Exocrine pancreatic insufficiency (author's transl)].

    PubMed

    Götze, H

    1980-12-01

    Exocrine pancreatic insufficiency usually does not develop before reduction of enzyme output by more than 90%. Patients with pancreatic insufficiency have a ravenous appetite but fail to thrive from malnutrition. The caloric deprivation is primarily due to fat malabsorption, recognized by the passage of bulky foul smelling greasy stools. Several isolated enzyme deficiencies can be separated from diseases with generalised pancreatic insufficiency. Under replacement therapy with pancreatic enzyme supplements most patients improve and gain weight, although fat and bile acid malabsorption are not abolished.

  2. Echovirus 6 Infects Human Exocrine and Endocrine Pancreatic Cells and Induces Pro-Inflammatory Innate Immune Response

    PubMed Central

    Sarmiento, Luis; Frisk, Gun; Anagandula, Mahesh; Hodik, Monika; Barchetta, Ilaria; Netanyah, Eitan; Cabrera-Rode, Eduardo; Cilio, Corrado M.

    2017-01-01

    Human enteroviruses (HEV), especially coxsackievirus serotype B (CVB) and echovirus (E), have been associated with diseases of both the exocrine and endocrine pancreas, but so far evidence on HEV infection in human pancreas has been reported only in islets and ductal cells. This study aimed to investigate the capability of echovirus strains to infect human exocrine and endocrine pancreatic cells. Infection of explanted human islets and exocrine cells with seven field strains of E6 caused cytopathic effect, virus titer increase and production of HEV protein VP1 in both cell types. Virus particles were found in islets and acinar cells infected with E6. No cytopathic effect or infectious progeny production was observed in exocrine cells exposed to the beta cell-tropic strains of E16 and E30. Endocrine cells responded to E6, E16 and E30 by upregulating the transcription of interferon-induced with helicase C domain 1 (IF1H1), 2′-5′-oligoadenylate synthetase 1 (OAS1), interferon-β (IFN-β), chemokine (C–X–C motif) ligand 10 (CXCL10) and chemokine (C–C motif) ligand 5 (CCL5). Echovirus 6, but not E16 or E30, led to increased transcription of these genes in exocrine cells. These data demonstrate for the first time that human exocrine cells represent a target for E6 infection and suggest that certain HEV serotypes can replicate in human pancreatic exocrine cells, while the pancreatic endocrine cells are permissive to a wider range of HEV. PMID:28146100

  3. A pancreatic exocrine-like cell regulatory circuit operating in the upper stomach of the sea urchin Strongylocentrotus purpuratus larva.

    PubMed

    Perillo, Margherita; Wang, Yue Julia; Leach, Steven D; Arnone, Maria Ina

    2016-05-26

    Digestive cells are present in all metazoans and provide the energy necessary for the whole organism. Pancreatic exocrine cells are a unique vertebrate cell type involved in extracellular digestion of a wide range of nutrients. Although the organization and regulation of this cell type is intensively studied in vertebrates, its evolutionary history is still unknown. In order to understand which are the elements that define the pancreatic exocrine phenotype, we have analyzed the expression of genes that contribute to specification and function of this cell-type in an early branching deuterostome, the sea urchin Strongylocentrotus purpuratus. We defined the spatial and temporal expression of sea urchin orthologs of pancreatic exocrine genes and described a unique population of cells clustered in the upper stomach of the sea urchin embryo where exocrine markers are co-expressed. We used a combination of perturbation analysis, drug and feeding experiments and found that in these cells of the sea urchin embryo gene expression and gene regulatory interactions resemble that of bona fide pancreatic exocrine cells. We show that the sea urchin Ptf1a, a key transcriptional activator of digestive enzymes in pancreatic exocrine cells, can substitute for its vertebrate ortholog in activating downstream genes. Collectively, our study is the first to show with molecular tools that defining features of a vertebrate cell-type, the pancreatic exocrine cell, are shared by a non-vertebrate deuterostome. Our results indicate that the functional cell-type unit of the vertebrate pancreas may evolutionarily predate the emergence of the pancreas as a discrete organ. From an evolutionary perspective, these results encourage to further explore the homologs of other vertebrate cell-types in traditional or newly emerging deuterostome systems.

  4. The Pancreas: Causes for Malabsorption

    PubMed Central

    Hackert, Thilo; Schütte, Kerstin; Malfertheiner, Peter

    2014-01-01

    Summary Background The pancreas has a central function in digestion and glucose homeostasis. With regard to the exocrine function, which is responsible for the digestion and absorption of nutrients and vitamins, the most important disturbances of these physiological processes are based on deficiencies in enzyme production and secretion, either due to impaired excretion caused by obstruction of the pancreatic duct or due to loss of pancreatic tissue. Both conditions result in maldigestion, malabsorption, and malnutrition. Methods Systematic literature review. Results Symptoms associated with pancreatic exocrine failure are gastrointestinal discomfort, steatorrhea, and weight loss. Pancreatic exocrine insufficiency caused by ductal obstruction occurs in chronic pancreatitis or with neoplasia of the pancreatic head. Loss of functional parenchyma can be caused either by chronic pancreatitis resulting in fibrotic replacement of the destroyed parenchyma or by a postoperative state of pancreatic resection. Conclusion In patients with chronic pancreatitis, a stage-adapted and timely therapy including conservative as well as surgical measures is essential to prevent functional deterioration and to preserve residual function. In the case of pancreatic resection for chronic pancreatitis, this can be achieved with modern organ-sparing surgery such as the duodenum-preserving pancreatic head resection. In patients requiring more extended pancreatic resections and even total duodenopancreatectomy, regardless of the underlying indication, adequate enzyme replacement and monitoring of the nutritional status is critical to prevent impairment of quality of life as well as detrimental malnutrition in the long term. PMID:26288593

  5. Immunodetection of cocaine- and amphetamine-regulated transcript in bovine pancreas.

    PubMed

    Janiuk, Izabela; Młynek, Krzysztof

    2015-07-01

    This study was aimed at identifying and determining the configuration of structures which contain the cocaine- and amphetamine-regulated transcript peptide (CART) in the bovine pancreas. The study material was collected from 20 animals. The distribution of CART in the bovine pancreas was investigated, by an immunohistochemical evaluation. CART peptide in the normal pancreas has been identified in intrapancreatic ganglia, nerve fibres and in endocrine cells of Langerhans islets and exocrine pancreas. CART immunoreactive nerve fibres innervate the exocrine and endocrine regions and the intrapancreatic ganglia, where they form a moderate number of networks, encircling the cell bodies. The few CART-immunoreactive endocrine cells, that appear in the bovine pancreas, are not limited to the islet cells, where they form a subpopulation of CART-containing cells, but are also individually distributed in the exocrine region. Furthermore, CART has been visualized in nerve fibres, innervating pancreatic outlet ducts and blood vessels. CART plays a physiological role in the integrated mechanisms that regulate both endocrine and exocrine pancreatic secretion. These results are consistent with the hypothesis that CART expression in nerve fibres and intrapancreatic ganglia is a common feature of the mammalian pancreas, whereas its expression in endocrine cells appears to be restricted to single cells of the bovine pancreas. Copyright © 2015 Elsevier GmbH. All rights reserved.

  6. Pancreas Transplantation

    PubMed Central

    Sutherland, David ER

    2010-01-01

    Diabetes mellitus is generally treated with oral diabetic drugs and/or insulin. However, the morbidity and mortality associated with this condition increases over time, even in patients receiving intensive insulin treatment, and this is largely attributable to diabetic complications or the insulin therapy itself. Pancreas transplantation in humans was first conducted in 1966, since when there has been much debate regarding the legitimacy of this procedure. Technical refinements and the development of better immunosuppressants and better postoperative care have brought about marked improvements in patient and graft survival and a reduction in postoperative morbidity. Consequently, pancreas transplantation has become the curative treatment modality for diabetes, particularly for type I diabetes. An overview of pancreas transplantation is provided herein, covering the history of pancreas transplantation, indications for transplantation, cadaveric and living donors, surgical techniques, immunosuppressants, and outcome following pancreas transplantation. The impact of successful pancreas transplantation on the complications of diabetes will also be reviewed briefly. PMID:21253293

  7. Chronic metabolic acidosis destroys pancreas.

    PubMed

    Melamed, Peter; Melamed, Felix

    2014-11-28

    One primary reason for the current epidemic of digestive disorders might be chronic metabolic acidosis, which is extremely common in the modern population. Chronic metabolic acidosis primarily affects two alkaline digestive glands, the liver, and the pancreas, which produce alkaline bile and pancreatic juice with a large amount of bicarbonate. Even small acidic alterations in the bile and pancreatic juice pH can lead to serious biochemical/biomechanical changes. The pancreatic digestive enzymes require an alkaline milieu for proper function, and lowering the pH disables their activity. It can be the primary cause of indigestion. Acidification of the pancreatic juice decreases its antimicrobial activity, which can lead to intestinal dysbiosis. Lowering the pH of the pancreatic juice can cause premature activation of the proteases inside the pancreas with the potential development of pancreatitis. The acidification of bile causes precipitation of the bile acids, which irritate the entire biliary system and create bile stone formation. Aggressive mixture of the acidic bile and the pancreatic juice can cause erratic contractions of the duodenum's walls and subsequent bile reflux into the stomach and the esophagus. Normal exocrine pancreatic function is the core of proper digestion. Currently, there is no effective and safe treatment for enhancing the exocrine pancreatic function. Restoring normal acid-base homeostasis can be a useful tool for pathophysiological therapeutic approaches for various gastrointestinal disorders. There is strong research and practical evidence that restoring the HCO3(-) capacity in the blood can improve digestion.

  8. Control of cell identity in pancreas development and regeneration.

    PubMed

    Stanger, Ben Z; Hebrok, Matthias

    2013-06-01

    The endocrine and exocrine cells in the adult pancreas are not static, but can change their differentiation state in response to injury or stress. This concept of cells in flux means that there may be ways to generate certain types of cells (such as insulin-producing β-cells) and prevent formation of others (such as transformed neoplastic cells). We review different aspects of cell identity in the pancreas, discussing how cells achieve their identity during embryonic development and maturation, and how this identity remains plastic, even in the adult pancreas.

  9. Morphometric Study of Pancreas in Human Fetuses

    PubMed Central

    Dhende, Abhijeet S.; Joshi, Deepak S.

    2016-01-01

    Introduction The pancreas arises from the endoderm as a dorsal and a ventral bud which fuse together to form the single organ. It extends transversely across the posterior abdominal wall from the duodenum to the spleen. Functionally, it is endocrine and exocrine. Aim This study was undertaken to study the morphometry of human pancreas at different gestational age groups of normal, still born fetuses. Materials and Methods Forty aborted human fetuses (25 male and 15 female) of 12-40 weeks gestational age with no obvious congenital abnormality were obtained. The fetuses were dissected and pancreas was removed. The length and weight of the pancreas as well as height of its head were noted. Results It was observed that there was increase in body weight and crown rump length with increasing gestational age. The average length of pancreas was 1.80 cm in 12th week and 4.70 cm in 40th week of gestation. The average height of pancreas head was 0.80 cm in the 12th and 2.70 cm in 40th week of gestation. Conclusion The knowledge of development of pancreas helps in planning new therapeutic interventions in the treatment of various congenital and functional pancreatic anomalies. PMID:28050352

  10. Eyewitness identification evidence and innocence risk.

    PubMed

    Clark, Steven E; Godfrey, Ryan D

    2009-02-01

    It is well known that the frailties of human memory and vulnerability to suggestion lead to eyewitness identification errors. However, variations in different aspects of the eyewitnessing conditions produce different kinds of errors that are related to wrongful convictions in very different ways. We present a review of the eyewitness identification literature, organized around underlying cognitive mechanisms, memory, similarity, and decision processes, assessing the effects on both correct and mistaken identification. In addition, we calculate a conditional probability we call innocence risk, which is the probability that the suspect is innocent, given that the suspect was identified. Assessment of innocence risk is critical to the theoretical development of eyewitness identification research, as well as to legal decision making and policy evaluation. Our review shows a complex relationship between misidentification and innocence risk, sheds light on some areas of controversy, and suggests that some issues thought to be resolved are in need of additional research.

  11. The epistemic innocence of psychedelic states.

    PubMed

    Letheby, Chris

    2016-01-01

    One recent development in epistemology, the philosophical study of knowledge, is the notion of 'epistemic innocence' introduced by Bortolotti and colleagues. This concept expresses the idea that certain suboptimal cognitive processes may nonetheless have epistemic (knowledge-related) benefits. The idea that delusion or confabulation may have psychological benefits is familiar enough. What is novel and interesting is the idea that such conditions may also yield significant and otherwise unavailable epistemic benefits. I apply the notion of epistemic innocence to research on the transformative potential of psychedelic drugs. The popular epithet 'hallucinogen' exemplifies a view of these substances as fundamentally epistemically detrimental. I argue that the picture is more complicated and that some psychedelic states can be epistemically innocent. This conclusion is highly relevant to policy debates about psychedelic therapy. Moreover, analysing the case of psychedelics can shed further light on the concept of epistemic innocence itself. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Hippo Signaling Regulates Pancreas Development through Inactivation of Yap

    PubMed Central

    Day, Caroline E.; Boerner, Brian P.; Johnson, Randy L.; Sarvetnick, Nora E.

    2012-01-01

    The mammalian pancreas is required for normal metabolism, with defects in this vital organ commonly observed in cancer and diabetes. Development must therefore be tightly controlled in order to produce a pancreas of correct size, cell type composition, and physiologic function. Through negative regulation of Yap-dependent proliferation, the Hippo kinase cascade is a critical regulator of organ growth. To investigate the role of Hippo signaling in pancreas biology, we deleted Hippo pathway components in the developing mouse pancreas. Unexpectedly, the pancreas from Hippo-deficient offspring was reduced in size, with defects evident throughout the organ. Increases in the dephosphorylated nuclear form of Yap are apparent throughout the exocrine compartment and correlate with increases in levels of cell proliferation. However, the mutant exocrine tissue displays extensive disorganization leading to pancreatitis-like autodigestion. Interestingly, our results suggest that Hippo signaling does not directly regulate the pancreas endocrine compartment as Yap expression is lost following endocrine specification through a Hippo-independent mechanism. Altogether, our results demonstrate that Hippo signaling plays a crucial role in pancreas development and provide novel routes to a better understanding of pathological conditions that affect this organ. PMID:23071096

  13. Using pancreas tissue slices for in situ studies of islet of Langerhans and acinar cell biology.

    PubMed

    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. Pancreas development is promoted by cyclopamine, a hedgehog signaling inhibitor.

    PubMed

    Kim, S K; Melton, D A

    1998-10-27

    Exposure to cyclopamine, a steroid alkaloid that blocks Sonic hedgehog (Shh) signaling, promotes pancreatic expansion in embryonic chicks. Heterotopic development of pancreatic endocrine and exocrine structures occurs in regions adjacent to the pancreas including stomach and duodenum, and insulin-producing islets in the pancreas are enlarged. The homeodomain transcription factor PDX1, required for pancreas development, is expressed broadly in the posterior foregut but pancreas development normally initiates only in a restricted region of PDX1-expressing posterior foregut where endodermal Shh expression is repressed. The results suggests that cyclopamine expands the endodermal region where Shh signaling does not occur, resulting in pancreatic differentiation in a larger region of PDX1-expressing foregut endoderm. Cyclopamine reveals the capacity of a broad region of the posterior embryonic foregut to form pancreatic cells and provides a means for expanding embryonic pancreas development.

  15. Gravity in mammalian organ development: differentiation of cultured lung and pancreas rudiments during spaceflight

    NASA Technical Reports Server (NTRS)

    Spooner, B. S.; Hardman, P.; Paulsen, A.

    1994-01-01

    Organ culture of embryonic mouse lung and pancreas rudiments has been used to investigate development and differentiation, and to assess the effects of microgravity on culture differentiation, during orbital spaceflight of the shuttle Endeavour (mission STS-54). Lung rudiments continue to grow and branch during spaceflight, an initial result that should allow future detailed study of lung morphogenesis in microgravity. Cultured embryonic pancreas undergoes characteristic exocrine acinar tissue and endocrine islet tissue differentiation during spaceflight, and in ground controls. The rudiments developing in the microgravity environment of spaceflight appear to grow larger than their ground counterparts, and they may have differentiated more rapidly than controls, as judged by exocrine zymogen granule presence.

  16. Gravity in mammalian organ development: differentiation of cultured lung and pancreas rudiments during spaceflight

    NASA Technical Reports Server (NTRS)

    Spooner, B. S.; Hardman, P.; Paulsen, A.

    1994-01-01

    Organ culture of embryonic mouse lung and pancreas rudiments has been used to investigate development and differentiation, and to assess the effects of microgravity on culture differentiation, during orbital spaceflight of the shuttle Endeavour (mission STS-54). Lung rudiments continue to grow and branch during spaceflight, an initial result that should allow future detailed study of lung morphogenesis in microgravity. Cultured embryonic pancreas undergoes characteristic exocrine acinar tissue and endocrine islet tissue differentiation during spaceflight, and in ground controls. The rudiments developing in the microgravity environment of spaceflight appear to grow larger than their ground counterparts, and they may have differentiated more rapidly than controls, as judged by exocrine zymogen granule presence.

  17. Artifical Pancreas

    NASA Astrophysics Data System (ADS)

    Fei, Jiangfeng

    2013-03-01

    In 2006, JDRF launched the Artificial Pancreas Project (APP) to accelerate the development of a commercially-viable artificial pancreas system to closely mimic the biological function of the pancreas individuals with insulin-dependent diabetes, particularly type 1 diabetes. By automating detection of blood sugar levels and delivery of insulin in response to those levels, an artificial pancreas has the potential to transform the lives of people with type 1 diabetes. The 6-step APP development pathway serves as JDRF's APP strategic funding plan and defines the priorities of product research and development. Each step in the plan represents incremental advances in automation beginning with devices that shut off insulin delivery to prevent episodes of low blood sugar and progressing ultimately to a fully automated ``closed loop'' system that maintains blood glucose at a target level without the need to bolus for meals or adjust for exercise.

  18. Pancreas Transplantation

    MedlinePlus

    ... for Association Events Messaging Tools Recruiting Advocates Local Market Planning Training Webinars News & Events Advocacy News Call ... risky. Each person needs to carefully weigh the potential benefits and risks. Benefits of Pancreas Transplants You ...

  19. Pancreas divisum

    MedlinePlus

    ... it. Alternative Names Pancreatic divisum Images Digestive system Endocrine glands Pancreas References Forsmark CE. Pancreatitis. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 25th ed. Philadelphia, PA: Elsevier Saunders; 2016:chap ...

  20. Pancreas transplant

    MedlinePlus

    ... In: Cameron JL, Cameron AM, eds. Current Surgical Therapy . 11th ed. Philadelphia, PA: Elsevier Saunders; 2014:511-5. Gruessner AC, Gruessner RWG. Pancreas and kidney transplantation for diabetic nephropathy. In: Morris PJ, Knechtle SJ, eds. Kidney Transplantation: ...

  1. Considerations on pancreatic exocrine function after pancreaticoduodenectomy.

    PubMed

    Morera-Ocon, Francisco José; Sabater-Orti, Luis; Muñoz-Forner, Elena; Pérez-Griera, Jaime; Ortega-Serrano, Joaquín

    2014-09-15

    The pancreaticoduodenectomy (PD) procedure may lead to pancreatic exocrine and endocrine insufficiency. There are several types of reconstruction for this kind of operation. Pancreaticogastrostomy (PG) was introduced to reduce the rate of postoperative pancreatic fistula. Although some randomized control trials have shown no differences regarding pancreatic leakage between PG and pancreaticojejunostomy (PJ), recently some reports reveal benefits from the PG over the PJ. Some surgeons concern about the performing of the PG and inactivation of pancreatic enzymes being in contact with the gastric juice, and the detrimental results over the exocrine pancreatic function. The pancreatic exocrine function can be measured with direct and indirect tests. Direct tests have the highest sensitivity and specificity for detection of exocrine insufficiency but require tube placement. Among the tubeless indirect tests, the van de Kamer stool fat analysis remains the standard to diagnose fat malabsorption. The patient compliance and time consuming makes it not so suitable for its clinical use. Fecal immunoreactive elastase test is employed for screening of exocrine insufficiency, is not cumbersome, and has been used to study pancreatic function after resection. We analyze the FE1 levels in our patients after the PD with two types of reconstruction, PG and PJ, and we discuss some considerations about the pancreaticointestinal drainage method after pancreaticoduodenectomy.

  2. Organ Facts: Kidney / Pancreas

    MedlinePlus

    ... Lung Kidney Pancreas Kidney/Pancreas Liver Intestine Kidney/Pancreas Facts The kidneys are a pair of reddish- ... the chemical (electrolyte) composition of the blood. The pancreas is a five to six inch gland located ...

  3. Exocrine pancreatic insufficiency following esophagectomy.

    PubMed

    Huddy, J R; Macharg, F M S; Lawn, A M; Preston, S R

    2013-08-01

    Weight loss following esophagectomy is a management challenge for all patients. It is multifactorial with contributing factors including loss of gastric reservoir, rapid small bowel transit, malabsorption, and adjuvant chemotherapy. The development of a postoperative malabsorption syndrome, as a result of exocrine pancreatic insufficiency (EPI), is recognized in a subgroup of patients following gastrectomy. This has not previously been documented following esophageal resection. EPI can result in symptoms of flatulence, diarrhea, steatorrhea, vitamin deficiencies, and weight loss. It therefore has the potential to pose a significant level of morbidity in postoperative patients. There is some evidence that patients with proven EPI (fecal elastase-1 < 200 μg/g) may benefit from a trial of pancreatic enzyme replacement therapy (PERT). We observed symptoms compatible with EPI in a subgroup of patients following esophagectomy. We hypothesized that this was contributing to malabsorption and malnutrition in these patients. To investigate this, fecal elastase-1 was measured in postoperative patients, and in those with proven EPI, a trial of PERT was commenced in combination with specialist dietary education. At routine postoperative follow-up, which included assessment by a specialist dietitian, those patients with symptoms suggestive of malabsorption were given the opportunity to have their fecal elastase-1 measured. PERT was then offered to patients with fecal elastase-1 less than 200 μg/g (EPI) as well as those in the 200-500 μg/g range (mild EPI) with more severe symptoms. Fecal elastase-1 was measured in 63 patients between June 2009 and January 2011 at a median of 4 months (range 1-42) following surgery. Ten patients had fecal elastase-1 less than 200 μg/g, and all had failed to maintain preoperative weight. All accepted a trial of PERT. Nine (90%) had symptomatic improvement, and seven (70%) increased their weight. Thirty-nine patients had a fecal elastase-1 in

  4. Solid pseudopapillary tumor of the pancreas.

    PubMed

    Schlarb, Haley C; Schlarb, Alexander C; Ubert, H Adam; Schlarb, Christopher A

    2015-01-01

    Solid pseudopapillary tumor is a rare tumor accounting for 1-2% of exocrine neoplasms involving the pancreas. This typically benign tumor is predominately found in young females of non-Caucasian descent between the second and fourth decades of life. Despite the reported increasing incidence of this neoplasm, many physicians are unfamiliar with this tumor, which may lead to uncertainty of diagnosis and treatment. While further delineating the clinical and imaging features of this tumor, we present two cases with review of the literature.

  5. Implication of epigenetics in pancreas development and disease.

    PubMed

    Quilichini, Evans; Haumaitre, Cécile

    2015-12-01

    Pancreas development is controlled by a complex interaction of signaling pathways and transcription factor networks that determine pancreatic specification and differentiation of exocrine and endocrine cells. Epigenetics adds a new layer of gene regulation. DNA methylation, histone modifications and non-coding RNAs recently appeared as important epigenetic factors regulating pancreas development. In this review, we report recent findings obtained by analyses in model organisms as well as genome-wide approaches that demonstrate the role of these epigenetic regulators in the control of exocrine and endocrine cell differentiation, identity, function, proliferation and regeneration. We also highlight how altered epigenetic processes contribute to pancreatic disorders: diabetes and pancreatic cancer. Uncovering these epigenetic events can help to better understand these diseases, provide novel therapeutical targets for their treatment, and improve cell-based therapies for diabetes.

  6. The case for pancreas after kidney transplantation.

    PubMed

    Fridell, Jonathan A; Mangus, Richard S; Hollinger, Edward F; Taber, Tim E; Goble, Michelle L; Mohler, Elaine; Milgrom, Martin L; Powelson, John A

    2009-01-01

    Pancreas after kidney (PAK) transplantation has historically demonstrated inferior pancreas allograft survival compared to simultaneous pancreas and kidney (SPK) transplantation. Under our current immunosuppression protocol, we have noted excellent outcomes and rare immunological graft loss. The goal of this study was to compare pancreas allograft survival in PAK and SPK recipients using this regimen. This was a single center retrospective review of all SPK and PAK transplants performed between January 2003 and November 2007. All transplants were performed with systemic venous drainage and enteric exocrine drainage. Immunosuppression included induction with rabbit anti-thymocyte globulin (thymoglobulin), early steroid withdrawal, and maintenance with tacrolimus and sirolimus or mycophenolate mofetil. Study end points included graft and patient survival and immunosuppression related complications. Transplants included PAK 61 (30%) and SPK 142 (70%). One-yr patient survival was PAK 98% and SPK 95% (p = 0.44) and pancreas graft survival was PAK 95% and SPK 90% (p = 0.28). Acute cellular rejection was uncommon with 2% requiring treatment in each group. Survival for PAK using thymoglobulin induction, early steroid withdrawal and tacrolimus-based immunosuppression is at least comparable to SPK and should be pursued in the recipient with a potential living donor.

  7. [Historical course of surgical techniques in pancreas transplantation].

    PubMed

    Toledo-Pereyra, L H; Rodríguez, F J

    1994-01-01

    Since the original description of the pancreas transplant technique in animals, initially as a pedicle transplant in 1892, free graft in 1913, and then as a vascularized organ in 1927, there have been several changes in the handling of the exocrine secretions, as well as the vascular anastomoses, and the posttransplant function in relation to the immunosuppressive therapy. The surgical technical changes have included the ligature of the duct, the free drainage to the abdominal cavity, the pancreas transplant with a duodenal segment, the chemical occlusion of the duct, and its drainage to the intestine or to the bladder with a duodenal segment. This last technique remains as the standard technique currently used for pancreas transplantation, along with the combined transplant of the kidney. This work reviews the historical aspects, the evolution of the experimental and clinical surgical techniques, and the current results associated with the surgical management of pancreas transplantation.

  8. Case report. Acinar cell carcinoma with fatty change arising from the pancreas.

    PubMed

    Chung, W-S; Park, M-S; Kim, D W; Kim, K W

    2011-12-01

    Acinar cell carcinoma of the pancreas is a rare malignant tumour developing from acinar cells, accounting for approximately 1% of pancreatic exocrine tumours. We experienced a case of an acinar cell carcinoma with fatty change. To the best of our knowledge, this is the first case report of an acinar cell carcinoma with fatty change in the clinical literature.

  9. Pancreatic neuroendocrine carcinoma with exocrine differentiation in a young cat.

    PubMed

    Michishita, Masaki; Takagi, Mariko; Kishimoto, Takuya E; Nakahira, Rei; Nogami, Takeshi; Yoshimura, Hisashi; Hatakeyama, Hitoshi; Azakami, Daigo; Ochiai, Kazuhiko; Takahashi, Kimimasa

    2017-05-01

    A 35-mo-old spayed female mixed-breed cat with continuous vomiting, emaciation, and abdominal distention for 2 wk was presented to a private veterinary clinic for evaluation. At 71 d after the initial visit, the cat died with anemia, jaundice, and hypoalbuminemia, and was subjected to autopsy. Grossly, numerous firm masses, 0.5-2.5 cm diameter, were randomly located in the left lobe of the pancreas. Histologic examination revealed that the pancreatic mass consisted of 2 tumor cell types: mostly small round cells with a minority of epithelial cells. The small cells were arranged in nests of various sizes, which were separated by thin fibrous stroma, and had small, round, hyperchromatic nuclei, scant cytoplasm containing argyrophilic granules, and often formed rosettes. The epithelial cells formed luminal structures. Metastases were observed in the liver, greater omentum, and pancreatic, gastric, pulmonary, and mediastinal lymph nodes. Immunohistochemical examination revealed that the small cells were positive for vimentin, neuron-specific enolase, chromogranin A, cytokeratin (CK) AE1/AE3, and trypsin, whereas the epithelial cells were positive for AE1/AE3, trypsin, CK19, and nestin. Ultrastructurally, the small cells contained abundant electron-dense granules, ~200 nm diameter, whereas the epithelial cells had apical microvilli and numerous zymogen granules, ~300 nm diameter. These findings indicated that the tumor was a pancreatic neuroendocrine carcinoma with exocrine differentiation and systemic metastases.

  10. Evaluation of Biochemical Markers Serum Amylase and Serum Lipase for the Assessment of Pancreatic Exocrine Function in Diabetes Mellitus

    PubMed Central

    Iyer, Chandrashekhar M; Madivalar, Mamatha Thimmanna; Wadde, Satish Kishanrao; Howale, Deepak Sadashiv

    2016-01-01

    Introduction Diabetes mellitus (DM), a metabolic disorder characterized by hyperglycaemia, associated with deficiency or resistance to insulin indicates endocrinal abnormality of the pancreas. Amylase and lipase are enzymes secreted by the exocrine portion of the pancreas. Endocrinal derangement observed in diabetes may interfere with the exocrine function of the pancreas. Aim To estimate the levels of fasting blood sugar, serum lipase, serum amylase in patients of type 1 and type 2 DM. Than comparing them with healthy controls and to study the effect of type 1 and type 2 DM on pancreatic exocrine function using serum levels of amylase and lipase as biochemical marker. Materials and Methods This study was conducted at GMERS Medical College and Hospital from Dec 2015 to July 2016. Thirty patients of type 1 DM and 30 patients of type 2 DM, who were already diagnosed and taking treatment, were included in this study. A total number of 30 apparently healthy individuals were recruited as the control group in our study. Fasting venous blood samples were collected from the cases as well as the controls and they were analysed by using semi auto analyser for blood glucose, serum amylase and serum lipase. The results were analysed statistically by using SPSS software. Values were expressed as means ± SD. Results We found statistically significant (p<0.01) low values for serum amylase and serum lipase in patients with type 1 and type 2 DM as compared to healthy controls. Fasting blood sugar was significantly higher in cases as compared to controls. We found negative correlation of fasting blood sugar level with serum amylase and serum lipase and positive correlation of serum amylase with serum lipase in both type 1 and type 2 DM. Conclusion Our study clearly demonstrated that in type 1 and type 2 DM, there was increase in fasting blood sugar with decrease in serum amylase and serum lipase which signifies the derangement of endocrine-exocrine axis of the pancreas. Serum

  11. Proliferative response of different exocrine pancreatic cell types to hormonal stimuli. I. Effects of long-term cerulein administration.

    PubMed

    Gasslander, T; Smeds, S; Blomqvist, L; Ihse, I

    1990-11-01

    The trophic effect on the exocrine pancreas of the cholecystokinin analogue cerulein was studied in a long-term experiment (20 or 160 micrograms/kg/24 h for 14 days) in mice by measuring changes in pancreatic weight and protein, amylase, and DNA content. Further, the selective cell growth stimulation exerted by various doses of cerulein (4, 20, 54, 160 micrograms/kg/24 h) on different exocrine pancreatic cell types was studied by continuous administration of 3H-thymidine. In the first experiment animals given 20 micrograms/kg/24 h of cerulein had increased pancreatic weight and amylase and protein content, whereas the animals given the higher dose had unchanged weight and a less pronounced increase in amylase and protein content. The pancreatic DNA content was unaffected in the 20-micrograms group but was clearly decreased by the higher dose. In the second experiment a statistically significant increase over controls was found in the fraction of labeled ductal cells when 20, 54, and 160 micrograms of cerulein was administered. However, in the acinar cell population an increase was measured only in the 160-micrograms group. A tendency to nadir in cell labeling was observed in both acinar and ductal cell groups at less stimulation. Labeling of centroacinar cells increased in all cerulein-treated groups. The results show that all cell types of the exocrine pancreas can be forced into proliferation by the cholecystokinin analogue used and that there is preferential cell growth stimulation in the ductal and centroacinar cell populations.

  12. Pancreatic stellate cells--multi-functional cells in the pancreas.

    PubMed

    Masamune, Atsushi; Shimosegawa, Tooru

    2013-01-01

    There is accumulating evidence that activated pancreatic stellate cells (PSCs) play a pivotal role in pancreatic fibrosis in chronic pancreatitis and pancreatic cancer. In addition, we have seen great progress in our understanding of the cell biology of PSCs and the interactions between PSCs and other cell types in the pancreas. In response to pancreatic injury or inflammation, quiescent PSCs are activated to myofibroblast-like cells. Recent studies have shown that the activation of intracellular signaling pathways such as mitogen-activated protein kinases plays a role in the activation of PSCs. microRNAs might also play a role, because the microRNA expression profiles are dramatically altered in the process of activation. In addition to producing extracellular matrix components such as type I collagen, PSCs have a wide variety of cell functions related to local immunity, inflammation, angiogenesis, and exocrine and endocrine functions in the pancreas. From this point of view, the interactions between PSCs and other cell types such as pancreatic exocrine cells, endocrine cells, and cancer cells have attracted increasing attention of researchers. PSCs might regulate exocrine functions in the pancreas through the cholecystokinin-induced release of acetylcholine. PSCs induce apoptosis and decrease insulin expression in β-cells, suggesting a novel mechanism of diabetes in diseased pancreas. PSCs promote the progression of pancreatic cancer by multiple mechanisms. Recent studies have shown that PSCs induce epithelial-mesenchymal transition and enhance the stem-cell like features of pancreatic cancer cells. In conclusion, PSCs should now be recognized as not only profibrogenic cells but as multi-functional cells in the pancreas.

  13. CERCLA's innocent landowner defense -- Consultants beware

    SciTech Connect

    Nijman, J.T. )

    1994-05-01

    Consultant liability is an area of the innocent landowner defense under CERCLA that is not often discussed. The only reasonable way to protect consultants hired by innocent purchasers'' is for Congress or state legislatures to establish standardized, regulated audit guidelines. However, even standardized guidelines do not protect consultants completely, because standards cannot specify all activity necessary to perform a particular task. Each project has unique circumstances, and standards arguably can become per se determinants of liability. CERCLA provides three defenses to its basic strict, joint and several liability provisions -- an act of God, an act of war, and an act or omission of a third party not in a contractual relationship with the current owner. Congress amended the third-party not in a contractual relationship with the current owner. Congress amended the third-party defense in SARA by redefining contractual relationship'' to exclude from liability owners who acquired the real property following disposal or placement of hazardous material, and established satisfactorily that the owner at the time of purchase neither knew nor had reason to know hazardous substances were disposed on the property -- the innocent landowner defense.

  14. Exocrine Pancreatic Carcinogenesis and Autotaxin Expression

    PubMed Central

    Kadekar, Sandeep; Silins, Ilona; Korhonen, Anna; Dreij, Kristian; Al-Anati, Lauy; Högberg, Johan; Stenius, Ulla

    2012-01-01

    Exocrine pancreatic cancer is an aggressive disease with an exceptionally high mortality rate. Genetic analysis suggests a causative role for environmental factors, but consistent epidemiological support is scarce and no biomarkers for monitoring the effects of chemical pancreatic carcinogens are available. With the objective to identify common traits for chemicals inducing pancreatic tumors we studied the National Toxicology Program (NTP) bioassay database. We found that male rats were affected more often than female rats and identified eight chemicals that induced exocrine pancreatic tumors in males only. For a hypothesis generating process we used a text mining tool to analyse published literature for suggested mode of actions (MOA). The resulting MOA analysis suggested inflammatory responses as common feature. In cell studies we found that all the chemicals increased protein levels of the inflammatory protein autotaxin (ATX) in Panc-1, MIA PaCa-2 or Capan-2 cells. Induction of MMP-9 and increased invasive migration were also frequent effects, consistent with ATX activation. Testosterone has previously been implicated in pancreatic carcinogenesis and we found that it increased ATX levels. Our data show that ATX is a target for chemicals inducing pancreatic tumors in rats. Several lines of evidence implicate ATX and its product lysophosphatidic acid in human pancreatic cancer. Mechanisms of action may include stimulated invasive growth and metastasis. ATX may interact with hormones or onco- or suppressor-genes often deregulated in exocrine pancreatic cancer. Our data suggest that ATX is a target for chemicals promoting pancreatic tumor development. PMID:22952646

  15. National Pancreas Foundation

    MedlinePlus

    ... NPF Centers Animated Pancreas Patient About the Pancreas Pancreatic Cancer Chronic Pancreatitis Acute Pancreatitis Children/Pediatric Other Pancreas ... Providing hope to those suffering from pancreatitis and pancreatic cancer. Support Pancreatic Research Slide2 Providing hope to those ...

  16. Normal Pancreas Anatomy

    MedlinePlus

    ... e.g. -historical Searches are case-insensitive Pancreas Anatomy Add to My Pictures View /Download : Small: 761x736 ... View Download Large: 3172x3068 View Download Title: Pancreas Anatomy Description: Anatomy of the pancreas; drawing shows the ...

  17. Acidic duodenal pH alters gene expression in the cystic fibrosis mouse pancreas.

    PubMed

    Kaur, Simran; Norkina, Oxana; Ziemer, Donna; Samuelson, Linda C; De Lisle, Robert C

    2004-08-01

    The duodenum is abnormally acidic in cystic fibrosis (CF) due to decreased bicarbonate ion secretion that is dependent on the CF gene product CFTR. In the CFTR null mouse, the acidic duodenum results in increased signaling from the intestine to the exocrine pancreas in an attempt to stimulate pancreatic bicarbonate ion secretion. Excess stimulation is proposed to add to the stress/inflammation of the pancreas in CF. DNA microarray analysis of the CF mouse revealed altered pancreatic gene expression characteristic of stress/inflammation. When the duodenal pH was corrected genetically (crossing CFTR null with gastrin null mice) or pharmacologically (use of the proton pump inhibitor omeprazole), expression levels of genes measured by quantitative RT-PCR were significantly normalized. It is concluded that the acidic duodenal pH in CF contributes to the stress on the exocrine pancreas and that normalizing duodenal pH reduces this stress.

  18. Telocytes in pancreas of the Chinese giant salamander (Andrias davidianus).

    PubMed

    Zhang, Hui; Yu, Pengcheng; Zhong, Shengwei; Ge, Tingting; Peng, Shasha; Guo, Xiaoquan; Zhou, Zuohong

    2016-11-01

    Telocytes (TCs), novel interstitial cells, have been identified in various organs of many mammals. However, information about TCs of lower animals remains rare. Herein, pancreatic TCs of the Chinese giant salamanders (Andrias davidianus) were identified by CD34 immunohistochemistry (IHC) and transmission electron microscopy (TEM). The IHC micrographs revealed CD34(+) TCs with long telopodes (Tps) that were located in the interstitium of the pancreas. CD34(+) TCs/Tps were frequently observed between exocrine acinar cells and were close to blood vessels. The TEM micrographs also showed the existence of TCs in the interstitium of the pancreas. TCs had distinctive ultrastructural features, such as one to three very long and thin Tps with podoms and podomers, caveolae, dichotomous branching, neighbouring exosomes and vesicles. The Tps and exosomes were found in close proximity to exocrine acinar cells and α cells. It is suggested that TCs may play a role in the regeneration of acinar cells and α cells. In conclusion, our results demonstrated the presence of TCs in the pancreas of the Chinese giant salamander. This finding will assist us in a better understanding of TCs functions in the amphibian pancreas. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  19. Use of the Electronic Medical Record to Assess Pancreas Size in Type 1 Diabetes

    PubMed Central

    Virostko, John; Hilmes, Melissa; Eitel, Kelsey; Moore, Daniel J.; Powers, Alvin C.

    2016-01-01

    Aims This study harnessed the electronic medical record to assess pancreas volume in patients with type 1 diabetes (T1D) and matched controls to determine whether pancreas volume is altered in T1D and identify covariates that influence pancreas volume. Methods This study included 25 patients with T1D and 25 age-, sex-, and weight-matched controls from the Vanderbilt University Medical Center enterprise data warehouse. Measurements of pancreas volume were made from medical imaging studies using magnetic resonance imaging (MRI) or computed tomography (CT). Results Patients with T1D had a pancreas volume 47% smaller than matched controls (41.16 ml vs. 77.77 ml, P < 0.0001) as well as pancreas volume normalized by subject body weight, body mass index, or body surface area (all P < 0.0001). Pancreatic volume was smaller with a longer duration of T1D across the patient population (N = 25, P = 0.04). Additionally, four individual patients receiving multiple imaging scans displayed progressive declines in pancreas volume over time (~ 6% of volume/year), whereas five controls scanned a year apart did not exhibit a decline in pancreas size (P = 0.03). The pancreas was uniformly smaller on the right and left side of the abdomen. Conclusions Pancreas volume declines with disease duration in patients with T1D, suggesting a protracted pathological process that may include the exocrine pancreas. PMID:27391588

  20. Use of the Electronic Medical Record to Assess Pancreas Size in Type 1 Diabetes.

    PubMed

    Virostko, John; Hilmes, Melissa; Eitel, Kelsey; Moore, Daniel J; Powers, Alvin C

    2016-01-01

    This study harnessed the electronic medical record to assess pancreas volume in patients with type 1 diabetes (T1D) and matched controls to determine whether pancreas volume is altered in T1D and identify covariates that influence pancreas volume. This study included 25 patients with T1D and 25 age-, sex-, and weight-matched controls from the Vanderbilt University Medical Center enterprise data warehouse. Measurements of pancreas volume were made from medical imaging studies using magnetic resonance imaging (MRI) or computed tomography (CT). Patients with T1D had a pancreas volume 47% smaller than matched controls (41.16 ml vs. 77.77 ml, P < 0.0001) as well as pancreas volume normalized by subject body weight, body mass index, or body surface area (all P < 0.0001). Pancreatic volume was smaller with a longer duration of T1D across the patient population (N = 25, P = 0.04). Additionally, four individual patients receiving multiple imaging scans displayed progressive declines in pancreas volume over time (~ 6% of volume/year), whereas five controls scanned a year apart did not exhibit a decline in pancreas size (P = 0.03). The pancreas was uniformly smaller on the right and left side of the abdomen. Pancreas volume declines with disease duration in patients with T1D, suggesting a protracted pathological process that may include the exocrine pancreas.

  1. Ultrastructural and immunohistochemical analysis of the 8-20 week human fetal pancreas

    PubMed Central

    Riopel, Matthew; Li, Jinming; Fellows, George F; Goodyer, Cynthia G; Wang, Rennian

    2014-01-01

    Development of the human pancreas is well-known to involve tightly controlled differentiation of pancreatic precursors to mature cells that express endocrine- or exocrine-specific protein products. However, details of human pancreatic development at the ultrastructural level are limited. The present study analyzed 8–20 week fetal age human pancreata using scanning and transmission electron microscopy (TEM), TEM immunogold and double or triple immunofluorescence staining. Primary organization of islets and acini occurred during the developmental period examined. Differentiating endocrine and exocrine cells developed from the ductal tubules and subsequently formed isolated small clusters. Extracellular matrix fibers and proteins accumulated around newly differentiated cells during their migration and cluster formation. Glycogen expression was robust in ductal cells of the pancreas from 8–15 weeks of fetal age; however, this became markedly reduced at 20 weeks, with a concomitant increase in acinar cell glycogen content. Insulin secretory granules transformed from being dense and round at 8 weeks to distinct geometric (multilobular, crystalline) structures by 14–20 weeks. Initially many of the differentiating endocrine cells were multihormonal and contained polyhormonal granules; by 20 weeks, monohormonal cells were in the majority. Interestingly, certain secretory granules in the early human fetal pancreatic cells showed positivity for both exocrine (amylase) and endocrine proteins. This combined ultrastructural and immunohistochemical study showed that, during early developmental stages, the human pancreas contains differentiating epithelial cells that associate closely with the extracellular matrix, have dynamic glycogen expression patterns and contain polyhormonal as well as mixed endocrine/exocrine granules. PMID:25425025

  2. Ultrastructural and immunohistochemical analysis of the 8-20 week human fetal pancreas.

    PubMed

    Riopel, Matthew; Li, Jinming; Fellows, George F; Goodyer, Cynthia G; Wang, Rennian

    2014-01-01

    Development of the human pancreas is well-known to involve tightly controlled differentiation of pancreatic precursors to mature cells that express endocrine- or exocrine-specific protein products. However, details of human pancreatic development at the ultrastructural level are limited. The present study analyzed 8-20 week fetal age human pancreata using scanning and transmission electron microscopy (TEM), TEM immunogold and double or triple immunofluorescence staining. Primary organization of islets and acini occurred during the developmental period examined. Differentiating endocrine and exocrine cells developed from the ductal tubules and subsequently formed isolated small clusters. Extracellular matrix fibers and proteins accumulated around newly differentiated cells during their migration and cluster formation. Glycogen expression was robust in ductal cells of the pancreas from 8-15 weeks of fetal age; however, this became markedly reduced at 20 weeks, with a concomitant increase in acinar cell glycogen content. Insulin secretory granules transformed from being dense and round at 8 weeks to distinct geometric (multilobular, crystalline) structures by 14-20 weeks. Initially many of the differentiating endocrine cells were multihormonal and contained polyhormonal granules; by 20 weeks, monohormonal cells were in the majority. Interestingly, certain secretory granules in the early human fetal pancreatic cells showed positivity for both exocrine (amylase) and endocrine proteins. This combined ultrastructural and immunohistochemical study showed that, during early developmental stages, the human pancreas contains differentiating epithelial cells that associate closely with the extracellular matrix, have dynamic glycogen expression patterns and contain polyhormonal as well as mixed endocrine/exocrine granules.

  3. The Human Pancreas Proteome Defined by Transcriptomics and Antibody-Based Profiling

    PubMed Central

    Fagerberg, Linn; Hallström, Björn M.; Schwenk, Jochen M.; Uhlén, Mathias; Korsgren, Olle; Lindskog, Cecilia

    2014-01-01

    The pancreas is composed of both exocrine glands and intermingled endocrine cells to execute its diverse functions, including enzyme production for digestion of nutrients and hormone secretion for regulation of blood glucose levels. To define the molecular constituents with elevated expression in the human pancreas, we employed a genome-wide RNA sequencing analysis of the human transcriptome to identify genes with elevated expression in the human pancreas. This quantitative transcriptomics data was combined with immunohistochemistry-based protein profiling to allow mapping of the corresponding proteins to different compartments and specific cell types within the pancreas down to the single cell level. Analysis of whole pancreas identified 146 genes with elevated expression levels, of which 47 revealed a particular higher expression as compared to the other analyzed tissue types, thus termed pancreas enriched. Extended analysis of in vitro isolated endocrine islets identified an additional set of 42 genes with elevated expression in these specialized cells. Although only 0.7% of all genes showed an elevated expression level in the pancreas, this fraction of transcripts, in most cases encoding secreted proteins, constituted 68% of the total mRNA in pancreas. This demonstrates the extreme specialization of the pancreas for production of secreted proteins. Among the elevated expression profiles, several previously not described proteins were identified, both in endocrine cells (CFC1, FAM159B, RBPJL and RGS9) and exocrine glandular cells (AQP12A, DPEP1, GATM and ERP27). In summary, we provide a global analysis of the pancreas transcriptome and proteome with a comprehensive list of genes and proteins with elevated expression in pancreas. This list represents an important starting point for further studies of the molecular repertoire of pancreatic cells and their relation to disease states or treatment effects. PMID:25546435

  4. The human pancreas proteome defined by transcriptomics and antibody-based profiling.

    PubMed

    Danielsson, Angelika; Pontén, Fredrik; Fagerberg, Linn; Hallström, Björn M; Schwenk, Jochen M; Uhlén, Mathias; Korsgren, Olle; Lindskog, Cecilia

    2014-01-01

    The pancreas is composed of both exocrine glands and intermingled endocrine cells to execute its diverse functions, including enzyme production for digestion of nutrients and hormone secretion for regulation of blood glucose levels. To define the molecular constituents with elevated expression in the human pancreas, we employed a genome-wide RNA sequencing analysis of the human transcriptome to identify genes with elevated expression in the human pancreas. This quantitative transcriptomics data was combined with immunohistochemistry-based protein profiling to allow mapping of the corresponding proteins to different compartments and specific cell types within the pancreas down to the single cell level. Analysis of whole pancreas identified 146 genes with elevated expression levels, of which 47 revealed a particular higher expression as compared to the other analyzed tissue types, thus termed pancreas enriched. Extended analysis of in vitro isolated endocrine islets identified an additional set of 42 genes with elevated expression in these specialized cells. Although only 0.7% of all genes showed an elevated expression level in the pancreas, this fraction of transcripts, in most cases encoding secreted proteins, constituted 68% of the total mRNA in pancreas. This demonstrates the extreme specialization of the pancreas for production of secreted proteins. Among the elevated expression profiles, several previously not described proteins were identified, both in endocrine cells (CFC1, FAM159B, RBPJL and RGS9) and exocrine glandular cells (AQP12A, DPEP1, GATM and ERP27). In summary, we provide a global analysis of the pancreas transcriptome and proteome with a comprehensive list of genes and proteins with elevated expression in pancreas. This list represents an important starting point for further studies of the molecular repertoire of pancreatic cells and their relation to disease states or treatment effects.

  5. On the Psychology of Confessions: Does Innocence Put Innocents at Risk?

    ERIC Educational Resources Information Center

    Kassin, Saul M.

    2005-01-01

    The Central Park jogger case and other recent exonerations highlight the problem of wrongful convictions, 15% to 25% of which have contained confessions in evidence. Recent research suggests that actual innocence does not protect people across a sequence of pivotal decisions: (a) In preinterrogation interviews, investigators commit false-positive…

  6. Ex Vivo Human Pancreatic Slice Preparations Offer a Valuable Model for Studying Pancreatic Exocrine Biology.

    PubMed

    Liang, Tao; Dolai, Subhankar; Xie, Li; Winter, Erin; Orabi, Abrahim I; Karimian, Negar; Cosen-Binker, Laura I; Huang, Ya-Chi; Thorn, Peter; Cattral, Mark; Gaisano, Herbert Y

    2017-02-27

    A genuine understanding of human exocrine pancreas biology and pathobiology has been hampered by a lack of suitable preparations and reliance on rodent models employing dispersed acini preparations. We have developed an organotypic slice preparation of the normal portions of human pancreas obtained from cancer resections. The preparation was assessed for physiologic and pathological responses to the cholinergic agonist carbachol (Cch) and cholecystokinin (CCK-8), including 1) amylase secretion, 2) exocytosis, 3) intracellular Ca2+ responses, 4) cytoplasmic autophagic vacuole formation, and 5) protease activation. Cch and CCK-8 both dose-dependently stimulated secretory responses from human pancreas slices similar to those previously observed in dispersed rodent acini. Confocal microscopy imaging showed that these responses were accounted for by efficient apical exocytosis at physiologic doses of both agonists and by apical blockade and redirection of exocytosis to the basolateral plasma membrane at supramaximal doses. The secretory responses and exocytotic events evoked by CCK-8 were mediated by CCK-A and not CCK-B receptors. Physiologic agonist doses evoked oscillatory Ca2+ increases across the acini. Supraphysiologic doses induced formation of cytoplasmic autophagic vacuoles and activation of proteases (trypsin, chymotrypsin). Maximal atropine pretreatment that completely blocked all the Cch-evoked responses did not affect any of the CCK-8-evoked responses, indicating that rather than acting on the nerves within the pancreas slice, CCK cellular actions directly affected human acinar cells. Human pancreas slices represent excellent preparations to examine pancreatic cell biology and pathobiology and could help screen for potential treatments for human pancreatitis.

  7. Parental Interpretations of "Childhood Innocence": Implications for Early Sexuality Education

    ERIC Educational Resources Information Center

    McGinn, Laura; Stone, Nicole; Ingham, Roger; Bengry-Howell, Andrew

    2016-01-01

    Purpose: Despite general recognition of the benefits of talking openly about sexuality with children, parents encounter and/or create barriers to such communication. One of the key barriers is a desire to protect childhood innocence. The purpose of this paper is to explore parental interpretations of childhood innocence and the influence this has…

  8. Parental Interpretations of "Childhood Innocence": Implications for Early Sexuality Education

    ERIC Educational Resources Information Center

    McGinn, Laura; Stone, Nicole; Ingham, Roger; Bengry-Howell, Andrew

    2016-01-01

    Purpose: Despite general recognition of the benefits of talking openly about sexuality with children, parents encounter and/or create barriers to such communication. One of the key barriers is a desire to protect childhood innocence. The purpose of this paper is to explore parental interpretations of childhood innocence and the influence this has…

  9. Is pancreatic exocrine insufficiency in celiac disease related to structural alterations in pancreatic parenchyma?

    PubMed Central

    Rana, Surinder S.; Dambalkar, Arvind; Chhabra, Puneet; Sharma, Ravi; Nada, Ritambhra; Sharma, Vishal; Rana, Satyavati; Bhasin, Deepak K.

    2016-01-01

    Background Although exocrine pancreatic insufficiency (EPI) has been reported in a number of patients with celiac disease (CD), it is not clear if this is primarily a functional or a structural defect. We studied pancreatic structural abnormalities by endoscopic ultrasound (EUS) in adult CD patients with EPI. Methods Pancreatic exocrine function was prospectively assessed in 36 recently diagnosed CD patients (mean age: 29.8 years) by measuring fecal elastase. Pancreatic structural changes were assessed in CD patients with EPI by EUS and elastography. Exocrine functions were reassessed after 3 months of gluten-free diet. Results Of the 36 CD patients included, 30 (83%) had anemia, 21 (58%) diarrhea, and 7 (19%) hypothyroidism. Ten (28%) patients had EPI with mean elastase levels of 141.6 μg/g of stool, of whom only one had a history of recurrent acute pancreatitis while the rest 9 patients had no history of acute or chronic pancreatitis. Of these 10 patients, 8 (80%) had diarrhea, 8 (80%) anemia, and 2 (20%) hypothyroidism. EUS was done in 8 patients which showed: normal pancreas in 5 (50%), hyperechoic strands in 3 (30%), and hyperechoic foci without shadowing in 2 (20%) patients. None had lobularity or parenchymal calcification. All patients except the patient with recurrent pancreatitis had normal strain ratio. Follow-up fecal elastase was within normal range in 6 of 7 (86%) patients. Conclusion EPI, assessed by fecal elastase levels in adult CD patients, possibly does not relate to structural alterations in the pancreatic parenchyma and may be reversible by following a gluten-free diet. PMID:27366039

  10. Is pancreatic exocrine insufficiency in celiac disease related to structural alterations in pancreatic parenchyma?

    PubMed

    Rana, Surinder S; Dambalkar, Arvind; Chhabra, Puneet; Sharma, Ravi; Nada, Ritambhra; Sharma, Vishal; Rana, Satyavati; Bhasin, Deepak K

    2016-01-01

    Although exocrine pancreatic insufficiency (EPI) has been reported in a number of patients with celiac disease (CD), it is not clear if this is primarily a functional or a structural defect. We studied pancreatic structural abnormalities by endoscopic ultrasound (EUS) in adult CD patients with EPI. Pancreatic exocrine function was prospectively assessed in 36 recently diagnosed CD patients (mean age: 29.8 years) by measuring fecal elastase. Pancreatic structural changes were assessed in CD patients with EPI by EUS and elastography. Exocrine functions were reassessed after 3 months of gluten-free diet. Of the 36 CD patients included, 30 (83%) had anemia, 21 (58%) diarrhea, and 7 (19%) hypothyroidism. Ten (28%) patients had EPI with mean elastase levels of 141.6 μg/g of stool, of whom only one had a history of recurrent acute pancreatitis while the rest 9 patients had no history of acute or chronic pancreatitis. Of these 10 patients, 8 (80%) had diarrhea, 8 (80%) anemia, and 2 (20%) hypothyroidism. EUS was done in 8 patients which showed: normal pancreas in 5 (50%), hyperechoic strands in 3 (30%), and hyperechoic foci without shadowing in 2 (20%) patients. None had lobularity or parenchymal calcification. All patients except the patient with recurrent pancreatitis had normal strain ratio. Follow-up fecal elastase was within normal range in 6 of 7 (86%) patients. EPI, assessed by fecal elastase levels in adult CD patients, possibly does not relate to structural alterations in the pancreatic parenchyma and may be reversible by following a gluten-free diet.

  11. Expression patterns of epiplakin1 in pancreas, pancreatic cancer and regenerating pancreas.

    PubMed

    Yoshida, Tetsu; Shiraki, Nobuaki; Baba, Hideo; Goto, Mizuki; Fujiwara, Sakuhei; Kume, Kazuhiko; Kume, Shoen

    2008-07-01

    Epiplakin1 (Eppk1) is a plakin family gene with its function remains largely unknown, although the plakin genes are known to function in interconnecting cytoskeletal filaments and anchoring them at plasma membrane-associated adhesive junction. Here we analyzed the expression patterns of Eppk1 in the developing and adult pancreas in the mice. In the embryonic pancreas, Eppk1+/Pdx1+ and Eppk1+/Sox9+ pancreatic progenitor cells were observed in early pancreatic epithelium. Since Pdx1 expression overlapped with that of Sox9 at this stage, these multipotent progenitor cells are Eppk1+/Pdx1+/Sox9+ cells. Then Eppk1 expression becomes confined to Ngn3+ or Sox9+ endocrine progenitor cells, and p48+ exocrine progenitor cells, and then restricted to the duct cells and a cells at birth. In the adult pancreas, Eppk1 is expressed in centroacinar cells (CACs) and in duct cells. Eppk1 is observed in pancreatic intraepithelial neoplasia (PanIN), previously identified as pancreatic ductal adenocarcinoma (PDAC) precursor lesions. In addition, the expansion of Eppk1-positive cells occurs in a caerulein-induced acute pancreatitis, an acinar cell regeneration model. Furthermore, in the partial pancreatectomy (Px) regeneration model using mice, Eppk1 is expressed in "ducts in foci", a tubular structure transiently induced. These results suggest that Eppk1 serves as a useful marker for detecting pancreatic progenitor cells in developing and regenerating pancreas.

  12. An Apparent Deficiency of Lymphatic Capillaries in the Islets of Langerhans in the Human Pancreas.

    PubMed

    Korsgren, Erik; Korsgren, Olle

    2016-04-01

    The lymphatic system is crucial for efficient immune surveillance and for the maintenance of a physiological pressure in the interstitial space. Even so, almost no information is available concerning the lymph drainage of the islets of Langerhans in the human pancreas. Immunohistochemical staining allowed us to distinguish lymphatic capillaries from blood capillaries. Almost no lymphatic capillaries were found within the islets in pancreatic biopsy specimens from subjects without diabetes or from subjects with type 1 or type 2 diabetes. Lymphatic capillaries were, however, found at the islet-exocrine interface, frequently located along blood capillaries and other fibrotic structures within or close to the islet capsule. Lymphatic capillaries were regularly found in the exocrine pancreas, with small lymphatic vessels located close to and around acini. Larger collecting lymphatic vessels were located in fibrotic septa between the exocrine lobules and adjacent to the ductal system of the pancreas. In summary, we report a pronounced deficiency of lymphatic capillaries in human islets, a finding with implications for immune surveillance and the regulation of interstitial fluid transport in the endocrine pancreas as well as for the pathophysiology of both type 1 and type 2 diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  13. Functional studies of the parotid and pancreas glands in amyotrophic lateral sclerosis.

    PubMed

    Charchaflie, R J; Bustos Fernandez, L; Perec, C J; Gonzalez, E; Marzi, A

    1974-07-01

    Functional studies of the pancreas and parotid glands are reported in 17 patients with amyotrophic lateral sclerosis (ALS). The exocrine function of the pancreas was studied by measuring amylase concentration after stimulation with the endogenous secretin-pancreozymine test (ESP). Under these conditions, the pancreatic amylase concentration in ALS patients was found to be markedly decreased by about 45% when compared with those of healthy control subjects. Different conclusions in the literature about a possible impairment of the exocrine pancreas in ALS patients induced us to study the function of the parotid gland, which has close structural, functional, and physiopathological relationship with the pancreas. Flow rate and bicarbonate concentration of parotid saliva were measured after indirect stimulation (intraoral citric acid) and direct stimulation (pilocarpine). After indirect stimulation, both parotid flow rate and bicarbonate concentration from ALS patients were found to be decreased by about 66% and 70% respectively, when compared with controls. On the other hand, direct stimulation with pilocarpine in ALS patients elicited normal responses in both flow rate and bicarbonate concentration of saliva. It is concluded that the pancreatic and parotid deficiencies observed in ALS patients do not indicate primary disease of these exocrine glands. This interpretation is further emphasized by the results obtained by a sweat test, plasma osmolarity, and sialographic studies. The possibility that the gland impairments observed might be due to modifications of the neuroendocrine mechanisms regulating their secretory activity is suggested.

  14. Functional studies of the parotid and pancreas glands in amyotrophic lateral sclerosis

    PubMed Central

    Charchaflie, R. J.; Fernandez, L. Bustos; Perec, C. J.; Gonzalez, E.; Marzi, A.

    1974-01-01

    Functional studies of the pancreas and parotid glands are reported in 17 patients with amyotrophic lateral sclerosis (ALS). The exocrine function of the pancreas was studied by measuring amylase concentration after stimulation with the endogenous secretin-pancreozymine test (ESP). Under these conditions, the pancreatic amylase concentration in ALS patients was found to be markedly decreased by about 45% when compared with those of healthy control subjects. Different conclusions in the literature about a possible impairment of the exocrine pancreas in ALS patients induced us to study the function of the parotid gland, which has close structural, functional, and physiopathological relationship with the pancreas. Flow rate and bicarbonate concentration of parotid saliva were measured after indirect stimulation (intraoral citric acid) and direct stimulation (pilocarpine). After indirect stimulation, both parotid flow rate and bicarbonate concentration from ALS patients were found to be decreased by about 66% and 70% respectively, when compared with controls. On the other hand, direct stimulation with pilocarpine in ALS patients elicited normal responses in both flow rate and bicarbonate concentration of saliva. It is concluded that the pancreatic and parotid deficiencies observed in ALS patients do not indicate primary disease of these exocrine glands. This interpretation is further emphasized by the results obtained by a sweat test, plasma osmolarity, and sialographic studies. The possibility that the gland impairments observed might be due to modifications of the neuroendocrine mechanisms regulating their secretory activity is suggested. PMID:4852110

  15. Stereological analyses of the whole human pancreas

    PubMed Central

    Poudel, Ananta; Fowler, Jonas L.; Zielinski, Mark C.; Kilimnik, German; Hara, Manami

    2016-01-01

    The large size of human tissues requires a practical stereological approach to perform a comprehensive analysis of the whole organ. We have developed a method to quantitatively analyze the whole human pancreas, as one of the challenging organs to study, in which endocrine cells form various sizes of islets that are scattered unevenly throughout the exocrine pancreas. Furthermore, the human pancreas possesses intrinsic characteristics of intra-individual variability, i.e. regional differences in endocrine cell/islet distribution, and marked inter-individual heterogeneity regardless of age, sex and disease conditions including obesity and diabetes. The method is built based on large-scale image capture, computer-assisted unbiased image analysis and quantification, and further mathematical analyses, using widely-used software such as Fiji/ImageJ and MATLAB. The present study includes detailed protocols of every procedure as well as all the custom-written computer scripts, which can be modified according to specific experimental plans and specimens of interest. PMID:27658965

  16. Exocrine pancreatic cancer: symptoms at presentation and their relation to tumour site and stage.

    PubMed

    Porta, Miquel; Fabregat, Xavier; Malats, Núria; Guarner, Luisa; Carrato, Alfredo; de Miguel, Ana; Ruiz, Laura; Jariod, Manuel; Costafreda, Sergi; Coll, Susana; Alguacil, Juan; Corominas, Josep M; Solà, Ricard; Salas, Antonio; Real, Francisco X

    2005-06-01

    The need to detect pancreatic cancer at earlier stages is undisputed. We recorded the signs and symptoms of patients presenting with exocrine pancreatic cancer and evaluated their association with clinical characteristics such as tumour site and disease stage. All patients (n = 185) with exocrine pancreatic cancer newly diagnosed at five general hospitals in Eastern Spain were prospectively recruited over 5 years. Symptoms were elicited through personal interviews and signs were recorded by the attending physician on admission. At diagnosis, one third of tumours of the pancreas head were in stage I and another third in stage IV. None of the tumours of the body and tail were in stage I, and over 80% were in stage IV (p < 0.001) . At presentation, the most frequent symptoms were asthenia (86%), anorexia (85%), weight-loss (85%), abdominal pain (79%), and choluria (59%). Cholestatic symptoms were more common in tumours affecting only the pancreatic head (p < 0.001) . There was a clear trend toward more localized tumours with increasing numbers of cholestatic signs (p < 0.001) . Asthenia, anorexia and weight-loss were unrelated to stage. An increased symptom-to-diagnosis interval was associated with more advanced stage (p = 0.048). Proper attention to signs and symptoms, especially cholestasis, may help identify patients with pancreatic cancer at an earlier stage. Results also provide a current picture of the semiology of pancreatic cancer which could be of use in studies on the potential of proteomic tests in the early detection of this neoplasm.

  17. Proteomic Analysis of Disease Stratified Human Pancreas Tissue Indicates Unique Signature of Type 1 Diabetes.

    PubMed

    Burch, Tanya C; Morris, Margaret A; Campbell-Thompson, Martha; Pugliese, Alberto; Nadler, Jerry L; Nyalwidhe, Julius O

    2015-01-01

    Type 1 diabetes (T1D) and type 2 diabetes (T2D) are associated with functional beta cell loss due to ongoing inflammation. Despite shared similarities, T1D is an autoimmune disease with evidence of autoantibody production, as well as a role for exocrine pancreas involvement. Our hypothesis is that differential protein expression occurs in disease stratified pancreas tissues and regulated proteins from endocrine and exocrine tissues are potential markers of disease and potential therapeutic targets. The study objective was to identify novel proteins that distinguish the pancreas from donors with T1D from the pancreas from patients with T2D, or autoantibody positive non-diabetic donors. Detailed quantitative comprehensive proteomic analysis was applied to snap frozen human pancreatic tissue lysates from organ donors without diabetes, with T1D-associated autoantibodies in the absence of diabetes, with T1D, or with T2D. These disease-stratified human pancreas tissues contain exocrine and endocrine tissues (with dysfunctional islets) in the same microenvironment. The expression profiles of several of the proteins were further verified by western blot. We identified protein panels that are significantly and uniquely upregulated in the three disease-stratified pancreas tissues compared to non-disease control tissues. These proteins are involved in inflammation, metabolic regulation, and autoimmunity, all of which are pathways linked to, and likely involved in, T1 and T2 diabetes pathogenesis. Several new proteins were differentially upregulated in prediabetic, T1D, and T2D pancreas. The results identify proteins that could serve as novel prognostic, diagnostic, and therapeutic tools to preserve functional islet mass in Type 1 Diabetes.

  18. Giant serous microcystic pancreas adenoma.

    PubMed

    Dikmen, Kursat; Bostanci, Hasan; Yildirim, Ali Cihat; Sakrak, Omer; Kerem, Mustafa

    2012-10-10

    Serous cystadenomas are rare tumors comprising 1-2% of exocrine pancreas tumors. They are mostly known as benign conditions but malign transformation as serous cystadenocarcinoma is also reported. It is usually seen in females. Non-specific symptoms, such as abdominal pain or symptoms due to mass affect, are usually seen. A 64-year old female patient was investigated for abdominal pain. Physical and laboratory findings were normal. Abdomen ultrasonography confirmed an 11×9.5 cm solid cystic lesion and abdomen computed tomography scan confirmed a 12×11 cm lobulated cystic solid lesion which had central cystic necrotic areas extending from liver hilus inferiorly. Fine needle biopsy confirmed benign cytology and trucut biopsy of the pancreatic mass reported chronic inflamation. Nevertheless, this mass could have malignant contents and transformation potential. A laparatomy was decided due to patient's symptoms and mass effect. Due to vascular invasion of the tumor, Whipple procedure was performed. The pathology report confirmed serous microcystic adenoma. These rare tumors are usually benign but pre-operative malignity criterias are not identified. There are few differential diagnostic tools for excluding malignity. We suggest surgical resection as best treatment approach for selected cases.

  19. Evidence for a causal relationship between early exocrine pancreatic disease and cystic fibrosis-related diabetes: a Mendelian randomization study.

    PubMed

    Soave, David; Miller, Melissa R; Keenan, Katherine; Li, Weili; Gong, Jiafen; Ip, Wan; Accurso, Frank; Sun, Lei; Rommens, Johanna M; Sontag, Marci; Durie, Peter R; Strug, Lisa J

    2014-06-01

    Circulating immunoreactive trypsinogen (IRT), a biomarker of exocrine pancreatic disease in cystic fibrosis (CF), is elevated in most CF newborns. In those with severe CF transmembrane conductance regulator (CFTR) genotypes, IRT declines rapidly in the first years of life, reflecting progressive pancreatic damage. Consistent with this progression, a less elevated newborn IRT measure would reflect more severe pancreatic disease, including compromised islet compartments, and potentially increased risk of CF-related diabetes (CFRD). We show in two independent CF populations that a lower newborn IRT estimate is associated with higher CFRD risk among individuals with severe CFTR genotypes, and we provide evidence to support a causal relationship. Increased loge(IRT) at birth was associated with decreased CFRD risk in Canadian and Colorado samples (hazard ratio 0.30 [95% CI 0.15-0.61] and 0.39 [0.18-0.81], respectively). Using Mendelian randomization with the SLC26A9 rs7512462 genotype as an instrumental variable since it is known to be associated with IRT birth levels in the CF population, we provide evidence to support a causal contribution of exocrine pancreatic status on CFRD risk. Our findings suggest CFRD risk could be predicted in early life and that maintained ductal fluid flow in the exocrine pancreas could delay the onset of CFRD.

  20. Getting a New Pancreas: Facts about Pancreas Transplants

    MedlinePlus

    ... 1, 2003 December 2006 March 2012 Getting A New Pancreas Facts About Pancreas Transplants American Society of ... represent the views of the Society. _________________________________________________________________ Getting a New Pancreas Facts About Pancreas Transplants When you get ...

  1. Innocent until Primed: Mock Jurors' Racially Biased Response to the Presumption of Innocence

    PubMed Central

    Young, Danielle M.; Levinson, Justin D.; Sinnett, Scott

    2014-01-01

    Background Research has shown that crime concepts can activate attentional bias to Black faces. This study investigates the possibility that some legal concepts hold similar implicit racial cues. Presumption of innocence instructions, a core legal principle specifically designed to eliminate bias, may instead serve as an implicit racial cue resulting in attentional bias. Methodology/Principal findings The experiment was conducted in a courtroom with participants seated in the jury box. Participants first watched a video of a federal judge reading jury instructions that contained presumption of innocence instructions, or matched length alternative instructions. Immediately following this video a dot-probe task was administered to assess the priming effect of the jury instructions. Presumption of innocence instructions, but not the alternative instructions, led to significantly faster response times to Black faces when compared with White faces. Conclusions/Significance These findings suggest that the core principle designed to ensure fairness in the legal system actually primes attention for Black faces, indicating that this supposedly fundamental protection could trigger racial stereotypes. PMID:24643050

  2. Studies on zinc-induced pancreatic exocrine insufficiency and its consequences in the chick

    SciTech Connect

    Lue, J.

    1989-01-01

    Experiments were conducted to investigate the nature of zinc (Zn)-induced pancreatic exocrine damage, some of its consequences and its interaction with other nutrients, especially selenium (Se) and vitamin E (VE) in the chick. When fed excess Zn, the chick pancreas accumulated as much as an order of magnitude more Zn than the liver on a unit weight basis. The levels of activities of pancreatic secretory enzymes were significantly reduced by excess dietary Zn and distortion of the acinar pancreas structure, losses of zymogen granules and varying degree of fibrotic infiltration were observed histologically. The reduction of the level of pancreatic secretory enzyme activities was accompanied by a reduction of the quantity of enzyme proteins rather than a modification of enzyme activity. The rate of synthesis of pancreatic amylase, as assessed by the incorporation of {sup 3}H-leucine, was significantly decreased by excess dietary Zn. As consequences of Zn-induced pancreatic damage, the digestibility of dietary starch and tissue VE status were decreased, the latter effect being caused primarily by an impaired utilization of dietary source of the vitamin as determined by the appearance of {sup 3}H-{alpha}-tocopherol in the blood after an oral dose. Excess dietary Zn increased the Se status of the pancreas, but not those of the plasma and the liver. Supranutritional levels of Se and/or VE did not protect the pancreas against Zn-induced damage, nor did Se-deficiency exacerbate this damage. An in vitro inhibitory effect of Zn and some heavy metal ions on {alpha}-amylase activity was discovered and characterized by a non-competitive mechanism. This inhibitory effect could become an important modular of utilization of dietary starch under conditions of Zn toxicosis.

  3. Distinct enhancers of ptf1a mediate specification and expansion of ventral pancreas in zebrafish

    PubMed Central

    Pashos, Evanthia; Park, Joon Tae; Leach, Steven; Fisher, Shannon

    2016-01-01

    Development of the pancreas and cerebellum require Pancreas-specific transcription factor 1a (Ptf1a), which encodes a subunit of the transcription factor complex PTF1. Ptf1a is required in succession for specification of the pancreas, proper allocation of pancreatic progenitors to endocrine and exocrine fates, and the production of digestive enzymes from the exocrine acini. In several neuronal structures, including the cerebellum, hindbrain, retina and spinal cord, Ptf1a is transiently expressed and promotes inhibitory neuron fates at the expense of excitatory fates. Transcription of Ptf1a in mouse is maintained in part by PTF1 acting on an upstream autoregulatory enhancer. However, the transcription factors and enhancers that initially activate Ptf1a expression in the pancreas and in certain structures of the nervous system have not yet been identified. Here we describe a zebrafish autoregulatory element, conserved among teleosts, with activity similar to that described in mouse. In addition, we performed a comprehensive survey of all non-coding sequences in a 67 kilobase interval encompassing zebrafish ptf1a, and identified several neuronal enhancers, and an enhancer active in the ventral pancreas prior to activation of the autoregulatory enhancer. To test the requirement for autoregulatory control during pancreatic development, we restored ptf1a function through BAC transgenesis in ptf1a morphants, either with an intact BAC or one lacking the autoregulatory enhancer. We find that ptf1a autoregulation is required for development of the exocrine pancreas and full rescue of the ptf1a morphant phenotype. Similarly, we demonstrate that a ptf1a locus lacking the early enhancer region is also capable of rescue, but only supports formation of a hypoplastic exocrine pancreas. Through our dissection of the complex regulatory control of ptf1a, we identified separate cis–regulatory elements that underlie different aspects of its expression and function, and further

  4. Compative study of bladder versus enteric drainage in pancreas transplantation.

    PubMed

    Jiménez-Romero, C; Manrique, A; Meneu, J C; Cambra, F; Andrés, A; Morales, J M; González, E; Hernández, E; Morales, E; Praga, M; Gutierrez, E; Moreno, E

    2009-01-01

    There is some controversy concerning the choice of best technique for drainage of exocrine secretions in pancreas transplantation. We compared patients with bladder drainage (BD) versus those with enteric drainage (ED). From March 1995 to September 2008, 118 patients (68 men and 50 women) of overall mean age of 37.8 +/- 7.8 years underwent pancreas transplantation. There were 109 simultaneous pancreas-kidney, and 9 pancreas after kidney procedures. Recipients were divided in a BD (n = 66 patients) and an ED group (n = 52). Donor characteristics were similar in both groups. Thirty-two patients (48.5%) of the BD group versus none in the ED group experienced urinary tract infections (UTI; P < .001), and 16 patients (24.2%) BD versus 15 (29.4%) ED developed intraabdominal infections (P = NS). The overall rate of relaparotomies was 33.9% (n = 40): 34.8% (n = 23) in the BD versus 32.7% (n = 17) in the ED group (P = NS). Thirty patients (25.4%) lost their pancreas grafts: 21 (31.8%) in the BD group versus 9 (17.3%) in the ED group (P = .055). The acute rejection rates were 12.7%; namely, 15.2% in the BD versus 9.8% in the ED (P = NS). Three-year patient and graft survivals were equivalent in both groups: 96.1% and 65.3% in the BD versus 89.0% and 74.0% in the ED group, respectively (P = NS). ED is a good alternative to BD for drainage of pancreatic graft exocrine secretions because both techniques have the same patient and graft survival, but BD is associated with a significantly higher rate of UTI and urologic complications.

  5. Pheromones and exocrine glands in Isoptera.

    PubMed

    Costa-Leonardo, Ana Maria; Haifig, Ives

    2010-01-01

    Termites are eusocial insects that have a peculiar and intriguing system of communication using pheromones. The termite pheromones are composed of a blend of chemical substances and they coordinate different social interactions or activities, including foraging, building, mating, defense, and nestmate recognition. Some of these sociochemicals are volatile, spreading in the air, and others are contact pheromones, which are transmitted by trophallaxis and grooming. Among the termite semiochemicals, the most known are alarm, trail, sex pheromones, and hydrocarbons responsible for the recognition of nestmates. The sources of the pheromones are exocrine glands located all over the termite body. The principal exocrine structures considered pheromone-producing glands in Isoptera are the frontal, mandibular, salivary or labial, sternal, and tergal glands. The frontal gland is the source of alarm pheromone and defensive chemicals, but the mandibular secretions have been little studied and their function is not well established in Isoptera. The secretion of salivary glands involves numerous chemical compounds, some of them without pheromonal function. The worker saliva contains a phagostimulating pheromone and probably a building pheromone, while the salivary reservoir of some soldiers contains defensive chemicals. The sternal gland is the only source of trail-following pheromone, whereas sex pheromones are secreted by two glandular sources, the sternal and tergal glands. To date, the termite semiochemicals have indicated that few molecules are involved in their chemical communication, that is, the same compound may be secreted by different glands, different castes and species, and for different functions, depending on the concentration. In addition to the pheromonal parsimony, recent studies also indicate the occurrence of a synergic effect among the compounds involved in the chemical communication of Isoptera. Copyright © 2010 Elsevier Inc. All rights reserved.

  6. What Is the Pancreas?

    MedlinePlus

    ... Trials Database Supporting Research Raising Awareness Our Blog Patient Education Pancreas News Basics of Pancreatic Cancer FAQs The ... Detection- Goggins Lab Sol Goldman Center Discussion Board Patient Education / Basics of Pancreatic Cancer The Pancreas Parts of ...

  7. Pancreas transplant - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100129.htm Pancreas transplant - series—Normal anatomy To use the sharing ... to slide 6 out of 6 Overview The pancreas resides in the back of the abdomen. It ...

  8. Annular pancreas (image)

    MedlinePlus

    Annular pancreas is an abnormal ring or collar of pancreatic tissue that encircles the duodenum (the part of the ... intestine that connects to stomach). This portion of pancreas can constrict the duodenum and block or impair ...

  9. Polyamine biosynthesis is critical for growth and differentiation of the pancreas

    PubMed Central

    Mastracci, Teresa L.; Robertson, Morgan A.; Mirmira, Raghavendra G.; Anderson, Ryan M.

    2015-01-01

    The pancreas, in most studied vertebrates, is a compound organ with both exocrine and endocrine functions. The exocrine compartment makes and secretes digestive enzymes, while the endocrine compartment, organized into islets of Langerhans, produces hormones that regulate blood glucose. High concentrations of polyamines, which are aliphatic amines, are reported in exocrine and endocrine cells, with insulin-producing β cells showing the highest concentrations. We utilized zebrafish as a model organism, together with pharmacological inhibition or genetic manipulation, to determine how polyamine biosynthesis functions in pancreatic organogenesis. We identified that inhibition of polyamine biosynthesis reduces exocrine pancreas and β cell mass, and that these reductions are at the level of differentiation. Moreover, we demonstrate that inhibition of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis, phenocopies inhibition or knockdown of the enzyme deoxyhypusine synthase (DHS). These data identify that the pancreatic requirement for polyamine biosynthesis is largely mediated through a requirement for spermidine for the downstream posttranslational modification of eIF5A by its enzymatic activator DHS, which in turn impacts mRNA translation. Altogether, we have uncovered a role for polyamine biosynthesis in pancreatic organogenesis and identified that it may be possible to exploit polyamine biosynthesis to manipulate pancreatic cell differentiation. PMID:26299433

  10. Heme acts through the Bach1b/Nrf2a-MafK pathway to regulate exocrine peptidase precursor genes in porphyric zebrafish

    PubMed Central

    Zhang, Shuqing; Xu, Minrui; Huang, Jian; Tang, Lili; Zhang, Yanqing; Wu, Jingyao; Lin, Shuo; Wang, Han

    2014-01-01

    Using a zebrafish model of hepatoerythropoietic porphyria (HEP), we identify a previously unknown mechanism underlying heme-mediated regulation of exocrine zymogens. Zebrafish bach1b, nrf2a and mafK are all expressed in the zebrafish exocrine pancreas. Overexpression of bach1b or knockdown of nrf2a result in the downregulation of the expression of the exocrine zymogens, whereas overexpression of nrf2a or knockdown of bach1b cause their upregulation. In vitro luciferase assays demonstrate that heme activates the zymogens in a dosage-dependent manner and that the zymogen promoter activities require the integral Maf recognition element (MARE) motif. The Bach1b-MafK heterodimer represses the zymogen promoters, whereas the Nrf2a-MafK heterodimer activates them. Furthermore, chromatin immunoprecipitation (ChIP) assays show that MafK binds to the MARE sites in the 5′ regulatory regions of the zymogens. Taken together, these data indicate that heme stimulates the exchange of Bach1b for Nrf2a at MafK-occupied MARE sites and that, particularly in heme-deficient porphyria, the repressive Bach1b-MafK heterodimer dominates, which can be exchanged for the activating Nrf2a-MafK heterodimer upon treatment with hemin. These results provide novel insights into the regulation of exocrine function, as well as the pathogenesis of porphyria, and should be useful for designing new therapies for both types of disease. PMID:24652768

  11. Collision of extensive exocrine and neuroendocrine neoplasms in multiple endocrine neoplasia type 1 revealed by cytogenetic analysis of loss of heterozygosity: a case report.

    PubMed

    Moriyoshi, Koki; Minamiguchi, Sachiko; Miyagawa-Hayashino, Aya; Fujimoto, Masakazu; Kawaguchi, Michiya; Haga, Hironori

    2013-09-01

    The combination of exocrine and neuroendocrine neoplasms is rarely found in the pancreas. These combined lesions vary from a clonal tumor with mixed differentiation to the incidental co-existence of two or more independent tumors, but the differential diagnosis is sometimes difficult. Here we report a case of multiple endocrine neoplasia type 1 (MEN1) with extensive ductal and neuroendocrine neoplastic changes. These two types of tumors admixed markedly in some parts, which made it difficult to determine the pathological diagnosis based on histological findings. Cytogenetic analysis showed that loss of heterozygosity (LOH) of the MEN1 locus exists in neuroendocrine but not in exocrine neoplasms, indicating that independent mechanisms of tumorigenesis may occur in these two types of tumors. This case shows the usefulness of cytogenetic analysis for the diagnosis of combined tumors of the pancreas. Extensive exocrine neoplastic change, including pancreatic intraepithelial neoplasia (PanIN) in virtually all pancreatic ducts and a focus of intraductal papillary mucinous neoplasm (IPMN) with focal invasion, was a distinguishing feature of the present case. The possible association of ductal tumorigenesis and a MEN1 background is discussed.

  12. Pancreas transplantation: review

    PubMed Central

    Meirelles, Roberto Ferreira; Salvalaggio, Paolo; Pacheco-Silva, Alvaro

    2015-01-01

    ABSTRACT Vascularized pancreas transplantation is the only treatment that establishes normal glucose levels and normalizes glycosylated hemoglobin levels in type 1 diabetic patients. The first vascularized pancreas transplant was performed by William Kelly and Richard Lillehei, to treat a type 1 diabetes patient, in December 1966. In Brazil, Edison Teixeira performed the first isolated segmental pancreas transplant in 1968. Until the 1980s, pancreas transplants were restricted to a few centers of the United States and Europe. The introduction of tacrolimus and mycophenolate mofetil in 1994, led to a significant outcome improvement and consequently, an increase in pancreas transplants in several countries. According to the International Pancreas Transplant Registry, until December 31st, 2010, more than 35 thousand pancreas transplants had been performed. The one-year survival of patients and pancreatic grafts exceeds 95 and 83%, respectively. The better survival of pancreatic (86%) and renal (93%) grafts in the first year after transplantation is in the simultaneous pancreas-kidney transplant group of patients. Immunological loss in the first year after transplant for simultaneous pancreas-kidney, pancreas after kidney, and pancreas alone are 1.8, 3.7, and 6%, respectively. Pancreas transplant has 10 to 20% surgical complications requiring laparotomy. Besides enhancing quality of life, pancreatic transplant increases survival of uremic diabetic patient as compared to uremic diabetic patients on dialysis or with kidney transplantation alone. PMID:26154551

  13. Exocrine pancreatic function in children with Alagille syndrome

    PubMed Central

    Gliwicz, Dorota; Jankowska, Irena; Wierzbicka, Aldona; Miśkiewicz-Chotnicka, Anna; Lisowska, Aleksandra; Walkowiak, Jarosław

    2016-01-01

    Alagille syndrome (AGS) is often associated with symptoms of maldigestion, such as steatorrhea, hypotrophy and growth retardation. Exocrine pancreatic insufficiency was proposed as the underlying cause. We aimed to assess the exocrine pancreatic function with the use of different methods in AGS patients. Concentrations of fecal elastase-1 (FE1) and fecal lipase (FL) activities were measured in 33 children with AGS. The C-mixed triglyceride breath test (MTBT) in a subgroup comprising 15 patients. In all patients studied, FE1 concentrations and FL activities were normal. Abnormal MTBT results were documented in 4 (26.7%) patients. The FE1 and FL levels in MTBT-positive and MTBT-negative children did not differ. The results of this research do not confirm the presence of exocrine pancreatic dysfunction in AGS patients. Routine screening for exocrine pancreatic insufficiency of this group of patients is not necessary. PMID:27748459

  14. Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development

    PubMed Central

    Nissim, Sahar; Weeks, Olivia; Talbot, Jared C.; Hedgepeth, John W.; Wucherpfennig, Julia; Schatzman-Bone, Stephanie; Swinburne, Ian; Cortes, Mauricio; Alexa, Kristen; Megason, Sean; North, Trista E.; Amacher, Sharon L.; Goessling, Wolfram

    2016-01-01

    The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development. Zygotic loss of nr5a2 in a targeted genetic null mutant disrupted the development of the exocrine pancreas and liver, while leaving the endocrine pancreas intact. Loss of nr5a2 abrogated exocrine pancreas markers such as trypsin, while pancreas progenitors marked by ptf1a or pdx1 remained unaffected, suggesting a role for Nr5a2 in regulating pancreatic acinar cell differentiation. In the developing liver, Nr5a2 regulates hepatic progenitor outgrowth and differentiation, as nr5a2 mutants exhibited reduced hepatoblast markers hnf4α and prox1 as well as differentiated hepatocyte marker fabp10a. Through the first in vivo use of Nr5a2 chemical antagonist Cpd3, the iterative requirement for Nr5a2 for exocrine pancreas and liver differentiation was temporally elucidated: chemical inhibition of Nr5a2 function during hepatopancreas progenitor specification was sufficient to disrupt exocrine pancreas formation and enhance the size of the embryonic liver, suggesting that Nr5a2 regulates hepatic versus pancreatic progenitor fate choice. Chemical inhibition of Nr5a2 at a later time during pancreas and liver differentiation was sufficient to block the formation of mature acinar cells and hepatocytes. These findings define critical iterative and pleiotropic roles for Nr5a2 at distinct stages of pancreas and liver organogenesis, and provide novel perspectives for interpreting the role of Nr5a2 in disease. PMID:27474396

  15. Iterative use of nuclear receptor Nr5a2 regulates multiple stages of liver and pancreas development.

    PubMed

    Nissim, Sahar; Weeks, Olivia; Talbot, Jared C; Hedgepeth, John W; Wucherpfennig, Julia; Schatzman-Bone, Stephanie; Swinburne, Ian; Cortes, Mauricio; Alexa, Kristen; Megason, Sean; North, Trista E; Amacher, Sharon L; Goessling, Wolfram

    2016-10-01

    The stepwise progression of common endoderm progenitors into differentiated liver and pancreas organs is regulated by a dynamic array of signals that are not well understood. The nuclear receptor subfamily 5, group A, member 2 gene nr5a2, also known as Liver receptor homolog-1 (Lrh-1) is expressed in several tissues including the developing liver and pancreas. Here, we interrogate the role of Nr5a2 at multiple developmental stages using genetic and chemical approaches and uncover novel pleiotropic requirements during zebrafish liver and pancreas development. Zygotic loss of nr5a2 in a targeted genetic null mutant disrupted the development of the exocrine pancreas and liver, while leaving the endocrine pancreas intact. Loss of nr5a2 abrogated exocrine pancreas markers such as trypsin, while pancreas progenitors marked by ptf1a or pdx1 remained unaffected, suggesting a role for Nr5a2 in regulating pancreatic acinar cell differentiation. In the developing liver, Nr5a2 regulates hepatic progenitor outgrowth and differentiation, as nr5a2 mutants exhibited reduced hepatoblast markers hnf4α and prox1 as well as differentiated hepatocyte marker fabp10a. Through the first in vivo use of Nr5a2 chemical antagonist Cpd3, the iterative requirement for Nr5a2 for exocrine pancreas and liver differentiation was temporally elucidated: chemical inhibition of Nr5a2 function during hepatopancreas progenitor specification was sufficient to disrupt exocrine pancreas formation and enhance the size of the embryonic liver, suggesting that Nr5a2 regulates hepatic vs. pancreatic progenitor fate choice. Chemical inhibition of Nr5a2 at a later time during pancreas and liver differentiation was sufficient to block the formation of mature acinar cells and hepatocytes. These findings define critical iterative and pleiotropic roles for Nr5a2 at distinct stages of pancreas and liver organogenesis, and provide novel perspectives for interpreting the role of Nr5a2 in disease. Copyright © 2016

  16. [Pancreatic infringement exocrine and endocrine in cystic fibrosis].

    PubMed

    Kessler, L; Abély, M

    2016-12-01

    The exocrine pancreatic insufficiency affects more than 80% of cystic fibrosis (CF) infants. Pancreatic insufficiency is diagnosed by low levels of fecal elastase. An optimal caloric intake, a pancreatic enzyme treatment are the keys to maintain a good nutritional status. The fat soluble vitamins supplementation will be associated with pancreatic enzymes treatment and will be adapted to plasma levels. Iron and oligo-element deficiency such as zinc is common. The pancreatic enzymes function is not optimal in the proximal bowel: the intraluminal intestinal pH is low because of the absence of bicarbonate release by the pancreas. The use of proton pump inhibitors may improve the functionality of pancreatic enzymes treatment. New therapies such as ivacaftor in patients with a G551D mutation allows a weight gain in particular by restoring intestinal pH similar to controls. Lengthening of the life expectancy of patients with CF is accompanied by the emergence new aspects of the disease, especially diabetes, favored by pancreatic cystic fibrosis resulting in an anatomical destruction of pancreatic islets. Currently, diabetes affects a third of the patients after 20 years, and half after 30 years. Cystic fibrosis-related diabetes is a major factor of morbidity-mortality in all stages of the disease and is characterized by a preclinical phase of glucose intolerance particularly long reaching up to 10 years. Its pathophysiology combines a lack of insulin secretion, an insulin resistance secondary to chronic infection, and a decrease in the production of the GIP and GLP-1. The insulin secretion depending on the channel chlorine (Cystic Fibrosis Transmembrane conductance Regulator [CFTR]) activity at the membrane surface of insulin cell is reduced prior to the occurrence of pancreatic histological lesions. At the stage of diabetes, obtaining a normoglycemia by insulin treatment began very early allows to slow the decline of lung function and nutritional status. Given the silent

  17. Percutaneous cytologic diagnosis of solid pseudopapillary tumors of pancreas in children.

    PubMed

    Tlili, Yemen; Thiesse, Philippe; Lemaistre, Anne I; Dubois, Remi; Faure-Conter, Cecile

    2013-03-01

    Solid pseudopapillary tumors of the pancreas, formerly known as Frantz tumors, are rare exocrine tumors that electively affect young women in their second and third decades of life, and are rarely observed in children. Histologic confirmation is nevertheless desirable before proceeding with treatment of pancreatic lesions, as appropriate treatment can range from conservative to ablative surgery. Here, we report 3 cases of solid pseudopapillary tumors of the pancreas and we postulate that percutaneous cytologic sample analysis (instead of biopsy) may be sufficient to reach an accurate diagnosis and eliminate differential diagnosis.

  18. Ontogeny, postnatal development and ageing of endocrine pancreas in Bubalus bubalis

    PubMed Central

    LUCINI, C.; CASTALDO, L.; LAI, O.; DE VICO, G.

    1998-01-01

    The ontogenesis, postnatal development and ageing of the endocrine pancreas in mammals have not been extensively studied. In order to improve understanding of this organ, we studied the buffalo pancreas during fetal and postnatal development. Glucagon, insulin and somatostatin immunoreactive cells (i.c.) were first seen in 2-mo-old embryos. Pancreatic polypeptide (PP) i.c. were observed during the 3rd month of gestation. The early embryo pancreas was almost totally composed of endocrine tissue. The endocrine portion only slightly increased in mass with animal growth, whereas the exocrine portion noticeably increased in mass during the late fetal and postnatal periods. In adults, therefore, the exocrine portion was more evident than the endocrine portion. Three types of islet were observed in fetal and young buffalos: small, large and PP-islets. The small islets were composed of insulin, glucagon, somatostatin and PP i.c. The large islets were primarily composed of insulin i.c. and a few glucagon, somatostatin and PP i.c. The PP islets were mostly composed of PP i.c. with a few somatostatin, insulin and glucagon i.c. The number of large islets greatly diminished by adulthood. Glucagon, insulin, somatostatin and PP i.c. were also seen scattered in the exocrine parenchyma and along the duct epithelium. In the duct epithelium, these cells were either single or grouped, and they sometimes formed a protrusion projecting towards the connective tissue. These morphological features were primarily observed in fetuses and young buffalos. PMID:9688507

  19. Gastric outlet obstruction secondary to solid-pseudopapillary neoplasm of the pancreas in an eight year old child. Report of a case.

    PubMed

    Bidassek, Rick; Spelter, Herbert; Gödde, Daniel; Zirngibl, Hubert; Ambe, Peter C

    2016-01-20

    Solid pseudopapillary neoplasm is a rare cystic tumor of the exocrine pancreas. Abdominal pain or discomfort is the most common symptom, usually in young females. Herein we report the case of an 8 - year old child presenting with symptoms of gastric outlet obstruction. A solid pseudopapillary neoplasm of the pancreatic caput was diagnosed and surgically removed.

  20. An immunohistochemical study of the endocrine pancreas in raptors.

    PubMed

    Palmieri, C; Shivaprasad, H L

    2014-12-01

    The cytoarchitecture of the endocrine pancreas of 10 raptors (golden eagles, peregrine falcons, Saker falcon, turkey vultures, red-tailed hawk and unspecified falcon) was examined by immunohistochemistry. Three islet types were identified: type A mixed islets composed mainly by glucagon (A)-secreting cells, type B mixed islets with predominantly insulin (B)-secreting cell component and type M mixed islets (type M) consisting of variable number of glucagon-, insulin- and somatostatin (D)-secreting cells. The latter were further characterized into Type I, II or III according to the cell distribution of the three cell types. A and D cells were also randomly scattered within the exocrine pancreas. The results of this study suggest that the classical concept in birds of a segregation of A and B cells in well-defined and distinct islets is not applicable in raptors, reflecting an evolutionary adaptation to different dietary habits and variation in developmental mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Inflammation increases cells expressing ZSCAN4 and progenitor cell markers in the adult pancreas

    PubMed Central

    Azuma, Sakiko; Yokoyama, Yukihiro; Yamamoto, Akiko; Kyokane, Kazuhiro; Niida, Shumpei; Ishiguro, Hiroshi; Ko, Minoru S. H.

    2013-01-01

    We have recently identified the zinc finger and SCAN domain containing 4 (Zscan4), which is transiently expressed and regulates telomere elongation and genome stability in mouse embryonic stem (ES) cells. The aim of this study was to examine the expression of ZSCAN4 in the adult pancreas and elucidate the role of ZSCAN4 in tissue inflammation and subsequent regeneration. The expression of ZSCAN4 and other progenitor or differentiated cell markers in the human pancreas was immunohistochemically examined. Pancreas sections of alcoholic or autoimmune pancreatitis patients before and under maintenance corticosteroid treatment were used in this study. In the adult human pancreas a small number of ZSCAN4-positive (ZSCAN4+) cells are present among cells located in the islets of Langerhans, acini, ducts, and oval-shaped cells. These cells not only express differentiated cell markers for each compartment of the pancreas but also express other tissue stem/progenitor cell markers. Furthermore, the number of ZSCAN4+ cells dramatically increased in patients with chronic pancreatitis, especially in the pancreatic tissues of autoimmune pancreatitis actively regenerating under corticosteroid treatment. Interestingly, a number of ZSCAN4+ cells in the pancreas of autoimmune pancreatitis returned to the basal level after 1 yr of maintenance corticosteroid treatment. In conclusion, coexpression of progenitor cell markers and differentiated cell markers with ZSCAN4 in each compartment of the pancreas may indicate the presence of facultative progenitors for both exocrine and endocrine cells in the adult pancreas. PMID:23599043

  2. [Exocrine pancreatic insufficiency and diabetes mellitus].

    PubMed

    Weitgasser, Raimund; Abrahamian, Heidemarie; Clodi, Martin; Zlamal-Fortunat, Sandra; Hammer, Heinz F

    2016-04-01

    Exocrine pancreatic insufficiency (EPI) in diabetic patients is frequent. Studies based on fecal elastase-1 measurement give prevalence rates of 10‒30 % of severe and 22‒56 % of moderate EPI in type 1 and rates of 5‒46 % in type 2 diabetic patients. Nevertheless, not all patients report typical symptoms like diarrhea, steatorrhea and weight loss. For noninvasive testing the determination of fecal elastase-1 has the highest sensitivity and specificity. This test should be performed at least in all symptomatic patients. As differential diagnosis celiac disease (with a prevalence of about 3-5 % of type 1 diabetic patients), autonomic neuropathy, but also diseases like irritable bowel syndrome and gastrointestinal tumors have to be taken into account. Patients with symptoms and a fecal elastase-1 < 100 µg/g should be treated with pancreatic enzymes in adequate daily doses administered at main meals. Treatment improves symptoms significantly, supply with fat soluble vitamins is normalised, risk for osteoporosis is reduced. However, improvement of glucose metabolism has not been demonstrated consistently. A pancreatogenic diabetes, also termed as type 3c diabetes, has not necessarily to be treated with insulin, often-at least initially-treatment with oral antidiabetic drugs is sufficient.

  3. Conversion of exocrine secretions from bladder to enteric drainage in recipients of whole pancreaticoduodenal transplants.

    PubMed Central

    Stephanian, E; Gruessner, R W; Brayman, K L; Gores, P; Dunn, D L; Najarian, J S; Sutherland, D E

    1992-01-01

    Between September 1984 and August 1991, 265 whole pancreaticoduodenal transplants were done at our institution, with bladder drainage of exocrine secretions through a duodenocystostomy. Seventeen patients subsequently underwent conversion from bladder to enteric drainage at 2 to 64 months after transplant. Eight conversion procedures were done to correct chronic intractable metabolic acidosis due to bicarbonate loss from the allograft: seven to alleviate severe dysuria, presumed secondary to the action of graft enzymes on uroepithelium; one to prevent recurrent allograft pancreatitis, presumed secondary to back pressure from the bladder; and one because of graft duodenectomy for severe cytomegalovirus duodenitis with perforation. None were done to correct technical complications from the initial transplant operation. The conversions were done by dividing the graft duodenocystostomy, then re-establishing drainage through a graft duodenal-recipient jejunal anastomosis. A simple loop of recipient jejunum was used for the duodenojejunostomy in 15 cases, and a Roux limb in two. One of those two cases had a previously created Roux limb that was available for use. The other was in the patient who underwent graft duodenectomy and subsequent mucosa-to-mucosa anastomosis of the pancreatic duct to a newly created Roux limb of jejunum. All patients experienced relief of their symptoms after operation. Two patients had surgical complications (12%), an enterotomy in one case, which was closed operatively, and an enterocutaneous fistula in the other case, which healed spontaneously with bowel rest and parenteral nutrition. The drawback to conversion is loss of urine amylase as a marker for rejection, particularly in recipients of solitary pancreas grafts (n = 5). In recipients of simultaneous pancreas-kidney (SPK) allografts (n = 12), the kidney can still be used to monitor for rejection (two with follow-up < 1 year, 10 with follow-up > 1 year). None of our solitary pancreas

  4. Trauma, innocence and the core complex of dissociation.

    PubMed

    Kalsched, Donald E

    2017-09-01

    Trauma survivors often lament that they have lost their innocence or lost their souls and that something vulnerable and whole about themselves has been 'broken' or annihilated. Yet when the psychotherapeutic relationship begins, and symbolic material from dreams and the transference emerges, discernible patterns become apparent, indicating that a core of innocence and vitality has not been totally lost or annihilated. On the contrary, it has been 'saved' by dissociation and its system of inner objects and their protective and/or persecutory narrative 'scripts' or 'schemas'. The dissociative system splits off a wounded, orphaned 'child' in the psyche and clinging to this 'child' is a penumbra of innocence that apparently must be preserved at all costs. Unfortunately the costs of preservation are high because such encapsulated innocence becomes malignant, and the inner world turns perverse and destructive. Only when the wounded, orphaned, and innocent part of the personality is allowed to suffer experience again - this time with the promise of a new outcome - can true healing of trauma occur. How to facilitate this authentic suffering in the face of powerful resistances thrown up by the 'system', will be the focus of this paper. © 2017, The Society of Analytical Psychology.

  5. Comparative effect of distal and proximal intestinal resection and bypass on the rat exocrine pancreas.

    PubMed

    Carreras, O; Carrillo, J C; Murillo, M L; Delgado, M J

    1990-01-01

    We studied the effects of small-bowel resection and bypass on pancreatic function in rats subjected to a 50% distal resection (DR), a 50% proximal resection (PR), a 50% jejunal bypass (BP) or an intestinal transection (SH) (controls). Duodenal contents were collected after cannulation (under basal conditions). Afterwards, an in vivo duodenal perfusion was made using a glucose/saline solution and perfusate was collected for 1 h. Following this, a cholecystokinin (CCK) solution was injected into the jugular vein (1 U/kg body wt.) and perfusion continued for another 1 h. Basal duodenal volume only increased in rats with a PR, and no significant changes occurred in protein content. In basal conditions, no decreases in amylase, lipase, trypsin, or chymotrypsin activities after DR, PR or BP were detected. When animals were subjected to a perfusion and CCK stimulation, no significant changes occurred in animals with BP; the volume was maintained in rats with PR and DR but a decrease in protein and enzymatic contents was found. We concluded that, in basal conditions, the lack (resections) or exclusion (BP) of 50% of the small bowel does not negatively affect the digestive function. When however, a sustained activity is required, the extirpation of intestinal surface provokes a fall in enzymatic activities and is not modified if only the intestinal transit is suppressed, as occurs in the cases of BP.

  6. Intraoperative electron beam radiation therapy (IOEBRT) for carcinoma of the exocrine pancreas

    SciTech Connect

    Dobelbower, R.R. Jr.; Konski, A.A.; Merrick, H.W. III; Bronn, D.G.; Schifeling, D.; Kamen, C. )

    1991-01-01

    The abdominal cavities of 50 patients were explored in a specially constructed intraoperative radiotherapy operating amphitheater at the Medical College of Ohio. Twenty-six patients were treated with intraoperative and postoperative precision high dose external beam therapy, 12 with intraoperative irradiation but no external beam therapy, and 12 with palliative surgery alone. All but two patients completed the postoperative external beam radiation therapy as initially prescribed. The median survival time for patients treated with palliative surgery alone was 4 months, and that for patients treated with intraoperative radiotherapy without external beam therapy was 3.5 months. Patients undergoing intraoperative irradiation and external beam radiation therapy had a median survival time of 10.5 months. Four patients died within 30 days of surgery and two patients died of gastrointestinal hemorrhage 5 months posttreatment.

  7. ptf1a+, ela3l− cells are developmentally maintained progenitors for exocrine regeneration following extreme loss of acinar cells in zebrafish larvae

    PubMed Central

    Schmitner, Nicole; Kohno, Kenji

    2017-01-01

    ABSTRACT The exocrine pancreas displays a significant capacity for regeneration and renewal. In humans and mammalian model systems, the partial loss of exocrine tissue, such as after acute pancreatitis or partial pancreatectomy induces rapid recovery via expansion of surviving acinar cells. In mouse it was further found that an almost complete removal of acinar cells initiates regeneration from a currently not well-defined progenitor pool. Here, we used the zebrafish as an alternative model to study cellular mechanisms of exocrine regeneration following an almost complete removal of acinar cells. We introduced and validated two novel transgenic approaches for genetically encoded conditional cell ablation in the zebrafish, either by caspase-8-induced apoptosis or by rendering cells sensitive to diphtheria toxin. By using the ela3l promoter for exocrine-specific expression, we show that both approaches allowed cell-type-specific removal of >95% of acinar tissue in larval and adult zebrafish without causing any signs of unspecific side effects. We find that zebrafish larvae are able to recover from a virtually complete acinar tissue ablation within 2 weeks. Using short-term lineage-tracing experiments and EdU incorporation assays, we exclude duct-associated Notch-responsive cells as the source of regeneration. Rather, a rare population of slowly dividing ela3l-negative cells expressing ptf1a and CPA was identified as the origin of the newly forming exocrine cells. Cells are actively maintained, as revealed by a constant number of these cells at different larval stages and after repeated cell ablation. These cells establish ela3l expression about 4-6 days after ablation without signs of increased proliferation in between. With onset of ela3l expression, cells initiate rapid proliferation, leading to fast expansion of the ela3l-positive population. Finally, we show that this proliferation is blocked by overexpression of the Wnt-signaling antagonist dkk1b. In

  8. Retinol Dehydrogenase-10 Regulates Pancreas Organogenesis and Endocrine Cell Differentiation via Paracrine Retinoic Acid Signaling.

    PubMed

    Arregi, Igor; Climent, Maria; Iliev, Dobromir; Strasser, Jürgen; Gouignard, Nadège; Johansson, Jenny K; Singh, Tania; Mazur, Magdalena; Semb, Henrik; Artner, Isabella; Minichiello, Liliana; Pera, Edgar M

    2016-12-01

    Vitamin A-derived retinoic acid (RA) signals are critical for the development of several organs, including the pancreas. However, the tissue-specific control of RA synthesis in organ and cell lineage development has only poorly been addressed in vivo. Here, we show that retinol dehydrogenase-10 (Rdh10), a key enzyme in embryonic RA production, has important functions in pancreas organogenesis and endocrine cell differentiation. Rdh10 was expressed in the developing pancreas epithelium and surrounding mesenchyme. Rdh10 null mutant mouse embryos exhibited dorsal pancreas agenesis and a hypoplastic ventral pancreas with retarded tubulogenesis and branching. Conditional disruption of Rdh10 from the endoderm caused increased mortality, reduced body weight, and lowered blood glucose levels after birth. Endodermal Rdh10 deficiency led to a smaller dorsal pancreas with a reduced density of early glucagon(+) and insulin(+) cells. During the secondary transition, the reduction of Neurogenin3(+) endocrine progenitors in the mutant dorsal pancreas accounted for fewer α- and β-cells. Changes in the expression of α- and β-cell-specific transcription factors indicated that Rdh10 might also participate in the terminal differentiation of endocrine cells. Together, our results highlight the importance of both mesenchymal and epithelial Rdh10 for pancreogenesis and the first wave of endocrine cell differentiation. We further propose a model in which the Rdh10-expressing exocrine tissue acts as an essential source of RA signals in the second wave of endocrine cell differentiation.

  9. Preschoolers' Understanding of Lies and Innocent and Negligent Mistakes.

    ERIC Educational Resources Information Center

    Siegal, Michael; Peterson, Candida C.

    1998-01-01

    Examined preschoolers' ability to distinguish innocent and negligent mistakes from lies. Found that, when asked to identify a mistake or lie about a food's contact with contaminants and identify a bystander's reaction, children distinguished mistakes from lies; they could also discriminate between lies and both negligent mistakes that generate…

  10. Visualizing the Politics of Innocence in the Age of AIDS

    ERIC Educational Resources Information Center

    Mitchell, Claudia; Walsh, Shannon; Larkin, June

    2004-01-01

    We are concerned with the ways in which social constructions of age can contribute to reducing or exacerbating the vulnerability of young people, and for this reason we refer to the issue as one of "the politics of innocence". The focus of this paper is on gender, youth and HIV prevention/AIDS awareness in the context of South Africa and…

  11. Preschoolers' Understanding of Lies and Innocent and Negligent Mistakes.

    ERIC Educational Resources Information Center

    Siegal, Michael; Peterson, Candida C.

    1998-01-01

    Examined preschoolers' ability to distinguish innocent and negligent mistakes from lies. Found that, when asked to identify a mistake or lie about a food's contact with contaminants and identify a bystander's reaction, children distinguished mistakes from lies; they could also discriminate between lies and both negligent mistakes that generate…

  12. The Ontogeny of the Endocrine Pancreas in the Fetal/Newborn Baboon

    PubMed Central

    Quinn, Amy R.; Blanco, Cynthia L.; Perego, Carla; Finzi, Giovanna; La Rosa, Stefano; Capella, Carlo; Guardado-Mendoza, Rodolfo; Casiraghi, Francesca; Gastaldelli, Amalia; Johnson, Marney; Dick, Edward J.; Folli, Franco

    2013-01-01

    Background Erratic regulation of glucose metabolism including hyperglycemia is a common condition of premature infants and is associated with increased morbidity and mortality. Objective To examine histological and ultra-structural differences in the endocrine pancreas in fetal (throughout gestation) and neonatal baboons. Methods Twelve fetal baboons were delivered at 125 days (d) gestational age (GA), 140dGA, or 175dGA. Eight animals were delivered at term (185dGA); half were fed for 5d. Seventy-three non-diabetic adult baboons were used for comparison. Pancreatic tissue was studied utilizing light microscopy, confocal imaging and electron microscopy. Results The fetal and neonatal endocrine pancreas islet architecture became more organized as GA advanced. The percent areas of α-β-δ-cell type were similar within each fetal and newborn GA (NS), but were higher than the adults (P<0.05) regardless of GA. The ratio of β-cells within the islet (whole and core) increased with gestation (P<0.01). Neonatal baboons who survived for 5 days (feeding), had a 2.5-fold increase in pancreas weight compared to their counterparts euthanized at birth (P=0.01). Endocrine cells were found amongst exocrine ductal and acinar cells in 125,140 and 175dGA fetuses. Subpopulation of cells that co-expressed trypsin and glucagon/insulin show the presence of cells with mixed endo-exocrine lineage in fetuses. Conclusions The fetal endocrine pancreas has no prevalence of a of α-β-δ-cell type with larger endocrine cell percent areas than adults. Cells with mixed endocrine/exocrine phenotype occur during fetal development. Developmental differences may play a role in glucose homeostasis during the neonatal period and may have long term implications. PMID:22723715

  13. Endocrine and exocrine function of the bovine testis. Chapter 2

    USDA-ARS?s Scientific Manuscript database

    This chapter is devoted to the endocrine and exocrine function of the normal bovine male testes. The discussion begins with a historical review of the literature dating back to Aristotle’s (300 BC) initial description of the anatomy of the mammalian testes. The first microscopic examination of the t...

  14. EXOCRINE PANCREATIC CARCINOGENESIS IN THE GUPPY POECILIA RETICULATA

    EPA Science Inventory

    Exocrine pancreatic neoplasms developed in the guppy Poecilia reticulata following exposure to the direct acting carcinogen, methylazoxymethanol acetate (MAM-Ac). Fish 6- to 10-days old were exposed to nominal, nontoxic concentrations of 4 and 10 mg MAM-Ac 1-1 for 2 h and then tr...

  15. EXOCRINE PANCREATIC CARCINOGENESIS IN THE GUPPY (POECILIA RETICULATA).

    EPA Science Inventory

    Exocrine pancreatic neoplasms developed in the guppy (Poecilia reticulata) following exposure to the direct acting carcinogen, methylazoxymethanol acetate (MAM-Ac). Fish 6- to 10-days old were exposed to nominal, nontoxic concentrations of 4 and 10 mg MAM-Ac/L for 2 hr and then t...

  16. EXOCRINE PANCREATIC CARCINOGENESIS IN THE GUPPY POECILIA RETICULATA

    EPA Science Inventory

    Exocrine pancreatic neoplasms developed in the guppy Poecilia reticulata following exposure to the direct acting carcinogen, methylazoxymethanol acetate (MAM-Ac). Fish 6- to 10-days old were exposed to nominal, nontoxic concentrations of 4 and 10 mg MAM-Ac 1-1 for 2 h and then tr...

  17. EXOCRINE PANCREATIC CARCINOGENESIS IN THE GUPPY (POECILIA RETICULATA).

    EPA Science Inventory

    Exocrine pancreatic neoplasms developed in the guppy (Poecilia reticulata) following exposure to the direct acting carcinogen, methylazoxymethanol acetate (MAM-Ac). Fish 6- to 10-days old were exposed to nominal, nontoxic concentrations of 4 and 10 mg MAM-Ac/L for 2 hr and then t...

  18. Assessment of pancreas cells

    NASA Technical Reports Server (NTRS)

    Vanoss, C. J.

    1978-01-01

    Pancreatic islets were obtained from guinea pig pancreas by the collagenase method and kept alive in tissue culture prior to further studies. Pancreas cell morphology was studied by standard histochemical techniques using light microscopy. Preparative vertical electrophoresis-levitation of dispersed fetal guinea pig pancreas cells was conducted in phosphate buffer containing a heavy water (D20) gradient which does not cause clumping of cells or alter the osmolarity of the buffers. The faster migrating fractions tended to be enriched in beta-cell content. Alpha and delta cells were found to some degree in most fractions. A histogram showing the cell count distribution is included.

  19. Tissue-specific deletion of c-Jun in the pancreas has limited effects on pancreas formation

    SciTech Connect

    Yamamoto, Kaoru; Miyatsuka, Takeshi; Tanaka, Ayako; Toyoda, Shuichi; Kato, Ken; Shiraiwa, Toshihiko; Fujitani, Yoshio; Yamasaki, Yoshimitsu; Hori, Masatsugu; Matsuhisa, Munehide; Matsuoka, Taka-aki; Kaneto, Hideaki

    2007-11-30

    It is well known that activating protein-1 (AP-1) is involved in a variety of cellular functions such as proliferation, differentiation, apoptosis, and oncogenesis. AP-1 is a dimer complex consisting of different subunits, and c-Jun is known to be one of its major components. In addition, it has been shown that mice lacking c-Jun are embryonic lethal and that c-Jun is essential for liver and heart development. However, the role of c-Jun in the pancreas is not well known. The aim of this study was to examine the possible role of c-Jun in the pancreas. First, c-Jun was strongly expressed in pancreatic duct-like structures at an embryonic stage, while a lower level of expression was observed in some part of the adult pancreas, implying that c-Jun might play a role during pancreas development. Second, to address this point, we generated pancreas-specific c-Jun knock-out mice (Ptf1a-Cre; c-Jun{sup flox/flox} mice) by crossing Ptf1a-Cre knock-in mice with c-Jun floxed mice. Ptf1a is a pancreatic transcription factor and its expression is confined to pancreatic stem/progenitor cells, which give rise to all three types of pancreatic tissue: endocrine, exocrine, and duct. Contrary to our expectation, however, there was no morphological difference in the pancreas between Ptf1a-Cre; c-Jun{sup flox/flox} and control mice. In addition, there was no difference in body weight, pancreas weight, and the expression of various pancreas-related factors (insulin, glucagon, cytokeratin, and amylase) between the two groups. Furthermore, there was no difference in glucose tolerance between Ptf1a-Cre; c-Jun{sup flox/flox} and control mice. Taken together, although we cannot exclude the possibility that c-Jun ablation is compensated by some unknown factors, c-Jun appears to be dispensable for pancreas development at least after ptf1a gene promoter is activated.

  20. Calcium and magnesium in exocrine secretion--an X-ray microanalytical study

    SciTech Connect

    Roomans, G.M.; Barnard, T.

    1982-01-01

    Calcium and magnesium distribution in mammalian exocrine glands under resting, stimulated and pathological conditions was investigated by X-ray microanalysis of thick and ultrathin cryosections. Ultrathin sections were cut from tissue frozen in the presence of a polymer cryoprotectant, dextran. The effect of this treatment on isolated rabbit pancreas. Dextran caused a disturbance in water and ion transport, partly due to an osmotic effect and the impermeability of the pancreatic epithelium to dextran; this does, however, not necessarily invalidate intracellular measurements on frozen-dried sections. Cholinergic stimulation of the rat pancreas caused a change of Ca distribution from the basal to the apical part of the cell; this may be a component of the secretory Ca flux. Kinetic considerations make a significant Ca movement via the ER-Golgi endomembrane space less likely. The mitochondrial Ca concentration is low, and not significantly changed by cholinergic stimulation. X-ray microanalysis was carried out on submandibular glands of rats after chronic treatment with reserpin and/or isoproterenol (an animal model for cystic fibrosis, CF). The acinar cells had elevated Mg and Ca and lowered K concentrations. Analysis of ultrathin cryosections showed high levels of Ca and Mg in secretory granules, mucus globules and the ER. Ca and Mg in the ER may be transported intracellularly with secretory proteins to secretion granules or mucus globules. The decrease in cell K may be due to efflux of K caused by elevated cytoplasmic Ca levels. A similar decrease in cell K was caused by incubation of rat salivary glands with diluted serum from CF patients, a treatment which has been reported to mimic the effect of a rise in cytoplasmic Ca.

  1. Relationships between the autonomic nervous system and the pancreas including regulation of regeneration and apoptosis: recent developments.

    PubMed

    Kiba, Takayoshi

    2004-08-01

    Substantial new information has accumulated on the mechanisms of secretion, the development, and regulation of the gene expression, and the role of growth factors in the differentiation, growth, and regeneration of the pancreas. Many genes that are required for pancreas formation are active after birth and participate in endocrine and exocrine cell functions. Although the factors that normally regulate the proliferation of the pancreas largely remain elusive, several factors to influence the growth have been identified. It was also reported that the pancreas was sensitive to a number of apoptotic stimuli. The autonomic nervous system influences many of the functions of the body, including the pancreas. In fact, the parasympathetic nervous system and the sympathetic nervous system have opposing effects on insulin secretion from islet beta cells; feeding-induced parasympathetic neural activity to the pancreas stimulates insulin secretion, whereas stress-induced sympathetic neural activity to the pancreas inhibits insulin secretion. Moreover, it has been reported that the autonomic nervous system is one of the important factors that regulate pancreatic regeneration and stimulate the carcinogenesis. The present review focuses on the relationships between the autonomic nervous system and the pancreas, and furthermore, presents evidence of the autonomic nervous system-related pancreatic regeneration and carcinogenesis.

  2. X-ray microanalysis of exocrine glands in animal models for cystic fibrosis

    SciTech Connect

    Mueller, R.M.R.; Roomans, G.M.

    1985-01-01

    Elemental distribution and ultrastructure of the submandibular gland, the parotid gland and the pancreas were investigated in three suggested animal models of the disease cystic fibrosis: the chronically reserpinized rat, the chronically isoproterenol-treated rat, and the chronically pilocarpine-treated rat. To elucidate the cellular mechanism underlying the effects of these treatments, chronic effects of specific alpha - and beta -adrenergic agonists, as well as acute effects of reserpine and various agonists were also investigated. Reserpine, isoproterenol, and pilocarpine cause an increase in the calcium concentration in submandibular gland acinar cells, due to an increased calcium content of the intracellular mucus. In the parotid gland, reserpine and isoproterenol cause a decrease of the calcium concentration in acinar cells, due to a lower calcium content of the zymogen granules. In the submandibular gland, a decreased cellular Na concentration was noted after chronic treatment with isoproterenol or pilocarpine, and after a single dose of reserpine or isoproterenol. Ultrastructural changes in the exocrine glands investigated included excessive accumulation of intracellular secretory material and formation of abnormal uncondensed secretion granules. A common pattern in the animal models appears to be (1) inhibition of secretion resulting in intracellular accumulation of secretory material, (2) synthesis of secretory macromolecules with altered cation-binding properties.

  3. [Mucinous cystadenocarcinoma of pancreas].

    PubMed

    Davies, Nestor R; Kasparian, Andres C; Viotto, Lucas E; Moreno, Walter A; Gramática, Luis

    2009-01-01

    Mucinous cystadenocarcinoma of the pancreas represents around 6-36% of mucinous cystic neoplasm. The lesions are usually found in the body and tail of the pancreas and are generally solitary with a size range of 6-36 cm. We present a clinical case of a 63 years old patient with abdominal pain and weight loss. We used radiographic imaging studies. It was treated with surgery by distal pancreatectomy with splenectomy and transverse colectomy. Patient was not post operative complications.

  4. Partial annular pancreas

    PubMed Central

    Jindal, Gunjan; Mittal, Amit; Singal, Rikki; Singal, Samita

    2016-01-01

    Annular pancreas is a developmental anomaly that can be associated with other conditions such as Down syndrome, duodenal atresia, and Hirschsprung disease. A band of pancreatic tissue, in continuity with the pancreatic head, completely or incompletely encircles the descending duodenum, sometimes assuming a “crocodile jaw” configuration. We present the case of an adult who presented with epigastric pain and vomiting and was found to have annular pancreas. PMID:27695176

  5. Pancreas and cyst segmentation

    NASA Astrophysics Data System (ADS)

    Dmitriev, Konstantin; Gutenko, Ievgeniia; Nadeem, Saad; Kaufman, Arie

    2016-03-01

    Accurate segmentation of abdominal organs from medical images is an essential part of surgical planning and computer-aided disease diagnosis. Many existing algorithms are specialized for the segmentation of healthy organs. Cystic pancreas segmentation is especially challenging due to its low contrast boundaries, variability in shape, location and the stage of the pancreatic cancer. We present a semi-automatic segmentation algorithm for pancreata with cysts. In contrast to existing automatic segmentation approaches for healthy pancreas segmentation which are amenable to atlas/statistical shape approaches, a pancreas with cysts can have even higher variability with respect to the shape of the pancreas due to the size and shape of the cyst(s). Hence, fine results are better attained with semi-automatic steerable approaches. We use a novel combination of random walker and region growing approaches to delineate the boundaries of the pancreas and cysts with respective best Dice coefficients of 85.1% and 86.7%, and respective best volumetric overlap errors of 26.0% and 23.5%. Results show that the proposed algorithm for pancreas and pancreatic cyst segmentation is accurate and stable.

  6. The Endocrine Pancreas: insights into development, differentiation and diabetes

    PubMed Central

    2012-01-01

    In the developing embryo, appropriate patterning of the endoderm fated to become pancreas requires the spatial and temporal coordination of soluble factors secreted by the surrounding tissues. Once pancreatic progenitor cells are specified in the developing gut tube epithelium, epithelial-mesenchymal interactions, as well as a cascade of transcription factors, subsequently delineate three distinct lineages, including endocrine, exocrine and ductal cells. Simultaneous morphological changes, including branching, vascularization, and proximal organ development, also influence the process of specification and differentiation. Decades of research using mouse genetics have uncovered many of the key factors involved in pancreatic cell fate decisions. When pancreas development or islet cell functions go awry, due to mutation in genes important for proper organogenesis and development, the result can lead to a common pancreatic affliction, diabetes mellitus. Current treatments for diabetes are adequate but not curative. Therefore researchers are utilizing the current understanding of normal embryonic pancreas development in vivo, to direct embryonic stem cells toward a pancreatic fate with the goal of transplanting these in vitro generated “islets” into patients. Mimicking development in vitro has proven difficult; however, significant progress has been made and the current differentiation protocols are becoming more efficient. The continued partnership between developmental biologists and stem cell researchers will guarantee that the in vitro generation of insulin-producing beta cells is a possible therapeutic option for the treatment of diabetes. PMID:22905335

  7. Regeneration of the Pancreas in Adult Zebrafish

    PubMed Central

    Moss, Jennifer B.; Koustubhan, Punita; Greenman, Melanie; Parsons, Michael J.; Walter, Ingrid; Moss, Larry G.

    2009-01-01

    OBJECTIVE Regenerating organs in diverse biological systems have provided clues to processes that can be harnessed to repair damaged tissue. Adult mammalian β-cells have a limited capacity to regenerate, resulting in diabetes and lifelong reliance on insulin. Zebrafish have been used as a model for the regeneration of many organs. We demonstrate the regeneration of adult zebrafish pancreatic β-cells. This nonmammalian model can be used to define pathways for islet-cell regeneration in humans. RESEARCH DESIGN AND METHODS Adult transgenic zebrafish were injected with a single high dose of streptozotocin or metronidazole and anesthetized at 3, 7, or 14 days or pancreatectomized. Blood glucose measurements were determined and gut sections were analyzed using specific endocrine, exocrine, and duct cell markers as well as markers for dividing cells. RESULTS Zebrafish recovered rapidly without the need for insulin injections, and normoglycemia was attained within 2 weeks. Although few proliferating cells were present in vehicles, ablation caused islet destruction and a striking increase of proliferating cells, some of which were Pdx1 positive. Dividing cells were primarily associated with affected islets and ducts but, with the exception of surgical partial pancreatectomy, were not extensively β-cells. CONCLUSIONS The ability of the zebrafish to regenerate a functional pancreas using chemical, genetic, and surgical approaches enabled us to identify patterns of cell proliferation in islets and ducts. Further study of the origin and contribution of proliferating cells in reestablishing islet function could provide strategies for treating human diseases. PMID:19491207

  8. Transepithelial bicarbonate secretion: lessons from the pancreas.

    PubMed

    Park, Hyun Woo; Lee, Min Goo

    2012-10-01

    Many cystic fibrosis transmembrane conductance regulator (CFTR)-expressing epithelia secrete bicarbonate (HCO(3)(-))-containing fluids. Recent evidence suggests that defects in epithelial bicarbonate secretion are directly involved in the pathogenesis of cystic fibrosis, in particular by building up hyperviscous mucus in the ductal structures of the lung and pancreas. Pancreatic juice is one of the representative fluids that contain a very high concentration of bicarbonate among bodily fluids that are secreted from CFTR-expressing epithelia. We introduce up-to-date knowledge on the basic principles of transepithelial bicarbonate transport by showing the mechanisms involved in pancreatic bicarbonate secretion. The model of pancreatic bicarbonate secretion described herein may also apply to other exocrine epithelia. As a central regulator of bicarbonate transport at the apical membrane, CFTR plays an essential role in both direct and indirect bicarbonate secretion. The major role of CFTR in bicarbonate secretion would be variable depending on the tissue and cell type. For example, in epithelial cells that produce a low concentration of bicarbonate-containing fluid (up to 80 mm), either CFTR-dependent Cl(-)/HCO(3)(-) exchange or CFTR anion channel with low bicarbonate permeability would be sufficient to generate such fluid. However, in cells that secrete high-bicarbonate-containing fluids, a highly selective CFTR bicarbonate channel activity is required. Therefore, understanding the molecular mechanism of transepithelial bicarbonate transport and the role of CFTR in each specific epithelium will provide therapeutic strategies to recover from epithelial defects induced by hyposecretion of bicarbonate in cystic fibrosis.

  9. Epidemiology of pancreas cancer in Los Angeles

    SciTech Connect

    Mack, T.M.; Paganini-Hill, A.

    1981-03-15

    The characteristics of the 3614 Los Angeles County residents in whom cancer of the exocrine pancreas was diagnosed during the period 1972-1977 were compared with those of all county residents and patients in whom any cancer was diagnosed during the same period. Seventy-nine percent of the diagnoses had been pathologically verified. This disease still preferentially afflicts the old, the black, and men, although the differences in risk with factors other than age are modest. The disease is not evenly distributed by social class, or over time, although it is not clear that the observed differences reflect etiology. The distributions with respect to important categories of occupation and industry, religion, marital status, geography of residence, and birthplace were rather uniform. Although there is no obvious explanation for any of several unexpected minor inequities in the pattern of incidence, there is no compelling evidence to support any specific environmental cause. There is substantial evidence which is inconsistent with those environmental hypotheses that have been proposed previously.

  10. Onset of cell-specific gene expression in the developing mouse pancreas.

    PubMed Central

    Gittes, G K; Rutter, W J

    1992-01-01

    A central question in developmental biology has been the initiation of cell-specific gene expression and its temporal relationship to morphogenesis. We have coupled embryo microdissection with the exquisite sensitivity of the polymerase chain reaction to define the onset of cell-specific gene expression during pancreatic organogenesis. Using the precise assignment of gestational age by the number of somites in each embryo, we determined the onset of transcription of major genes of the endocrine and exocrine pancreas during mouse development to within 2-3 hr. Somatostatin mRNA was detected at the 10-somite stage throughout the foregut, consistent with the presence of somatostatin-producing cells throughout the adult gut. Mature mRNA for insulin and glucagon first appears surprisingly early, at the 20-somite stage in the wall of the embryonic foregut and is restricted to only the area of the duodenum from which the pancreas will arise 10-12 hr later. In contrast, exocrine gene transcription begins 24 hr after formation of the pancreatic diverticulum. Thus cell-specific gene expression in the endocrine pancreas begins in a "pre-morphogenetic phase." This early expression of insulin and glucagon could reflect the initiation of an endocrine cell lineage. Images PMID:1371010

  11. Histologic effects of University of Wisconsin two-layer method preservation of rat pancreas.

    PubMed

    Gioviale, M C; Damiano, G; Puleio, R; Bellavia, M; Cassata, G; Palumbo, V D; Spinelli, G; Altomare, R; Barone, R; Cacciabaudo, F; Buscemi, G; Lo Monte, A I

    2013-06-01

    Marginal donors represent a poorly utilized source of organs for transplantation despite their availability. The key is to reduce the ischemic damage in the effort to improve organ quality. This study investigated the histologic effects after in situ perfusion of preservation with a two-layer method compared with the classic University of Wisconsin preservation in term of tissue integrity and number of viable exocrine cells in the rat pancreas both after exsanguination and at 8 weeks of cryopreservation. Pancreata harvested from 60 rats were collected using 3 methods: two-layer method following University of Wisconsin perfusion; exsanguination; and classic University of Wisconsin perfusion/storage. In addition to histologic analysis of collected pancreata, we analyzed the number of CK19(+) cells and their viability using chi-square tests with values P < .05 considered to be significant. Rat pancreas histology showed as University of Wisconsin in situ perfusion and preservation by the two-layer method to be more effective to maintain the morphologic integrity of both exocrine and endocrine tissues. There were a larger number of CK19(+) cells with good viability. Moreover, the effects of oxygenation were visible in pancreas biopsies preserved after exsanguination. In situ University of Wisconsin perfusion and preservation for 240 minutes with the two-layer method yielded greater numbers and viability of CK19(+) cells even after 8 weeks of cryopreservation.

  12. Possible type 1 diabetes risk prediction: Using ultrasound imaging to assess pancreas inflammation in the inducible autoimmune diabetes BBDR model.

    PubMed

    Roberts, Frederick R; Hupple, Clinton; Norowski, Elaine; Walsh, Nicole C; Przewozniak, Natalia; Aryee, Ken-Edwin; Van Dessel, Filia M; Jurczyk, Agata; Harlan, David M; Greiner, Dale L; Bortell, Rita; Yang, Chaoxing

    2017-01-01

    Studies of human cadaveric pancreas specimens indicate that pancreas inflammation plays an important role in type 1 diabetes pathogenesis. Due to the inaccessibility of pancreas in living patients, imaging technology to visualize pancreas inflammation is much in need. In this study, we investigated the feasibility of utilizing ultrasound imaging to assess pancreas inflammation longitudinally in living rats during the progression leading to type 1 diabetes onset. The virus-inducible BBDR type 1 diabetes rat model was used to systematically investigate pancreas changes that occur prior to and during development of autoimmunity. The nearly 100% diabetes incidence upon virus induction and the highly consistent time course of this rat model make longitudinal imaging examination possible. A combination of histology, immunoblotting, flow cytometry, and ultrasound imaging technology was used to identify stage-specific pancreas changes. Our histology data indicated that exocrine pancreas tissue of the diabetes-induced rats underwent dramatic changes, including blood vessel dilation and increased CD8+ cell infiltration, at a very early stage of disease initiation. Ultrasound imaging data revealed significant acute and persistent pancreas inflammation in the diabetes-induced rats. The pancreas micro-vasculature was significantly dilated one day after diabetes induction, and large blood vessel (superior mesenteric artery in this study) dilation and inflammation occurred several days later, but still prior to any observable autoimmune cell infiltration of the pancreatic islets. Our data demonstrate that ultrasound imaging technology can detect pancreas inflammation in living rats during the development of type 1 diabetes. Due to ultrasound's established use as a non-invasive diagnostic tool, it may prove useful in a clinical setting for type 1 diabetes risk prediction prior to autoimmunity and to assess the effectiveness of potential therapeutics.

  13. Portal Annular Pancreas

    PubMed Central

    Harnoss, Jonathan M.; Harnoss, Julian C.; Diener, Markus K.; Contin, Pietro; Ulrich, Alexis B.; Büchler, Markus W.; Schmitz-Winnenthal, Friedrich H.

    2014-01-01

    Abstract Portal annular pancreas (PAP) is an asymptomatic congenital pancreas anomaly, in which portal and/or mesenteric veins are encased by pancreas tissue. The aim of the study was to determine the role of PAP in pancreatic surgery as well as its management and potential complication, specifically, postoperative pancreatic fistula (POPF). On the basis of a case report, the MEDLINE and ISI Web of Science databases were systematically reviewed up to September 2012. All articles describing a case of PAP were considered. In summary, 21 studies with 59 cases were included. The overall prevalence of PAP was 2.4% and the patients' mean (SD) age was 55.9 (16.2) years. The POPF rate in patients with PAP (12 pancreaticoduodenectomies and 3 distal pancreatectomies) was 46.7% (in accordance with the definition of the International Study Group of Pancreatic Surgery). Portal annular pancreas is a quite unattended pancreatic variant with high prevalence and therefore still remains a clinical challenge to avoid postoperative complications. To decrease the risk for POPF, attentive preoperative diagnostics should also focus on PAP. In pancreaticoduodenectomy, a shift of the resection plane to the pancreas tail should be considered; in extensive pancreatectomy, coverage of the pancreatic remnant by the falciform ligament could be a treatment option. PMID:25207658

  14. Insulin secretion abnormalities in exocrine pancreatic sufficient cystic fibrosis patients.

    PubMed

    Wooldridge, Jamie L; Szczesniak, Rhonda D; Fenchel, Matthew C; Elder, Deborah A

    2015-11-01

    The aim of this study is to assess insulin secretion in pediatric cystic fibrosis (CF) patients with exocrine pancreatic sufficiency. Glucose and insulin responses during an oral glucose tolerance test (OGTT) were measured in 146 CF patients. Patients were divided into exocrine sufficient (CF-PS) and insufficient (CF-PI) groups based on pancreatic enzyme usage and fecal elastase. A reference group included healthy, non-diabetic subjects. All CF groups showed reduced insulin secretion as measured by insulinogenic index. The CF-PS patients had normal glucose tolerance. There was a direct correlation between BMI z-score and insulin area under the curve. Patients with CF have reduced insulin secretion during an OGTT regardless of exocrine pancreatic status. The abnormal insulin secretion in all CF patients may predispose them for glucose intolerance, particularly when challenged by inflammation, infection, or nutritional deficiency. In addition, the diminished insulin secretion may contribute to increased catabolism. Lastly, the CF-related diabetes (CFRD) screening guidelines should be followed by all CF patients regardless of pancreatic status. Copyright © 2015 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

  15. Insulin Secretion Abnormalities in Exocrine Pancreatic Sufficient Cystic Fibrosis Patients

    PubMed Central

    Wooldridge, Jamie L.; Szczesniak, Rhonda D.; Fenchel, Matthew C.; Elder, Deborah A.

    2015-01-01

    BACKGROUND To assess insulin secretion in pediatric cystic fibrosis (CF) patients with exocrine pancreatic sufficiency. METHODS Glucose and insulin responses during an oral glucose tolerance test (OGTT) were measured in 146 CF patients. Patients were divided into exocrine sufficient (CF-PS) and insufficient (CF-PI) groups based on pancreatic enzyme usage and fecal elastase. A reference group included healthy, non-diabetic subjects. RESULTS All CF groups showed reduced insulin secretion as measured by insulinogenic index. The CF-PS patients had normal glucose tolerance. There was direct correlation between BMI z-score and insulin area under the curve. CONCLUSION Patients with CF have reduced insulin secretion during an OGTT regardless of exocrine pancreatic status. The abnormal insulin secretion in all CF patients may predispose them for glucose intolerance, particularly when challenged by inflammation, infection, or nutritional deficiency. In addition, the diminished insulin secretion may contribute to increased catabolism. Lastly, the CF-related diabetes (CFRD) screening guidelines should be followed by all CF patients regardless of pancreatic status. PMID:25754095

  16. Exocrine gastric secretion and gastritis: pathophysiological and clinical relationships.

    PubMed

    Colacci, E; Pasquali, A; Severi, C

    2011-01-01

    Gastric exocrine secretion, both acid and non-acid, is required for micronutrients absorption, such as iron, calcium and vitamin B12, drugs absorption, protein digestion. Clinical presentation of a gastric secretion impairment might be then characterized by the presence of both gastrointestinal and non-gastrointestinal specific symptoms (i.e. anemia) or to a non-response to therapies. The main factor that impairs gastric exocrine secretion homeostasis is mucosal chronic inflammation that principally occurs after colonization by Helicobacter pylori (Hp). The extent and distribution of gastritis ultimately determine the clinical outcome linked to differences in gastric acid secretion status, the involvement of gastric body leading to a decrease in gastric exocrine secretion with possible progression to mucosal atrophy towards cancer. A correct clinical strategy in the management of Hp infected patients should be then to early identify body involvement, a diagnosis generally missed in that body biopsies are not routinely performed. The use of gastric serological markers, gastrin and pepsinogens, are helpful in suspecting the presence of mucosal atrophy but their diagnostic accuracy for non-atrophic chronic gastritis topography is not adequate despite a good specificity due to the low sensitivity, of all the available biomarkers. Gastric serology associated to anemia/iron-deficiency screening might nevertheless been helpful in the framing of patients that undergo endoscopy in order to highlight the need of extensive mucosal biopsies sampling.

  17. Mitochondrial calcium in the life and death of exocrine secretory cells.

    PubMed

    Voronina, Svetlana; Tepikin, Alexei

    2012-07-01

    The remarkable recent discoveries of the proteins mediating mitochondrial Ca(2+) transport (reviewed in this issue) provide an exciting opportunity to utilise this new knowledge to improve our fundamental understanding of relationships between Ca(2+) signalling and bioenergetics and, importantly, to improve the understanding of diseases in which Ca(2+) toxicity and mitochondrial malfunction play a crucial role. Ca(2+) is an important activator of exocrine secretion, a regulator of the bioenergetics of exocrine cells and a contributor to exocrine cell damage. Exocrine secretory cells, exocrine tissues and diseases affecting exocrine glands (like Sjögren's syndrome and acute pancreatitis) will, therefore, provide worthy research areas for the application of this new knowledge of the Ca(2+) transport mechanisms in mitochondria.

  18. Acinar cell carcinoma of the pancreas presenting as diffuse pancreatic enlargement: Two case reports and literature review.

    PubMed

    Luo, Yaping; Hu, Guilan; Ma, Yanru; Guo, Ning; Li, Fang

    2017-09-01

    Pancreatic acinar cell carcinoma (ACC) is a rare malignant tumor of exocrine pancreas. It is typically a well-marginated large solid mass arising in a certain aspect of the pancreas. Diffuse involvement of ACC in the pancreas is very rare, and may simulate pancreatitis in radiological findings. We report 2 cases of ACC presenting as diffuse enlargement of the pancreas due to tumor involvement without formation of a distinct mass. The patients consisted of a 41-year-old man with weight loss and a 77-year-old man who was asymptomatic. Computed tomography (CT) and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT showed diffuse enlargement of the pancreas forming a sausage-like shape with homogenously increased FDG activity. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) biopsy of the pancreatic lesion was performed. Histopathology results from the pancreas confirmed the diagnosis of pancreatic ACC. Because diffuse enlargement of the pancreas is a common imaging feature of pancreatitis, recognition of this rare morphologic pattern of ACC is important for radiological diagnosis of this tumor.

  19. Common Disorders of the Pancreas

    MedlinePlus

    ... Up About Us Board of Directors Newsletter Partners Financial & Privacy Policy Contact Us Patient Information About the Pancreas NPF ... here . About Us Board of Directors Newsletter Partners Financial & Privacy Policy Contact Us Patient Information About the Pancreas Genetics & ...

  20. Two novel GATA6 mutations cause childhood-onset diabetes mellitus, pancreas malformation and congenital heart disease.

    PubMed

    Gong, Maolian; Simaite, Deimante; Kühnen, Peter; Heldmann, Michael; Spagnoli, Francesca; Blankenstein, Oliver; Hübner, Norbert; Hussain, Khalid; Raile, Klemens

    2013-01-01

    GATA6 mutations are the most frequent cause of pancreatic agenesis and diabetes in human sporadic cases. In families, dominantly inherited mutations show a variable phenotype also in terms of endocrine and exocrine pancreatic disease. We report two novel GATA6 mutations in an independent cohort of 8 children with pancreas aplasia or hypoplasia and diabetes. We sequenced GATA6 in 8 children with diabetes and inborn pancreas abnormalities, i.e. hypoplasia or aplasia in which other known candidate genes causing monogenic diabetes and pancreatic defects had been excluded. We found two novel heterozygous GATA6 mutations (c.951_954dup and c.754_904del) in 2 patients with sporadic pancreas hypoplasia, diabetes and severe cardiac defects (common truncus arteriosus and tetralogy of Fallot), but not in the remaining 6 patients. GATA6 mutations in carriers exhibited hypoplastic pancreas with absent head in 1 patient and with increased echogenicity and decreasing exocrine function in the other patient. Additionally, hepatobiliary malformations and brain atrophy were found in 1 patient. Our 2 cases with novel GATA6 mutations add more phenotype characteristics of GATA6 haploinsufficiency. In agreement with an increasing number of published cases, the wide phenotypic spectrum of GATA6 diabetes syndrome should draw the attention of both pediatric endocrinologists and geneticists. Copyright © 2013 S. Karger AG, Basel.

  1. Pseudocyst of the head of the pancreas: relationship to the duct of Santorini.

    PubMed Central

    Anderson, M C

    1979-01-01

    A series of 14 patients with chronic alcoholic pancreatitis is presented which illustrates that cysts originating in the superior segment of the head of the pancreas communicate with the duct of Santorini which normally drains this area of the gland. Cysts in this location do not communicate with the major pancreatic duct (Wirsung) in most instances, and therefore may be overlooked in the standard retrograde drainage procedures employed to relieve pancreatic exocrine obstruction. Images Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. Fig. 9. Fig. 10. Fig. 11. Fig. 12. PMID:518172

  2. Rat pancreas secretes particulate ecto-nucleotidase CD39

    PubMed Central

    Sørensen, Christiane E; Amstrup, Jan; Rasmussen, Hans N; Ankorina-Stark, Ieva; Novak, Ivana

    2003-01-01

    In exocrine pancreas, acini release ATP and the excurrent ducts express several types of purinergic P2 receptors. Thereby, ATP, or its hydrolytic products, might play a role as a paracrine regulator between acini and ducts. The aim of the present study was to elucidate whether this acinar-ductal signalling is regulated by nucleotidase(s), and to characterize and localize one of the nucleotidases within the rat pancreas. Using RT-PCR and Western blotting we show that pancreas expresses the full length ecto-nucleoside triphosphate diphosphohydrolase, CD39. Immunofluorescence shows CD39 localization on basolateral membranes of acini and intracellularly. In small intercalated/ interlobular ducts, CD39 immunofluorescence was localized on the luminal membranes, while in larger ducts it was localized on the basolateral membranes. Upon stimulation with cholecystokinin-octapeptide-8 (CCK-8), acinar CD39 relocalizes in clusters towards the lumen and is secreted. As a result, pancreatic juice collected from intact pancreas stimulated with CCK-8 contained nucleotidase activity, including that of CD39, and no detectable amounts of ATP. Anti-CD39 antibodies detected the full length (78 kDa) CD39 in pancreatic juice. This CD39 was confined only to the particulate and not to the soluble fraction of CCK-8-stimulated secretion. No CD39 activity was detected in secretion stimulated by secretin. The role of secreted particulate, possibly microsomal, CD39 would be to regulate intraluminal ATP concentrations within the ductal tree. In conclusion, we show a novel inducible release of full length particulate CD39, and propose its role in the physiological context of pancreatic secretion. PMID:12832497

  3. Outcome and morbidity of pancreas transplantation in a single Spanish institution.

    PubMed

    Navarro, A; Castro, M J; Cabello, M; Aranda, J M; Burgos, D; Lopez, B; Perez, A; Solas, E

    2006-06-01

    Pancreas transplantation is nowadays the only treatment to reestablish normal blood glucose in diabetic patients. Moreover, transplantation may also prevent and possibly even revert diabetes-related complications. We present our results with the first 4 years of a pancreas transplantation program. From February 2000 to June 2004, we performed 43 pancreas transplants in 42 recipients. In all cases the technique was enteric drainage of the exocrine secretions and systemic venous derivation to the inferior vena cava for endocrine secretions. A simultaneous pancreas-kidney transplant was performed in 37 (88.1%) patients, a pancreas after kidney in 4 (9.5%) patients, and a retransplant in 1 (2.4%) patient. Glycosylated hemoglobin and C peptide returned to normal values in all cases. Patient and graft survivals were 91% and 84%, respectively, after a median follow-up of 19 months. The rate of reoperations was 31% with an overall 16% graft loss. Our results were comparable to those of larger series.

  4. ECM Signaling Regulates Collective Cellular Dynamics to Control Pancreas Branching Morphogenesis.

    PubMed

    Shih, Hung Ping; Panlasigui, Devin; Cirulli, Vincenzo; Sander, Maike

    2016-01-12

    During pancreas development, epithelial buds undergo branching morphogenesis to form an exocrine and endocrine gland. Proper morphogenesis is necessary for correct lineage allocation of pancreatic progenitors; however, the cellular events underlying pancreas morphogenesis are unknown. Here, we employed time-lapse microscopy and fluorescent labeling of cells to analyze cell behaviors associated with pancreas morphogenesis. We observed that outer bud cells adjacent to the basement membrane are pleomorphic and rearrange frequently; additionally, they largely remain in the outer cell compartment even after mitosis. These cell behaviors and pancreas branching depend on cell contacts with the basement membrane, which induce actomyosin cytoskeleton remodeling via integrin-mediated activation of FAK/Src signaling. We show that integrin signaling reduces E-cadherin-mediated cell-cell adhesion in outer cells and provide genetic evidence that this regulation is necessary for initiation of branching. Our study suggests that regulation of cell motility and adhesion by local niche cues initiates pancreas branching morphogenesis. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  5. ECM signaling regulates collective cellular dynamics to control pancreas branching morphogenesis

    PubMed Central

    Shih, Hung Ping; Panlasigui, Devin; Cirulli, Vincenzo; Sander, Maike

    2015-01-01

    Summary During pancreas development, epithelial buds undergo branching morphogenesis to form an exocrine and endocrine gland. Proper morphogenesis is necessary for correct lineage allocation of pancreatic progenitors; however, the cellular events underlying pancreas morphogenesis are unknown. Here, we employed time-lapse microscopy and fluorescent labeling of cells to analyze cell behaviors associated with pancreas morphogenesis. We observed that outer bud cells adjacent to the basement membrane are pleomorphic and rearrange frequently; as well, they largely remain in the outer cell compartment even after mitosis. These cell behaviors and pancreas branching depend on cell contacts with the basement membrane, which induce actomyosin cytoskeleton remodeling via integrin-mediated activation of FAK/Src signaling. We show that integrin signaling reduces E-cadherin-mediated cell-cell adhesion in outer cells, and provide genetic evidence that this regulation is necessary for initiation of branching. Our study suggests that regulation of cell motility and adhesion by local niche cues initiates pancreas branching morphogenesis. PMID:26748698

  6. Development of the chick pancreas with regard to estimation of the relative occurrence and growth of endocrine tissue.

    PubMed

    Manáková, E; Titlbach, M

    2007-04-01

    Endocrine cells in chick pancreas were observed to map their distribution during development and to perform morphometric studies starting on embryonic day 5. The ratio of exocrine to endocrine tissues first prevailed in favour of the endocrine ones, and changed abruptly after day 9 when rapid growth of exocrine tissue began. Endocrine tissue was formed of two types of islets. The 'light' (or B) islets were composed of insulin-immunoreactive cells, completed perhaps by a few somatostatin-immunoreactive cells occurring on the periphery. The majority of the somatostatin- and glucagon-immunoreactive cells were present in the 'dark' (or A) islets. Endocrine elements were also scattered as single cells over the pancreas. Sporadically, the endocrine cells established contacts with exocrine ducts. In morphometric analysis, volume density of insulin-, glucagon-, and somatostatin-immunoreactive cells was measured, and ratios were calculated between particular components. The volume density of endocrine cells and their ratio appeared stable in individual lobes but varied significantly between each other. Increase of the glucagon volume density is exponential, whereas insulin increases almost linearly especially in splenic lobe. The process results in the increase of the hormone-immunoreactive cell volume density in favour of glucagon-immunoreactive cells typical for birds.

  7. Ectopic Ptf1a expression in murine ESCs potentiates endocrine differentiation and models pancreas development in vitro.

    PubMed

    Nair, Gopika G; Vincent, Robert K; Odorico, Jon S

    2014-05-01

    Besides its role in exocrine differentiation, pancreas-specific transcription factor 1a (PTF1a) is required for pancreas specification from the foregut endoderm and ultimately for endocrine cell formation. Examining the early role of PTF1a in pancreas development has been challenging due to limiting amounts of embryonic tissue material for study. Embryonic stem cells (ESCs) which can be differentiated in vitro, and without limit to the amount of experimental material, can serve as a model system to study these early developmental events. To this end, we derived and characterized a mouse ESC line with tetracycline-inducible expression of PTF1a (tet-Ptf1a mESCs). We found that transient ectopic expression of PTF1a initiated the pancreatic program in differentiating ESCs causing cells to activate PDX1 expression in bud-like structures resembling pancreatic primordia in vivo. These bud-like structures also expressed progenitor markers characteristic of a developing pancreatic epithelium. The epithelium differentiated to generate a wave of NGN3+ endocrine progenitors, and further formed cells of all three pancreatic lineages. Notably, the insulin+ cells in the cultures were monohormonal, and expressed PDX1 and NKX6.1. PTF1a-induced cultures differentiated into significantly more endocrine and exocrine cells and the ratio of endocrine-to-exocrine cell differentiation could be regulated by retinoic acid (RA) and nicotinamide (Nic) signaling. Moreover, induced cultures treated with RA and Nic exhibited a modest glucose response. Thus, this tet-Ptf1a ESC-based in vitro system is a valuable new tool for interrogating the role of PTF1a in pancreas development and in directing differentiation of ESCs to endocrine cells.

  8. Tumor-to-tumor metastasis: report of two cases of renal cell carcinoma metastasizing to microcystic serous cystadenoma of the pancreas.

    PubMed

    Shah, Lopa; Tiesi, Gregory; Bamboat, Zubin; McCain, Donald; Siegel, Andrew; Mannion, Ciaran

    2015-02-01

    Metastatic cancer to the pancreas accounts for less than 2% of all pancreatic malignancies. In contrast to other metastatic tumors, renal cell carcinoma (RCC) has a propensity to metastasize as a solitary pancreatic lesion. While symptomatic patients may present with obstructive jaundice, abdominal pain, or gastrointestinal bleeding, the diagnosis of metastatic pancreatic involvement is often made in asymptomatic patients, during follow-up evaluation in the aftermath of an initial diagnosis of renal cell carcinoma. Microcystic serous cystadenoma of the pancreas is an uncommon pancreatic exocrine neoplasm that morphologically resembles conventional (clear cell) RCC, in so far as both tumors are characterized by neoplastic cells with clear cytoplasm, relatively uniform nuclei and scant associated tumor stroma. Herein, we report 2 immunohistochemically confirmed cases of unsuspected metastatic RCC to the pancreas, with the metastatic tumor in each case confined to a preexisting microcystic serous cystadenoma of the pancreas.

  9. A piglet with surgically induced exocrine pancreatic insufficiency as an animal model of newborns to study fat digestion.

    PubMed

    Goncharova, Kateryna; Pierzynowski, Stefan G; Grujic, Danica; Kirko, Siarhei; Szwiec, Katarzyna; Wang, Jing; Kovalenko, Tetiana; Osadchenko, Iryna; Ushakova, Galyna; Shmigel, Halyna; Fedkiv, Olexandr; Majda, Blanka; Prykhodko, Olena

    2014-12-28

    The maldigestion and malabsorption of fat in infants fed milk formula results due to the minimal production of pancreatic lipase. Thus, to investigate lipid digestion and absorption and mimic the situation in newborns, a young porcine exocrine pancreatic insufficient (EPI) model was adapted and validated in the present study. A total of thirteen EPI pigs, aged 8 weeks old, were randomised into three groups and fed either a milk-based formula or a milk-based formula supplemented with either bacterial or fungal lipase. Digestion and absorption of fat was directly correlated with the addition of lipases as demonstrated by a 30% increase in the coefficient of fat absorption. In comparison to the control group, a 40 and 25% reduction in total fat content and 26 and 45% reduction in n-3 and n-6 fatty acid (FA) content in the stool was observed for lipases 1 and 2, respectively. Improved fat absorption was reflected in the blood levels of lipid parameters. During the experiment, only a very slight gain in body weight was observed in EPI piglets, which can be explained by the absence of pancreatic protease and amylase in the gastrointestinal tract. This is similar to newborn babies that have reduced physiological function of exocrine pancreas. In conclusion, we postulate that the EPI pig model fed with infant formula mimics the growth and lipid digestion and absorption in human neonates and can be used to elucidate further importance of fat and FA in the development and growth of newborns, as well as for testing novel formula compositions.

  10. Laparoscopic Biopsies in Pancreas Transplantation.

    PubMed

    Uva, P D; Odorico, J S; Giunippero, A; Cabrera, I C; Gallo, A; Leon, L R; Minue, E; Toniolo, F; Gonzalez, I; Chuluyan, E; Casadei, D H

    2017-08-01

    As there is no precise laboratory test or imaging study for detection of pancreas allograft rejection, there is increasing interest in obtaining pancreas tissue for diagnosis. Pancreas allograft biopsies are most commonly performed percutaneously, transcystoscopically, or endoscopically, yet pancreas transplant surgeons often lack the skills to perform these types of biopsies. We have performed 160 laparoscopic pancreas biopsies in 95 patients. There were 146 simultaneous kidney-pancreas biopsies and 14 pancreas-only biopsies due to pancreas alone, kidney loss, or extraperitoneal kidney. Biopsies were performed for graft dysfunction (89) or per protocol (71). In 13 cases, an additional laparoscopic procedure was performed at the same operation. The pancreas diagnostic tissue yield was 91.2%; however, the pancreas could not be visualized in eight cases (5%) and in 6 cases the tissue sample was nondiagnostic (3.8%). The kidney tissue yield was 98.6%. There were four patients with intraoperative complications requiring laparotomy (2.5%) with two additional postoperative complications. Half of all these complications were kidney related. There were no episodes of pancreatic enzyme leak and there were no graft losses related to the procedure. We conclude that laparoscopic kidney and pancreas allograft biopsies can be safely performed with very high tissue yields. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  11. Impact of Non-Alcoholic Fatty Pancreas Disease on Glucose Metabolism.

    PubMed

    Yu, Tse-Ya; Wang, Chih-Yuan

    2017-03-31

    With increasing global epidemic of obesity, the clinical importance of non-alcoholic fatty pancreas disease (NAFPD) has grown. Even though the pancreas may be more susceptible to ectopic fat deposition compared with the liver, NAFPD was rarely discussed due to the limitation of detecting techniques. In the past, NAFPD was considered as an innocent condition or just part of clinical manifestations during the course of obesity. Recently, a growing body of research suggests that NAFPD may be associated with β-cell dysfunction, insulin resistance, and inflammation, which possibly leads to the development of diabetes and metabolic syndrome. This review summarized the current literature on the epidemiology, potential pathophysiology, diagnostic techniques, impact of NAFPD on β-cell function and insulin resistance, and the clinical relevance of interplay between NAFPD and glucometabolic disorders. This article is protected by copyright. All rights reserved.

  12. Polydopamine--an organocatalyst rather than an innocent polymer.

    PubMed

    Mrówczyński, Radosław; Bunge, Alexander; Liebscher, Jürgen

    2014-07-07

    Polydopamine (PDA) is easily available by oxidation of dopamine and is widely used for persistent coatings of various materials. It is hitherto considered to be inert in many interesting biomedical and other applications. Results presented here, reveal an unexpected behavior of polydopamine as an organocatalyst in direct aldol reactions under mild conditions. Evidence was found for dual catalysis making use of amino and phenolic hydroxy groups found in PDA. Thus scientists must be aware that PDA is not an innocent polymer and can cause unwanted side effects in important applications, such as in biomedicine or as supports in catalysis. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. Ingestion of magnets: innocent in solitude, harmful in groups.

    PubMed

    Wildhaber, Barbara E; Le Coultre, Claude; Genin, Bernard

    2005-10-01

    Foreign body ingestion is frequent in children and generally associated with little morbidity. However, some foreign bodies are innocent when ingested as a single object, but may have harmful effect if numerous. We report a 9-year-old girl who swallowed 5 magnets, causing acute intestinal obstruction. At laparotomy, 2 magnets were found in the cecum and 3 in the transverse colon, attracting each other and clasping a segment of ileum in between, causing a complete obstruction of the small intestine. If numerous magnets are ingested, particular concern is advised, and if signs of intestinal distress develop, prompt laparotomy to prevent serious gastrointestinal complications should be performed.

  14. Stabilised 111In-labelled DTPA- and DOTA-conjugated neurotensin analogues for imaging and therapy of exocrine pancreatic cancer.

    PubMed

    de Visser, M; Janssen, P J J M; Srinivasan, A; Reubi, J C; Waser, B; Erion, J L; Schmidt, M A; Krenning, E P; de Jong, M

    2003-08-01

    Neurotensin (NT) receptors are overexpressed in exocrine pancreatic cancer and Ewing's sarcoma. The potential utility of native NT in cancer diagnosis and therapy is, however, limited by its rapid degradation in vivo. Therefore, NT analogues were synthesised with modified lysine and arginine derivatives to enhance stability and coupled either to DTPA, to enable high specific activity labelling with indium-111 for imaging, or to DOTA, to enable high specific activity labelling with beta-emitting radionuclides, such as lutetium-177 and yttrium-90. Based on serum stability (4 h incubation at 37 degrees C in human serum) and receptor binding affinity, the five most promising analogues were selected and further evaluated in in vitro internalisation studies in human colorectal adenocarcinoma HT29 cells, which overexpress NT receptors. All five NT analogues bound with high affinity to NT receptors on human exocrine pancreatic tumour sections. The analogues could be labelled with (111)In to a high specific activity. The (111)In-labelled compounds were found to be very stable in serum. Incubation of HT29 cells with the (111)In-labelled analogues at 37 degrees C showed rapid receptor-mediated uptake and internalisation. The most promising analogue, peptide 2530 [DTPA-(Pip)Gly-Pro-(PipAm)Gly-Arg-Pro-Tyr-tBuGly-Leu-OH] was further tested in vivo in a biodistribution study using HT29 tumour-bearing nude mice. The results of this study showed low percentages of injected dose per gram tissue of this (111)In-labelled 2530 analogue in receptor-negative organs like blood, spleen, pancreas, liver, muscle and femur. Good uptake was found in the receptor-positive HT29 tumour and high uptake was present in the kidneys. Co-injection of excess unlabelled NT significantly reduced tumour uptake, showing that tumour uptake is a receptor-mediated process. With their enhanced stability, maintained high receptor affinity and rapid receptor-mediated internalisation, the (111)In-labelled DTPA

  15. Response to long-term enzyme replacement treatment in dogs with exocrine pancreatic insufficiency.

    PubMed

    Wiberg, M E; Lautala, H M; Westermarck, E

    1998-07-01

    To study response to long-term enzyme replacement treatment in dogs with exocrine pancreatic insufficiency (EPI). Cross-sectional study. 76 German Shepherd Dogs or rough-coated Collies with EPI and 145 clinically normal dogs of the same breeds. Questionnaires were sent to owners of dogs with EPI and owners of clinically normal dogs. Dogs with EPI had been given dietary enzyme supplements for at least 4 months. Relative frequency distributions of gastrointestinal tract and dermatologic signs, prevalences of typical signs of EPI (e.g., weight loss, ravenous appetite, yellow and pulpy feces, high fecal volume), feeding regimens, and dietary intolerances were compared between dogs with EPI and clinically normal dogs. Gastrointestinal tract signs considered typical for dogs with EPI were almost completely controlled with dietary enzyme supplements in half of the dogs with EPI, and their general health was similar to that of clinically normal dogs. A poor treatment response was found in a fifth of dogs with EPI that had several signs that were typical of EPI. Signs most often persisting were high fecal volume, yellow and pulpy feces, and flatulence. Dermatologic problems were common, especially in German Shepherd Dogs with EPI. Treatment response was irrespective of breed. Nonenteric-coated enzyme supplements, powdered enzyme, and raw chopped pancreas were equally effective in controlling clinical signs. Although dietary sensitivities were common, use of adjunctive dietary treatment was minimal. Antibiotics were occasionally administered to half of the dogs with EPI. Results of this study indicate that, with basically similar treatment regimens, response to long-term enzyme treatment in dogs with EPI varied considerably.

  16. Effects of phorbol ester on cholecystokinin octapeptide-evoked exocrine pancreatic secretion in the rat.

    PubMed Central

    Francis, L P; Camello, P J; Singh, J; Salido, G M; Madrid, J A

    1990-01-01

    1. A comparative study was made of the effect of the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA) on cholecystokinin octapeptide-evoked exocrine pancreatic secretion in the anaesthetized rat and isolated permeabilized pancreatic acinar cells. 2. Cholecystokinin octapeptide (CCK8; 0.10-6.40 nmol (kg body weight)-1) induced dose-dependent increases in pancreatic juice flow, total protein output and amylase release in the anaesthetized rat. 3. Administration of TPA (10(-8) mol (kg body weight)-1) in combination with CCK8 resulted in marked attenuation of the CCK8-evoked secretory response. 4. Simultaneous injection of polymyxin B (10(-8) mol (kg body weight)-1), an inhibitor of protein kinase C, with TPA and CCK8 reversed the inhibitory effect of the phorbol ester on CCK8-induced pancreatic juice flow, total protein output and amylase release. 5. In permeabilized rat pancreatic acini CCK8 (10(-13)-10(-9) M) elicited dose-dependent increases in [3H]leucine-labelled protein secretion (3H-labelled protein release). Combining TPA (10(-8) M) with CCK8 resulted in an inhibition of the CCK8-induced 3H-labelled protein release especially at lower concentrations of CCK8. At higher concentrations of CCK8, TPA was unable to inhibit the CCK8-evoked 3H-labelled protein release. Again, polymyxin B reversed the TPA-induced inhibition of CCK8-evoked 3H-labelled protein output. 6. The results indicate that protein kinase C activation may play an important physiological role in modulating the CCK8-evoked secretory response in rat pancreas in vivo and in vitro. PMID:1712842

  17. Structural similarities and differences between the human and the mouse pancreas.

    PubMed

    Dolenšek, Jurij; Rupnik, Marjan Slak; Stožer, Andraž

    2015-01-01

    Mice remain the most studied animal model in pancreas research. Since the findings of this research are typically extrapolated to humans, it is important to understand both similarities and differences between the 2 species. Beside the apparent difference in size and macroscopic organization of the organ in the 2 species, there are a number of less evident and only recently described differences in organization of the acinar and ductal exocrine tissue, as well as in the distribution, composition, and architecture of the endocrine islets of Langerhans. Furthermore, the differences in arterial, venous, and lymphatic vessels, as well as innervation are potentially important. In this article, the structure of the human and the mouse pancreas, together with the similarities and differences between them are reviewed in detail in the light of conceivable repercussions for basic research and clinical application.

  18. Structural similarities and differences between the human and the mouse pancreas

    PubMed Central

    Dolenšek, Jurij; Rupnik, Marjan Slak; Stožer, Andraž

    2015-01-01

    Mice remain the most studied animal model in pancreas research. Since the findings of this research are typically extrapolated to humans, it is important to understand both similarities and differences between the 2 species. Beside the apparent difference in size and macroscopic organization of the organ in the 2 species, there are a number of less evident and only recently described differences in organization of the acinar and ductal exocrine tissue, as well as in the distribution, composition, and architecture of the endocrine islets of Langerhans. Furthermore, the differences in arterial, venous, and lymphatic vessels, as well as innervation are potentially important. In this article, the structure of the human and the mouse pancreas, together with the similarities and differences between them are reviewed in detail in the light of conceivable repercussions for basic research and clinical application. PMID:26030186

  19. The endocrine pancreas of the Cape fur seal, Arctocephalus pusillus (Schreber, 1776): an immunocytochemical study.

    PubMed

    Erasmus, C P; Van Aswegen, G

    1997-09-01

    The indirect peroxidase method was employed to study the endocrine pancreas of the Cape fur seal. Immunoreactivity to insulin was confined to the cores of the islets and the insulin cells were more abundant than the other endocrine cell types, which occurred mainly in the mantles of the islets. Of these, glucagon cells were the most numerous, followed by somatostatin and pancreatic polypeptide (PP) cells. The latter were observed in the mantles of the islets and scattered in the exocrine tissue of the duodenal lobe. The marked variation in the shape and the distribution of the endocrine cells in the mantles of the islets seen in the pancreas of the seal, seems to be typical of carnivorous species like the cat and dog.

  20. Acinar neoplasms of the pancreas-A summary of 25 years of research.

    PubMed

    Klimstra, David S; Adsay, Volkan

    2016-09-01

    Our understanding about the family of acinar neoplasms of the pancreas has grown substantially over the past 25 years. The prototype is acinar cell carcinoma, an uncommon variant of pancreatic carcinoma that demonstrates production of pancreatic exocrine enzymes, verifiable using immunohistochemistry, and exhibits characteristic histologic features. Related neoplasms include mixed acinar carcinomas such as mixed acinar neuroendocrine carcinoma and mixed acinar ductal carcinoma. In the pediatric age group, pancreatoblastoma is also closely related. Cystic and extrapancreatic forms have been described. These neoplasms share molecular alterations that are distinct from the more common ductal and neuroendocrine neoplasms of the pancreas. Although there is a broad range of genetic findings, a number of potential therapeutic targets have emerged. This review explores the clinical and pathologic features of pancreatic acinar neoplasms along with their more common molecular phenotypes. The differential diagnosis with other pancreatic neoplasms is explored as well.

  1. Brilliance of a Fire: Innocence, Experience and the Theory of Childhood

    ERIC Educational Resources Information Center

    Davis, Robert A.

    2011-01-01

    This essay offers an extensive rehabilitation and reappraisal of the concept of childhood innocence as a means of testing the boundaries of some prevailing constructions of childhood. It excavates in detail some of the lost histories of innocence in order to show that these are more diverse and more complex than established and pejorative…

  2. White Innocence and Mexican Americans as Perpetrators in the School-to-Prison Pipeline

    ERIC Educational Resources Information Center

    Orozco, Richard

    2013-01-01

    This essay discusses white innocence as a mechanism that may contribute to perceptions of Mexican Americans as perpetrators. These perceptions are crucial to ways teachers and administrators respond to student actions as the initial steps in the school-to-prison pipeline. Specifically, this work reviews the rhetoric of white innocence in a high…

  3. Brilliance of a Fire: Innocence, Experience and the Theory of Childhood

    ERIC Educational Resources Information Center

    Davis, Robert A.

    2011-01-01

    This essay offers an extensive rehabilitation and reappraisal of the concept of childhood innocence as a means of testing the boundaries of some prevailing constructions of childhood. It excavates in detail some of the lost histories of innocence in order to show that these are more diverse and more complex than established and pejorative…

  4. White Innocence and Mexican Americans as Perpetrators in the School-to-Prison Pipeline

    ERIC Educational Resources Information Center

    Orozco, Richard

    2013-01-01

    This essay discusses white innocence as a mechanism that may contribute to perceptions of Mexican Americans as perpetrators. These perceptions are crucial to ways teachers and administrators respond to student actions as the initial steps in the school-to-prison pipeline. Specifically, this work reviews the rhetoric of white innocence in a high…

  5. Evolution of pancreas in aging: degenerative variation or early changes of disease?

    PubMed

    Chantarojanasiri, Tanyaporn; Hirooka, Yoshiki; Ratanachu-Ek, Thawee; Kawashima, Hiroki; Ohno, Eizaburo; Goto, Hidemi

    2015-04-01

    Pancreatic changes in aging have been described for many decades. They involve not only pancreatic parenchyma but also pancreatic ductal, microscopic, and exocrine functional changes. There have been many studies of these changes based on pathology and various imaging modalities, as well as functional studies. The pancreatic volume was found to decrease with advancing age, with a higher incidence of pancreatic steatosis, as demonstrated in autopsy and imaging studies. The pancreatic ductal structure has been described with wide ranges of normal variation, but many studies have shown a tendency toward enlargement with advancing age. By endoscopic ultrasound imaging, the aging pancreas may exhibit abnormal findings similar to chronic pancreatitis. Microscopically, there has been evidence of patchy lobular fibrosis and papillary hyperplasia and demonstrable k-ras mutation in both normal and dysplastic ductal mucosa. The evidence of pancreatic exocrine insufficiency has yielded conflicting results, but most studies have shown a tendency toward decreased pancreatic exocrine function in the elderly. Differentiating pancreatic change in the elderly from early chronic pancreatitis may be difficult as there are limited studies to compare these two conditions in terms of structural and functional changes.

  6. Role of Connexins and Pannexins in the Pancreas.

    PubMed

    Cigliola, Valentina; Allagnat, Florent; Berchtold, Lukas Adrian; Lamprianou, Smaragda; Haefliger, Jacques-Antoine; Meda, Paolo

    2015-11-01

    The pancreas produces enzymes with a digestive function and hormones with a metabolic function, which are produced by distinct cell types of acini and islets, respectively. Within these units, secretory cells coordinate their functioning by exchanging information via signals that flow in the intercellular spaces and are generated either at distance (several neural and hormonal inputs) or nearby the pancreatic cells themselves (inputs mediated by membrane ionic-specific channels and by ionic- and metabolite-permeant pannexin channels and connexin "hemichannels"). Pancreatic secretory cells further interact via the extracellular matrix of the pancreas (inputs mediated by integrins) and directly with neighboring cells, by mechanisms that do not require extracellular mediators (inputs mediated by gap and tight junction channels). Here, we review the expression and function of the connexins and pannexins that are expressed by the main secretory cells of the exocrine and endocrine pancreatic cells. Available data show that the patterns of expression of these proteins differ in acini and islets, supporting distinct functions in the physiological secretion of pancreatic enzymes and hormones. Circumstantial evidence further suggests that alterations in the signaling provided by these proteins are involved in pancreatic diseases.

  7. Endothelium-derived essential signals involved in pancreas organogenesis

    PubMed Central

    Talavera-Adame, Dodanim; Dafoe, Donald C

    2015-01-01

    Endothelial cells (ECs) are essential for pancreas differentiation, endocrine specification, and endocrine function. They are also involved in the physiopathology of type 1 and type 2 diabetes. During embryogenesis, aortic ECs provide specific factors that maintain the expression of key genes for pancreas development such as pancreatic and duodenal homeobox-1. Other unknown factors are also important for pancreatic endocrine specification and formation of insulin-producing beta cells. Endocrine precursors proliferate interspersed with ductal cells and exocrine precursors and, at some point of development, these endocrine precursors migrate to pancreatic mesenchyme and start forming the islets of Langerhans. By the end of the gestation and close to birth, these islets contain immature beta cells with the capacity to express vascular endothelial growth factor and therefore to recruit ECs from the surrounding microenvironment. ECs in turn produce factors that are essential to maintain insulin secretion in pancreatic beta cells. Once assembled, a cross talk between endocrine cells and ECs maintain the integrity of islets toward an adequate function during the whole life of the adult individual. This review will focus in the EC role in the differentiation and maturation of pancreatic beta cells during embryogenesis as well as the current knowledge about the involvement of endothelium to derive pancreatic beta cells in vitro from mouse or human pluripotent stem cells. PMID:25992319

  8. Pancreas transplantation. An immunohistologic and histopathologic examination of 100 grafts.

    PubMed Central

    Sibley, R. K.; Sutherland, D. E.

    1987-01-01

    The authors examined tissues obtained by biopsy, pancreatectomy, and autopsy from 100 pancreas grafts to determine the cause of dysfunction or failure of the graft. Immunohistologic examination of 42 tissues to determine the mononuclear cell phenotypes and Class I and II antigen expression was performed as well. Technical factors--infections, thrombosis, obstruction--accounted for a large number of graft losses, but immunologic-mediated mechanisms resulted in graft dysfunction and failure as well. Pleomorphic inflammatory infiltrates were present in grafts with acute rejection, as well as Silastic and Prolamine duct-obstructed grafts. Criteria useful in the identification of acute rejection from pancreatitis included a more intense, predominantly mononuclear cell infiltration of transformed lymphocytes in the exocrine pancreas and evidence of vascular rejection--endovasculitis or fibrinoid necrosis. Increased expression and/or induction of Class I and II antigens on pancreatic constituents occurred in grafts with evidence of acute rejection, but also with Silastic and prolamine duct-obstructed pancreatitis. An isletitis occurred in 25% of the grafts. Nine of the 25 grafts (36%) with isletitis also had selective loss of beta cells from the islets. Recurrent diabetes mellitus appeared to have developed in these cases, which accounted for loss of graft function. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 PMID:3037911

  9. The essence of innocence: consequences of dehumanizing Black children.

    PubMed

    Goff, Phillip Atiba; Jackson, Matthew Christian; Di Leone, Brooke Allison Lewis; Culotta, Carmen Marie; DiTomasso, Natalie Ann

    2014-04-01

    The social category "children" defines a group of individuals who are perceived to be distinct, with essential characteristics including innocence and the need for protection (Haslam, Rothschild, & Ernst, 2000). The present research examined whether Black boys are given the protections of childhood equally to their peers. We tested 3 hypotheses: (a) that Black boys are seen as less "childlike" than their White peers, (b) that the characteristics associated with childhood will be applied less when thinking specifically about Black boys relative to White boys, and (c) that these trends would be exacerbated in contexts where Black males are dehumanized by associating them (implicitly) with apes (Goff, Eberhardt, Williams, & Jackson, 2008). We expected, derivative of these 3 principal hypotheses, that individuals would perceive Black boys as being more responsible for their actions and as being more appropriate targets for police violence. We find support for these hypotheses across 4 studies using laboratory, field, and translational (mixed laboratory/field) methods. We find converging evidence that Black boys are seen as older and less innocent and that they prompt a less essential conception of childhood than do their White same-age peers. Further, our findings demonstrate that the Black/ape association predicted actual racial disparities in police violence toward children. These data represent the first attitude/behavior matching of its kind in a policing context. Taken together, this research suggests that dehumanization is a uniquely dangerous intergroup attitude, that intergroup perception of children is underexplored, and that both topics should be research priorities.

  10. Ca²⁺-dependent K⁺ channels in exocrine salivary glands.

    PubMed

    Catalán, Marcelo A; Peña-Munzenmayer, Gaspar; Melvin, James E

    2014-06-01

    In the last 15 years, remarkable progress has been realized in identifying the genes that encode the ion-transporting proteins involved in exocrine gland function, including salivary glands. Among these proteins, Ca(2+)-dependent K(+) channels take part in key functions including membrane potential regulation, fluid movement and K(+) secretion in exocrine glands. Two K(+) channels have been identified in exocrine salivary glands: (1) a Ca(2+)-activated K(+) channel of intermediate single channel conductance encoded by the KCNN4 gene, and (2) a voltage- and Ca(2+)-dependent K(+) channel of large single channel conductance encoded by the KCNMA1 gene. This review focuses on the physiological roles of Ca(2+)-dependent K(+) channels in exocrine salivary glands. We also discuss interesting recent findings on the regulation of Ca(2+)-dependent K(+) channels by protein-protein interactions that may significantly impact exocrine gland physiology.

  11. Retinoids in the pancreas

    PubMed Central

    Brun, Pierre-Jacques; Wongsiriroj, Nuttaporn

    2016-01-01

    Retinoids (vitamin A and its natural and synthetic analogs) are required by most tissues for maintaining the normal health of the tissue. This is certainly true for the pancreas. The recent literature is convincing that retinoids are needed by the adult to assure normal pancreatic endocrine functions, especially those of the α- and β-cells. It is also well established that retinoids are required to insure normal pancreas development in utero, including the development of the endocrine pancreas. The actions of retinoids for maintaining normal pancreatic islet functions has drawn considerable research interest from investigators interested in understanding and treating metabolic disease. Pancreatic retinoids are also of interest to investigators studying the origins of pancreatic disease, including the development of pancreatic fibrosis and its sequelae. This research interest is focused on pancreatic stellate cells (PSCs) which store retinoids and possess the metabolic machinery needed to metabolize retinoids. The literature on pancreatic disease and retinoids suggests that there is an association between impairments in pancreatic retinoid storage and metabolism and the development of pancreatic disease. These topics will be considered in this review. PMID:26904552

  12. Postprandial Symptoms Felt at the Lower Part of the Epigastrium and a Possible Association of Pancreatic Exocrine Dysfunction with the Pathogenesis of Functional Dyspepsia

    PubMed Central

    Fujikawa, Yoshiko; Tominaga, Kazunari; Tanaka, Fumio; Kamata, Noriko; Yamagami, Hirokazu; Tanigawa, Tetsuya; Watanabe, Toshio; Fujiwara, Yasuhiro; Arakawa, Tetsuo

    2017-01-01

    Objective In symptom-dependent diseases such as functional dyspepsia (FD), matching the pattern of epigastric symptoms, including severity, kind, and perception site, between patients and physicians is critical. Additionally, a comprehensive examination of the stomach, duodenum, and pancreas is important for evaluating the origin of such symptoms. Methods FD-specific symptoms (epigastric pain, epigastric burning, early satiety, and postprandial fullness) and other symptoms (regurgitation, nausea, belching, and abdominal bloating) as well as the perception site of the above symptoms were investigated in healthy subjects using a new questionnaire with an illustration of the human body. A total of 114 patients with treatment-resistant dyspeptic symptoms were evaluated for their pancreatic exocrine function using N-benzoyl-L-tyrosyl-p-aminobenzoic acid. Results A total of 323 subjects (men:women, 216:107; mean age, 52.1 years old) were initially enrolled. Most of the subjects felt the FD-specific symptoms at the epigastrium, while about 20% felt them at other abdominal sites. About 30% of expressed as epigastric symptoms were FD-nonspecific symptoms. At the epigastrium, epigastric pain and epigastric burning were mainly felt at the upper part, and postprandial fullness and early satiety were felt at the lower part. The prevalence of patients with pancreatic exocrine dysfunction was 71% in the postprandial fullness group, 68% in the epigastric pain group, and 82% in the diarrhea group. Conclusion We observed mismatch in the perception site and expression between the epigastric symptoms of healthy subjects and FD-specific symptoms. Postprandial symptoms were often felt at the lower part of the epigastrium, and pancreatic exocrine dysfunction may be involved in the FD symptoms, especially for treatment-resistant dyspepsia patients. PMID:28674349

  13. Interstitial cells of Cajal in pancreas.

    PubMed

    Popescu, L M; Hinescu, M E; Ionescu, N; Ciontea, Sanda M; Cretoiu, D; Ardelean, Carmen

    2005-01-01

    We show here (presumably for the first time) a special type of cell in the human and rat exocrine pancreas. These cells have phenotypic characteristics of the enteric interstitial cells of Cajal (ICC). To identify pancreatic interstitial cells of Cajal (pICC) we used routine light microscopy, non-conventional light microscopy (less than 1 mum semi-thin sections of Epon-embedded specimens cut by ultramicrotomy and stained with Toluidine blue), transmission electron microscopy (TEM), and immunocytochemistry. The results showed that pICC can be recognized easily by light microscopy, particularly on semi-thin sections, as well as by TEM. Two-dimensional reconstructions from serial photos suggest a network-like spatial distribution of pICC. pICC represent 3.3+/-0.5% of all pancreatic cells, and seem to establish close spatial relationships with: capillaries (43%), acini (40%), stellate cells (14%), nerve fibres (3%). Most of pICC (88%) have 2 or 3 long processes (tens of mum) emerging from the cell body. TEM data show that pICC meet the criteria for positive diagnosis as ICC (e.g. numerous mitochondria, 8.7+/-0.8% of cytoplasm). Immunocytochemistry revealed that pICC are CD117/c-kit and CD34 positive. We found pICC positive (40-50%) for smooth muscle alpha-actin or S-100, and, occasionally, for CD68, NK1 neurokinin receptor and vimentin. The reactions for desmin and chromogranin A were negative in pICC. At present, only hypotheses and speculations can be formulated on the possible role of the pICC (e.g., juxtacrine and/or paracrine roles). In conclusion, the quite-established dogma: "ICC only in cavitary organs" is overpassed.

  14. Transepithelial Bicarbonate Secretion: Lessons from the Pancreas

    PubMed Central

    Park, Hyun Woo; Lee, Min Goo

    2012-01-01

    Many cystic fibrosis transmembrane conductance regulator (CFTR)-expressing epithelia secrete bicarbonate (HCO3−)-containing fluids. Recent evidence suggests that defects in epithelial bicarbonate secretion are directly involved in the pathogenesis of cystic fibrosis, in particular by building up hyperviscous mucus in the ductal structures of the lung and pancreas. Pancreatic juice is one of the representative fluids that contain a very high concentration of bicarbonate among bodily fluids that are secreted from CFTR-expressing epithelia. We introduce up-to-date knowledge on the basic principles of transepithelial bicarbonate transport by showing the mechanisms involved in pancreatic bicarbonate secretion. The model of pancreatic bicarbonate secretion described herein may also apply to other exocrine epithelia. As a central regulator of bicarbonate transport at the apical membrane, CFTR plays an essential role in both direct and indirect bicarbonate secretion. The major role of CFTR in bicarbonate secretion would be variable depending on the tissue and cell type. For example, in epithelial cells that produce a low concentration of bicarbonate-containing fluid (up to 80 mm), either CFTR-dependent Cl−/HCO3− exchange or CFTR anion channel with low bicarbonate permeability would be sufficient to generate such fluid. However, in cells that secrete high-bicarbonate-containing fluids, a highly selective CFTR bicarbonate channel activity is required. Therefore, understanding the molecular mechanism of transepithelial bicarbonate transport and the role of CFTR in each specific epithelium will provide therapeutic strategies to recover from epithelial defects induced by hyposecretion of bicarbonate in cystic fibrosis. PMID:23028131

  15. Pancreatic endocrine responses to nutrients and bombesin after segmental pancreas autotransplantation in dogs.

    PubMed

    Dupre, J; Grace, D M; McDonald, T J; Inculet, R; Leblanc, B

    1987-01-01

    The capacity of autotransplanted (ATP) distal pancreas segments with systemic venous and peritoneal exocrine drainage to support physiologic control of plasma glucose levels was tested, and compared with the functions of "simulated autotransplants" (SATP) prepared with similar dissection and peritoneal exocrine drainage, but with hepatic portal venous drainage, in dogs. In ATP in the postabsorptive state, plasma levels of glucose, immunoreactive insulin (IRI) and immunoreactive glucagon (IRG1) were normal. Autotransplants resulted in impaired glucose tolerance after meals with impaired early insulin responses, and the normal brisk rise of IRG1 in the plasma was delayed and reduced through the first 30 min of feeding. In ATP, also, the response to bombesin was abnormal; the normal stimulation of release of both IRI and IRG1 was delayed in both cases. In studies of responses to oral and intravenous glucose in ATP and SATP dogs, similar mild degrees of glucose intolerance were found with both routes of administration; however, whereas in ATP dogs increases of IRI were highly exaggerated with both routes of administration of glucose, in SATP dogs plasma IRI rose from subnormal levels in the postabsorptive state through subnormal increments with both routes of administration. Further studies are necessary to determine the relative importance of denervation and reduction of the mass of the pancreas in these effects, and to assess the significance of the differences in blood insulin levels in the two preparations.

  16. Light and electron microscopy of neuropeptide Y-containing nerves in human liver, gallbladder, and pancreas.

    PubMed

    Ding, W G; Fujimura, M; Mori, A; Tooyama, I; Kimura, H

    1991-10-01

    Neuropeptide Y-containing nerve fibers were identified by light and electron microscopic immunocytochemistry in the human liver, gallbladder, and pancreas. In the liver, neuropeptide Y-containing nerve fibers were distributed richly in Glisson's sheath and were prominent around the walls of the interlobular vein, interlobular hepatic artery, and hepatic bile duct. The fibers also formed a dense network surrounding the hepatocytes. The nerve terminals were found close to the endothelial cells of blood vessels, as well as being distributed in Disse's space, where they appeared to terminate. Occasionally these terminals contacted directly the membrane of a hepatocyte. In the gallbladder, neuropeptide Y fibers were found in each layer, with an especially dense network in the lamina propria. The fibers also ran close to the epithelium and parallel to the muscle bundles. Blood vessels throughout the gallbladder were well supplied with such nerve fibers. In the pancreas, neuropeptide Y fibers were found mainly near blood vessels and partly in gaps between exocrine glands, seeming to terminate on certain endocrine cells. Nerve terminals were located in the vascular walls and adjacent to the surface of exocrine acinar cells. These studies provide a basis for correlating the neuropeptide Y distribution with pharmacological and physiological studies in humans.

  17. The types of endocrine cells in the pancreas of Sunda porcupine (Hystrix javanica)

    PubMed Central

    Budipitojo, Teguh; Fibrianto, Yuda Heru; Mulyani, Guntari Titik

    2016-01-01

    Aim: To identify the types of endocrine cells in the pancreas of the Sunda porcupine (Hystrix javanica) and its immunolocalization. Materials and Methods: Five adult H. javanica were used without sexual distinction. The presences of endocrine cells (glucagon, insulin, somatostatin, and pancreatic polypeptide [PP]) in pancreatic tissues were detected using the avidin-biotin-peroxidase complex method. Results: The fusiform, round, and oval form endocrine cells were detected in the islets of Langerhans and exocrine parts. Most of the insulin cells were found in the central area, glucagon cells were identified in the central and peripheral areas, and somatostatin and PP cells were detected in the mantle area of the islets of Langerhans. Glucagon and somatostatin cells were also detected in smaller numbers of peripheral parts of the islet. In all of the islet parts, glucagon endocrine cells were most prevalent cell type and then, somatostatin, insulin, and PP. In the exocrine parts, PP, somatostatin, glucagon, and insulin endocrine cells were found in the inter-acinus part with moderate, moderate, a few and rare numbers, in that order. In the pancreatic duct, glucagon and somatostatin cells were found between epithelial cells in rare numbers. Conclusion: The pancreas of Sunda porcupine (H. javanica) contains four types of major pancreatic endocrine cells with approximately similar distribution patterns to the other rodents, except for abundant glucagon cells in the peripheral area of the islets of Langerhans. PMID:27397977

  18. Renal and segmental pancreatic grafting with draining of exocrine secretion and initial continuous intravenous cyclosporin A in a patient with insulin-dependent diabetes and renal failure

    PubMed Central

    Calne, R Y; White, D J G; Rolles, K; Duffy, T J; Kass, T

    1982-01-01

    A patient with renal failure and insulin-dependent diabetes received renal and segmental pancreatic allografts from the same donor, with exocrine drainage of the pancreas being directed into the bowel. An attempt was made to maintain the serum concentrations of cyclosporin A between 300 and 1000 μg/l to avoid serious nephrotoxicity and rejection. Considerable difficulty was experienced in controlling the serum concentrations even with continuous intravenous infusion. When the concentrations were maintained between 300 and 1000 μg/l function in both allografts was satisfactory. At seven months the patient required no insulin and had good renal function. He was not receiving corticosteroids. ImagesFIG 1 PMID:6809184

  19. The left-sided pancreas

    SciTech Connect

    Dunn, G.D.; Gibson, R.N.

    1986-06-01

    Ultrasonography (US) performed in nine patients (two with pancreatic carcinoma, one with hepatomegaly), six with no relevant abdominal disease) showed the pancreas to lie wholly to the left of the aorta. This not uncommon location may give rise to difficulty in demonstrating the pancreas on real-time US scans. The superior mesenteric vessels and splenic vein remain useful land-marks for locating the head of the pancreas in this position.

  20. Interferon Regulatory Factor 6 Is Necessary for Salivary Glands and Pancreas Development.

    PubMed

    Metwalli, K A; Do, M A; Nguyen, K; Mallick, S; Kin, K; Farokhnia, N; Jun, G; Fakhouri, W D

    2017-09-01

    Interferon regulatory factor 6 ( IRF6) acts as a tumor suppressor and controls cell differentiation in ectodermal and craniofacial tissues by regulating expression of target genes. Haploinsufficiency of IRF6 causes Van der Woude and popliteal pterygium syndrome, 2 syndromic forms of cleft lip and palate. Around 85% of patients with Van der Woude express pits on the lower lip that continuously or intermittently drain saliva, and patients with the common cleft lip and palate have a higher prevalence of dental caries and gingivitis. This study aims to identify the role of IRF6 in development of exocrine glands, specifically the major salivary glands. Our transgenic mouse model that expresses LacZ reporter under the control of the human IRF6 enhancer element showed high expression of IRF6 in major and minor salivary glands and ducts. Immunostaining data also confirmed the endogenous expression of IRF6 in the developing ductal, serous, and mucous acinar cells of salivary glands. As such, we hypothesized that Irf6 is important for proper development of salivary glands and potentially other exocrine glands. Loss of Irf6 in mice causes an increase in the proliferation level of salivary cells, disorganized branching morphogenesis, and a lack of differentiated mucous acinar cells in submandibular and sublingual glands. Expression and localization of the acinar differentiation marker MIST1 were altered in Irf6-null salivary gland and pancreas. The RNA-Seq analysis demonstrated that 168 genes are differentially expressed and confer functions associated with transmembrane transporter activity, spliceosome, and transcriptional regulation. Furthermore, expression of genes involved in the EGF pathway-that is, Ereg, Ltbp4, Matn1, Matn3, and Tpo-was decreased at embryonic day 14.5, while levels of apoptotic proteins were elevated at postnatal day 0. In conclusion, our data report a novel role of Irf6 in exocrine gland development and support a rationale for performing exocrine

  1. MR imaging of the pancreas.

    PubMed

    O'Neill, Erin; Hammond, Nancy; Miller, Frank H

    2014-07-01

    Magnetic resonance (MR) imaging of the pancreas is useful as both a problem-solving tool and an initial imaging examination of choice. With newer imaging sequences such as diffusion-weighted imaging, MR offers improved ability to detect and characterize lesions and identify and stage tumors and inflammation. MR cholangiopancreatography can be used to visualize the pancreatic and biliary ductal system. In this article, the use of MR to evaluate the pancreas, including recent advances, is reviewed and the normal appearance of the pancreas on different imaging sequences, as well as inflammatory diseases, congenital abnormalities, and neoplasms of the pancreas, are discussed.

  2. The world is not fair: an examination of innocent and guilty suspects' waiver decisions.

    PubMed

    Scherr, Kyle C; Franks, Andrew S

    2015-04-01

    Suspects' decisions to waive or invoke their interrogation rights can have a considerable impact on their eventual legal fate. Although innocent and guilty suspects show differences in waiver rates, research has yet to examine whether innocent and guilty individuals' waiver decisions are differentially influenced by dispositional and situational factors. The current research examined the relationship among a dispositional factor (just world beliefs), a situational factor (social proof pressures-i.e., influencing others to believe that certain behaviors are normative) and innocent and guilty individuals' waiver decisions. Social proof pressures influenced the preinterrogation decisions of guilty individuals holding strong just world beliefs but not guilty individuals holding weak just world beliefs. However, social proof pressures influenced the preinterrogation decisions of innocent individuals holding weak just world beliefs but not innocent individuals holding strong just world beliefs. Results also indicated that strong just world beliefs are associated with attenuated stress responses to an accusation among innocent individuals but exacerbated stress responses among guilty individuals, thereby helping to explain why guilty and innocent individuals are differentially influenced by situational and dispositional factors. The theoretical and applied implications of these effects are discussed with an emphasis on the consequences of suspects' mindset during the preinterrogation decision-making process.

  3. Cytomegalovirus infection of the graft duodenum and urinary bladder after simultaneous pancreas-kidney transplantation.

    PubMed

    Jang, H J; Kim, S C; Cho, Y P; Kim, Y H; Han, M S; Han, D J

    2004-09-01

    Cytomegalovirus (CMV) is an important cause of morbidity after solid organ transplantation. We report a case of CMV infection involving the transplanted duodenum that developed after simultaneous pancreas-kidney transplantation. The patient, a 30-year-old woman with insulin-dependent diabetes undergoing hemodialysis due to chronic renal failure, received a simultaneous cadaveric pancreas-kidney transplantation. The exocrine secretion was diverted using bladder drainage. Immunosuppression was maintained by a combination of tacrolimus, mycophenolate mofetil, and steroids together with OKT3 induction. Both the donor and the recipient were serologically positive for CMV IgG CMV prophylaxis consisted of a short course of parenteral gancyclovir. The patient was discharged on postoperative day 39 with normal pancreas and kidney function. She presented 2 months after transplantation with hematuria. Cystoscopic pancreas allograft biopsy specimens showed evidence of tissue invasive CMV infection in the graft duodenum and bladder. The CMV antigenemia test was positive. At 4 months after transplantation, the patient underwent surgery with the diagnosis of acute abdomen. The surgical findings consisted of a diffuse acute purulent peritonitis due to perforation of the duodenal graft. We sutured the perforation with nonreabsorbable material. The CMV antigenemia test was negative. Eight days later, the patient developed massive hematuria. At surgery, the graft was removed. The patient was discharged from the hospital with normal renal function. Pathological study of the removed graft showed the duodenal segment to have multiple wide ulcers with CMV inclusions in epithelial cells.

  4. Large Gliadin Peptides Detected in the Pancreas of NOD and Healthy Mice following Oral Administration

    PubMed Central

    Sidenius, Ulrik; Heegaard, Niels H.

    2016-01-01

    Gluten promotes type 1 diabetes in nonobese diabetic (NOD) mice and likely also in humans. In NOD mice and in non-diabetes-prone mice, it induces inflammation in the pancreatic lymph nodes, suggesting that gluten can initiate inflammation locally. Further, gliadin fragments stimulate insulin secretion from beta cells directly. We hypothesized that gluten fragments may cross the intestinal barrier to be distributed to organs other than the gut. If present in pancreas, gliadin could interact directly with the immune system and the beta cells to initiate diabetes development. We orally and intravenously administered 33-mer and 19-mer gliadin peptide to NOD, BALB/c, and C57BL/6 mice and found that the peptides readily crossed the intestinal barrier in all strains. Several degradation products were found in the pancreas by mass spectroscopy. Notably, the exocrine pancreas incorporated large amounts of radioactive label shortly after administration of the peptides. The study demonstrates that, even in normal animals, large gliadin fragments can reach the pancreas. If applicable to humans, the increased gut permeability in prediabetes and type 1 diabetes patients could expose beta cells directly to gliadin fragments. Here they could initiate inflammation and induce beta cell stress and thus contribute to the development of type 1 diabetes. PMID:27795959

  5. An integrated cell purification and genomics strategy reveals multiple regulators of pancreas development.

    PubMed

    Benitez, Cecil M; Qu, Kun; Sugiyama, Takuya; Pauerstein, Philip T; Liu, Yinghua; Tsai, Jennifer; Gu, Xueying; Ghodasara, Amar; Arda, H Efsun; Zhang, Jiajing; Dekker, Joseph D; Tucker, Haley O; Chang, Howard Y; Kim, Seung K

    2014-10-01

    The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus.

  6. An Integrated Cell Purification and Genomics Strategy Reveals Multiple Regulators of Pancreas Development

    PubMed Central

    Benitez, Cecil M.; Qu, Kun; Sugiyama, Takuya; Pauerstein, Philip T.; Liu, Yinghua; Tsai, Jennifer; Gu, Xueying; Ghodasara, Amar; Arda, H. Efsun; Zhang, Jiajing; Dekker, Joseph D.; Tucker, Haley O.; Chang, Howard Y.; Kim, Seung K.

    2014-01-01

    The regulatory logic underlying global transcriptional programs controlling development of visceral organs like the pancreas remains undiscovered. Here, we profiled gene expression in 12 purified populations of fetal and adult pancreatic epithelial cells representing crucial progenitor cell subsets, and their endocrine or exocrine progeny. Using probabilistic models to decode the general programs organizing gene expression, we identified co-expressed gene sets in cell subsets that revealed patterns and processes governing progenitor cell development, lineage specification, and endocrine cell maturation. Purification of Neurog3 mutant cells and module network analysis linked established regulators such as Neurog3 to unrecognized gene targets and roles in pancreas development. Iterative module network analysis nominated and prioritized transcriptional regulators, including diabetes risk genes. Functional validation of a subset of candidate regulators with corresponding mutant mice revealed that the transcription factors Etv1, Prdm16, Runx1t1 and Bcl11a are essential for pancreas development. Our integrated approach provides a unique framework for identifying regulatory genes and functional gene sets underlying pancreas development and associated diseases such as diabetes mellitus. PMID:25330008

  7. Development of the pancreas in medaka, Oryzias latipes, from embryo to adult.

    PubMed

    Otsuka, Takayoshi; Tsukahara, Tatsuya; Takeda, Hiroyuki

    2015-10-01

    To address conserved and unique features of fish pancreas development, we performed extensive analyses of pancreatic development in medaka embryos and adults using pdx1- and ptf1a-transgenic medaka, in situ hybridization and immunohistochemistry. The markers used in these analyses included pdx1, nkx6.1, nkx6.2, nkx2.2, Islet1, insulin, Somatostatin, glucagon, ptf1a, ela3l, trypsin, and amylase. The double transgenic (Tg) fish produced in the present study visualizes the development of endocrine (pdx1+) and exocrine (ptf1a+) parts simultaneously in living fishes. Like other vertebrates, the medaka pancreas develops as two (dorsal and ventral) buds in the anterior gut tube, which soon fuse into a single anlagen. The double Tg fish demonstrates that the differential property between the two buds is already established at the initial phase of bud development as indicated by strong pdx1 expression in the dorsal one. This Tg fish also allowed us to examine the gross morphology and the structure of adult pancreas and revealed unique characters of medaka pancreas such as broad and multiple connections with the gut tube along the anterior-posterior axis. © 2015 Japanese Society of Developmental Biologists.

  8. Pancreatic Exocrine Insufficiency in Patients With Pancreatic or Periampullary Cancer: A Systematic Review.

    PubMed

    Tseng, Dorine S J; Molenaar, I Quintus; Besselink, Marc G; van Eijck, Casper H; Borel Rinkes, Inne H; van Santvoort, Hjalmar C

    2016-03-01

    The aim of this study was to determine the prevalence of pancreatic exocrine insufficiency in patients with pancreatic or periampullary cancer, both before and after resection. Systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA guidelines). We included studies reporting on pancreatic exocrine insufficiency in patients with pancreatic or periampullary cancer. Data on patient demographics, type of pancreatic resection, diagnostic test, and occurrence of pancreatic exocrine insufficiency were extracted. Prevalence of pancreatic exocrine insufficiency was calculated before and after pancreatic resections and in patients with locally advanced pancreatic cancer. Nine observational cohort studies with 693 patients were included. Median preoperative prevalence of pancreatic exocrine insufficiency was 44% (range, 42%-47%) before pancreatoduodenectomy, 20% (range, 16%-67%) before distal pancreatectomy, 63% before total pancreatectomy, and 25% to 50% in patients with locally advanced pancreatic cancer. The median prevalence of pancreatic exocrine insufficiency at least 6 months after pancreatoduodenectomy was 74% (range, 36%-100%) and 67% to 80% after distal pancreatectomy. Pancreatic exocrine insufficiency is diagnosed in approximately half of all patients scheduled to undergo resection for pancreatic or periampullary cancer. The prevalence increases markedly after resection. These data highlight the need of pancreatic enzyme suppletion in these patients.

  9. Human pancreas development.

    PubMed

    Jennings, Rachel E; Berry, Andrew A; Strutt, James P; Gerrard, David T; Hanley, Neil A

    2015-09-15

    A wealth of data and comprehensive reviews exist on pancreas development in mammals, primarily mice, and other vertebrates. By contrast, human pancreatic development has been less comprehensively reviewed. Here, we draw together those studies conducted directly in human embryonic and fetal tissue to provide an overview of what is known about human pancreatic development. We discuss the relevance of this work to manufacturing insulin-secreting β-cells from pluripotent stem cells and to different aspects of diabetes, especially permanent neonatal diabetes, and its underlying causes.

  10. Hydroalcohol extract of Trigonella foenum-graecum seed attenuates markers of inflammation and oxidative stress while improving exocrine function in diabetic rats.

    PubMed

    Joshi, Deval V; Patil, Rajesh R; Naik, Suresh R

    2015-02-01

    The herb fenugreek, Trigonella foenum-graecum Linn (Fabaceae), seeds have been traditionally used in the treatment of diabetes but its effect on oxidative stress and pro-inflammatory cytokines in the improvement of exocrine function of diabetes has not been studied. The effect of hydroalcoholic extract of Trigonella foenum-graecum seeds (HEF) on alloxan-induced type-II diabetic rat model was investigated. Effect of HEF (500, 1000, and 2000 mg/kg), glimepiride (4 mg/kg), and combination of HEF (500 mg/kg) + glimepiride (2 mg/kg), on alloxan-induced diabetic rats was evaluated by assaying (blood glucose, serum protein, glycosylated hemoglobin, muscle and liver glycogen, glucose uptake by diaphragm, liver glucose transport, serum pancreatic enzymes (α-amylase, lipase), pro-inflammatory cytokines (TNF-α, IL-6), antioxidant enzymes [glutathione (GSH), superoxide dismutase (SOD)], lipid peroxides (liver and pancreas), and histoarchitecture (liver, pancreas). Treatment with HEF (at different doses), glimepiride, and HEF + glimepiride increased body weight and glucose uptake, reduced plasma glucose, glycosylated hemoglobin, liver glucose transport, pro-inflammatory cytokines, pancreatic enzymes and restored depleted glycogen (muscle, liver) and total protein significantly (p < 0.01) and dose dependently, including prevention of lipid peroxidation and restoration of GSH and SOD (liver and pancreas). Treatment with HEF + glimepiride potentiated hypoglycemic activity of glimepiride. Histoarchitecture of liver and pancreas showed marked improvement. Present experimental findings suggest that HEF possesses promising hypoglycemic activity, presumably by amelioration of oxidative stress and pro-inflammatory cytokines. HEF may be useful as an adjuvant with clinically effective antidiabetic drugs in the management of type-II diabetes.

  11. Innocents on the Ice: A Memoir of Antarctic Exploration, 1957

    NASA Astrophysics Data System (ADS)

    Fitzgerald, Paul

    Many books have been written about Antarctica since early explorers first ventured inland from the coast in the early 20th century. Many of them have focused on the day-today rigors of staying alive and on the effort to survive by daring explorers who ventured where no person had been before. Innocents on Ice: A Memoir of Antarctic Exploration, 1957 by John Behrendt differs slightly by dealing not only with survival and exploration, but also with the day-to-day rigors of conducting scientific work in an inhospitable environment.Aside from the survival and the science, Behrendt's story also has a remarkable human side as he describes the battle between civilian scientists and an overbearing commanding naval officer with an unusual and controversial style of leadership. “Innocents” refers to the relative youth and inexperience of the traverse team of five young scientists who set out to explore and conduct geophysical and glaciological research in previously unexplored territory.

  12. Epidemiology of infections requiring hospitalization during long-term follow-up of pancreas transplantation.

    PubMed

    Rostambeigi, Nassir; Kudva, Yogish C; John, Seby; Mailankody, Sham; Pedersen, Rachel A; Dean, Patrick G; Prieto, Mikel; Cosio, Fernando G; Kremers, Walter K; Walker, Randall C; Abraham, Roshini S; Stegall, Mark D

    2010-05-15

    BACKGROUND.: Pancreas transplantation (PT) provides the best glycemic control option for diabetes mellitus but is associated with significant morbidities related to infectious disease. METHODS.: We performed a retrospective study of a cohort of consecutive PT recipients in whom PT was performed from 1998 to 2006 (n=216) and followed up them until July 2008. Data regarding infections, rejection, infection chemoprophylaxis, graft failure, absolute lymphocyte counts (ALCs), and mortalities were collected. RESULTS.: Simultaneous pancreas and kidney, pancreas transplantation alone, and pancreas after kidney (PAK) transplantations were performed in 42, 67, and 107 patients, with a mean (standard deviation) age at transplantation of 46.8 (8.03), 40.6 (10.1), and 43.7 (8.19) years. Of the simultaneous pancreas and kidney, pancreas transplantation alone, and PAK transplant recipients, 54.7%, 37.3%, and 58.8% were men. Overall, 63% developed a serious infection during the median follow-up of 6.4 years. Mean (range) number of infectious episodes was 2.3 (1-12), with mostly bacterial infections both within (68%) and after 1 year (78%). Incidence of bacterial and viral infections was greatest in the first 3 months after transplantation. Fungal infections were more constant. Bladder exocrine drainage was associated with higher risk of infection (hazard ratio=2.5, P<0.001). Infection within the first 3 months after transplantation was related to higher mortality after the first 3 months (hazard ratio=3.19). ALC was associated with the risk of first infections (P=0.005) and bacterial infections (P<0.001). CONCLUSIONS.: Incidence of infections after PT was 63% and mostly bacterial. Bladder drainage increases infection risk and low ALC partially predicts episodes. Limitations include retrospective design, unequal composition of PT groups, and lack of data between kidney and PT for PAK.

  13. Novel ciliate lipases for enzyme replacement during exocrine pancreatic insufficiency.

    PubMed

    Brock, Alexander; Aldag, Ingo; Edskes, Stella; Hartmann, Marcus; Herzog, Torsten; Uhl, Waldemar; Schnekenburger, Juergen

    2016-11-01

    Exocrine pancreatic insufficiency caused by inflammation or pancreatic tumors results in nutrient malfunction by a lack of digestive enzymes and neutralization compounds. Despite satisfactory clinical results with current enzyme therapies, a normalization of fat absorption in patients is rare. An individualized therapy is required that includes high dosage of enzymatic units, usage of enteric coating, and addition of gastric proton pump inhibitors. The key goal to improve this therapy is to identify digestive enzymes with high activity and stability in the gastrointestinal tract. We cloned and analyzed three novel ciliate lipases derived from Tetrahymena thermophila. Using highly precise pH-STAT-titration and colorimetric methods, we determined stability and lipolytic activity under physiological conditions in comparison with commercially available porcine and fungal digestive enzyme preparations. We measured from pH 2.0 to 9.0, with different bile salts concentrations, and substrates such as olive oil and fat derived from pig diet. Ciliate lipases CL-120, CL-130, and CL-230 showed activities up to 220-fold higher than Creon, pancreatin standard, and rizolipase Nortase within a pH range from pH 2.0 to 9.0. They are highly active in the presence of bile salts and complex pig diet substrate, and more stable after incubation in human gastric juice compared with porcine pancreatic lipase and rizolipase. The newly cloned and characterized lipases fulfilled all requirements for high activity under physiological conditions. These novel enzymes are therefore promising candidates for an improved enzyme replacement therapy for exocrine pancreatic insufficiency.

  14. Miracle of an Artificial Pancreas

    MedlinePlus

    ... diabetes, the realization of a successful, fully automated artificial pancreas is a dearly held dream. It signifies a life freer from nightly wake-up calls to check blood glucose or deliver insulin, a life freer from ... successful artificial pancreas would mark another huge step toward better ...

  15. 33 CFR 151.2015 - Is a vessel in innocent passage exempt from the mandatory requirements?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Ballast Water Management for Control of Nonindigenous Species in Waters of the United States § 151.2015 Is a vessel in innocent passage exempt from...

  16. Prox1-Heterozygosis Sensitizes the Pancreas to Oncogenic Kras-Induced Neoplastic Transformation12

    PubMed Central

    Drosos, Yiannis; Neale, Geoffrey; Ye, Jianming; Paul, Leena; Kuliyev, Emin; Maitra, Anirban; Means, Anna L; Washington, M Kay; Rehg, Jerold; Finkelstein, David B; Sosa-Pineda, Beatriz

    2016-01-01

    The current paradigm of pancreatic neoplastic transformation proposes an initial step whereby acinar cells convert into acinar-to-ductal metaplasias, followed by progression of these lesions into neoplasias under sustained oncogenic activity and inflammation. Understanding the molecular mechanisms driving these processes is crucial to the early diagnostic and prevention of pancreatic cancer. Emerging evidence indicates that transcription factors that control exocrine pancreatic development could have either, protective or facilitating roles in the formation of preneoplasias and neoplasias in the pancreas. We previously identified that the homeodomain transcription factor Prox1 is a novel regulator of mouse exocrine pancreas development. Here we investigated whether Prox1 function participates in early neoplastic transformation using in vivo, in vitro and in silico approaches. We found that Prox1 expression is transiently re-activated in acinar cells undergoing dedifferentiation and acinar-to-ductal metaplastic conversion. In contrast, Prox1 expression is largely absent in neoplasias and tumors in the pancreas of mice and humans. We also uncovered that Prox1-heterozygosis markedly increases the formation of acinar-to-ductal-metaplasias and early neoplasias, and enhances features associated with inflammation, in mouse pancreatic tissues expressing oncogenic Kras. Furthermore, we discovered that Prox1-heterozygosis increases tissue damage and delays recovery from inflammation in pancreata of mice injected with caerulein. These results are the first demonstration that Prox1 activity protects pancreatic cells from acute tissue damage and early neoplastic transformation. Additional data in our study indicate that this novel role of Prox1 involves suppression of pathways associated with inflammatory responses and cell invasiveness. PMID:26992918

  17. Cytosolic Ca2+ and Ca2+-activated Cl− current dynamics: insights from two functionally distinct mouse exocrine cells

    PubMed Central

    Giovannucci, David R; Bruce, Jason I. E; Straub, Stephen V; Arreola, Jorge; Sneyd, James; Shuttleworth, Trevor J; Yule, David I

    2002-01-01

    The dynamics of Ca2+ release and Ca2+-activated Cl− currents in two related, but functionally distinct exocrine cells, were studied to gain insight into how the molecular specialization of Ca2+ signalling machinery are utilized to produce different physiological endpoints: in this case, fluid or exocytotic secretion. Digital imaging and patch-clamp methods were used to monitor the temporal and spatial properties of changes in cytosolic Ca2+ concentration ([Ca2+]c) and Cl− currents following the controlled photolytic release of caged-InsP3 or caged-Ca2+. In parotid and pancreatic acinar cells, changes in [Ca2+]c and activation of a Ca2+-activated Cl− current occurred with close temporal coincidence. In parotid, a rapid global Ca2+ signal was invariably induced, even with low-level photolytic release of threshold amounts of InsP3. In pancreas, threshold stimulation generated an apically delimited [Ca2+]c signal, while a stronger stimulus induced a global [Ca2+]c signal which exhibited characteristics of a propagating wave. InsP3 was more effective in parotid, where [Ca2+]c signals initiated with shorter latency and exhibited a faster time-to-peak than in pancreas. The increased potency of InsP3 in parotid probably results from a four-fold higher number of InsP3 receptors as measured by radiolabelled InsP3 binding and western blot analysis. The Ca2+ sensitivity of the Cl− channels in parotid and pancreas was determined from the [Ca2+]-current relationship measured during a dynamic ‘Ca2+ ramp’ produced by the continuous, low-level photolysis of caged-Ca2+. In addition to a greater number of InsP3 receptors, the Cl− current density of parotid acinar cells was more than four-fold greater than that of pancreatic cells. Whereas activation of the current was tightly coupled to increases in Ca2+ in both cell types, local Ca2+ clearance was found to contribute substantially to the deactivation of the current in parotid. These data reveal specializations of

  18. Surgery for pancreas divisum.

    PubMed Central

    Varshney, Subodh; Johnson, Colin D.

    2002-01-01

    We present our experience of open surgical treatment in 5 patients with symptomatic pancreas divisum (PD). Choice of therapy was based on allocation of patients to one of five clinical presentation groups: (i) with minor symptoms (no operation); (ii) with recurrent acute pancreatitis or upper abdominal pain (RAP/RUAP)--3 patients; (iii) with radiological evidence of chronic pancreatitis (CP)--1 patient; (iv) chronic pancreatic pain without radiological evidence of chronic pancreatitis (CPP); and (v) other pancreatic complications--1 patient. This classification helps to decide management and predict possible outcome. Various types of operation were performed as indicated (open surgical accessory sphincteroplasty [2 also had distal pancreatectomy], n = 3; Puestow's operation, n = 1; or Beger's pancreatectomy, n = 1). All patients improved significantly and are now leading normal personal, professional, and social lives. We conclude that, with careful selection of patients and appropriate therapy, the response to surgical treatment is good. PMID:12092866

  19. Juvenile Diabetes Mellitus and Concurrent Exocrine Pancreatic Insufficiency in a Labrador Retriever: Long-Term Management.

    PubMed

    Alvarez, Maria Saiz; Herrería-Bustillo, Vicente; Utset, Artur Font; Martínez, Jorge

    2015-01-01

    A 3 mo old, female, entire Labrador retriever presented with vomiting, diarrhea, polyuria, polydipsia, polyphagia, and stunted growth. Diagnostics revealed the presence of juvenile diabetes mellitus and concurrent exocrine pancreatic insufficiency. Pancreatic histopathology showed severe pancreatic atrophy. Successful treatment was achieved with a combination of insulin and pancreatic enzymes. This report describes successful long-term treatment of juvenile diabetes mellitus and concurrent exocrine pancreatic insufficiency in a dog.

  20. Current knowledge on exocrine glands in carabid beetles: structure, function and chemical compounds.

    PubMed

    Giglio, Anita; Brandmayr, Pietro; Talarico, Federica; Brandmayr, Tullia Zetto

    2011-01-01

    Many exocrine products used by ground beetles are pheromones and allomones that regulate intra- and interspecific interactions and contribute to their success in terrestrial ecosystems. This mini-review attempts to unify major themes related to the exocrine glands of carabid beetles. Here we report on both glandular structures and the role of secretions in carabid adults, and that little information is available on the ecological significance of glandular secretions in pre-imaginal stages.

  1. Non-invasive discrimination between pancreatic islets and exocrine cells using multiphoton microscopy

    NASA Astrophysics Data System (ADS)

    Wu, Binlin; Li, Ge; Hao, Mingming; Mukherjee, Sushmita

    2015-03-01

    In this study, we propose a non-invasive method to distinguish pancreatic islet cells from exocrine cell clusters using multiphoton (MP) imaging. We demonstrate the principle of distinguishing them based on autofluorescence. The results show that MP imaging has a potential to distinguish pancreatic islets from exocrine cells. This ability to distinguish the two cell types could have many applications, such as the examination of fresh pancreatic biopsies when staining is not possible or desirable.

  2. Current knowledge on exocrine glands in carabid beetles: structure, function and chemical compounds

    PubMed Central

    Giglio, Anita; Brandmayr, Pietro; Talarico, Federica; Brandmayr, Tullia Zetto

    2011-01-01

    Abstract Many exocrine products used by ground beetles are pheromones and allomones that regulate intra- and interspecific interactions and contribute to their success in terrestrial ecosystems. This mini-review attempts to unify major themes related to the exocrine glands of carabid beetles. Here we report on both glandular structures and the role of secretions in carabid adults, and that little information is available on the ecological significance of glandular secretions in pre-imaginal stages. PMID:21738412

  3. Fluconazole Penetration into the Pancreas

    PubMed Central

    Shrikhande, Shailesh; Friess, Helmut; Issenegger, Claudia; Martignoni, Marcus E.; Yong, Huang; Gloor, Beat; Yeates, Rodney; Kleeff, Jörg; Büchler, Markus W.

    2000-01-01

    Because of antibiotic prophylaxis for necrotizing pancreatitis, the frequency of fungal superinfection in patients with pancreatic necrosis is increasing. In this study we analyzed the penetration of fluconazole into the human pancreas and in experimental acute pancreatitis. In human pancreatic tissues, the mean fluconazole concentration was 8.19 ± 3.38 μg/g (96% of the corresponding concentration in serum). In experimental edematous and necrotizing pancreatitis, 88 and 91% of the serum fluconazole concentration was found in the pancreas. These data show that fluconazole penetration into the pancreas is sufficient to prevent and/or treat fungal contamination in patients with pancreatic necrosis. PMID:10952621

  4. Low fecal elastase 1 levels do not indicate exocrine pancreatic insufficiency in type-1 diabetes mellitus.

    PubMed

    Hahn, Jan-Uwe; Kerner, Wolfgang; Maisonneuve, Patrick; Lowenfels, Albert B; Lankisch, Paul Georg

    2008-04-01

    On the basis of very low fecal elastase 1 and very high fecal fat estimations, it has been claimed that exocrine pancreatic insufficiency is frequent in diabetic patients, and that in up to 40% of the patients, pancreatic enzyme substitution would be indicated. Because this would affect millions of diabetic patients worldwide, we evaluated this suggestion by testing exocrine pancreatic function in type-1 diabetes using the criterion standard of exocrine pancreatic function tests, the secretin-cerulein test (SCT). The results of this test were then compared with those of fecal elastase 1 and fecal fat estimations. Thirty-three patients with type-1 diabetes mellitus underwent an SCT, a fecal fat estimation, and 2 fecal elastase 1 tests (using both monoclonal and polyclonal antibodies) to evaluate their exocrine pancreatic function. The SCT results were abnormal in 11 of the 33 patients, who showed only mild to moderate exocrine pancreatic insufficiency, and the stimulated lipase secretion was never less than 10% of the level where pancreatic steatorrhea first occurs. The correlation between fecal elastase 1 and SCT showed much lower sensitivity, specificity, and positive and negative predictive values than did the correlation between SCT and fecal fat. Nonpancreatogenic steatorrhea was present in two thirds of the patients and was probably caused by bacterial overgrowth. Neither low fecal elastase 1 nor raised fecal fat levels reliably indicate exocrine pancreatic insufficiency in type-1 diabetes and therefore should not be used as an indicator for expensive pancreatic enzyme substitution.

  5. A possible role for guanosine 3',5'-monophosphate in the stimulus-secretion coupling in exocrine pancreas.

    PubMed

    Kapoor, C L; Krishna, G

    1978-11-15

    Carbamylcholine, caerulein and cholecystokinin octapeptide rapidly increased the cyclic GMP concentration and amylase secretion in isolated guinea pig pancreatic slices. The cyclic GMP concentration was increased eight-fold over the basal concentration in 30 s, with concomitant increase in the rate of amylase secretion. The tissue concentration of cyclic GMP then rapidly declined to a plateau value of approx. 16% of the peak level within 10 min and was maintained at that concentration for the duration of the experiment. We have shown earlier (Kapoor, CL. and Krishna, G. (1977) Science 196, 1003--1005) that the decrease of tissue cyclic GMP was due mainly to the secretion of cyclic GMP into the medium. The cyclic AMP concentration in the tissue was not changed, nor was it secreted into the medium. There was a correlation between the concentration response to various agents for the increase in cyclic GMP concentration and amylase secretion in pancreatic slices. Carbamylcholine increased both the cyclic GMP concentration and amylase secretion; the half-maximal effect was achieved at 1.5 micrometer concentration. Caerulein and cholecystokinin octapeptide were 5000 times more potent than carbamylcholine in increasing cyclic GMP concentration and amylase secretion; the half-maximal effect was achieved at 0.3 nM concentration. Atropine, which completely inhibited the increase in cyclic GMP and amylase secretion induced by carbamylcholine, did not block the effects of caerulein or cholecystokinin octapeptide. These results suggest that various secretagogues induced amylase secretion by increasing the cyclic GMP concentration, but the mechanism by which cyclic GMP caused amylase secretion remains to be elucidated.

  6. Hydrogen Sulfide Regulates Ca2+ Homeostasis Mediated by Concomitantly Produced Nitric Oxide via a Novel Synergistic Pathway in Exocrine Pancreas

    PubMed Central

    Moustafa, Amira

    2014-01-01

    Abstract Aim: The present study was designed to explore the effects of hydrogen sulfide (H2S) on Ca2+ homeostasis in rat pancreatic acini. Results: Sodium hydrosulfide (NaHS; an H2S donor) induced a biphasic increase in the intracellular Ca2+ concentration ([Ca2+]i) in a dose-dependent manner. The NaHS-induced [Ca2+]i elevation persisted with an EC50 of 73.3 μM in the absence of extracellular Ca2+ but was abolished by thapsigargin, indicating that both Ca2+ entry and Ca2+ release contributed to the increase. The [Ca2+]i increase was markedly inhibited in the presence of NG-monomethyl L-arginine or 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), and diaminofluorescein-2/diaminofluorescein-2 triazole (DAF-2/DAF-2T) fluorometry demonstrated that nitric oxide (NO) was also produced by H2S in a dose-dependent manner with an EC50 of 64.8 μM, indicating that NO was involved in the H2S effect. The H2S-induced [Ca2+]i increase was inhibited by pretreatment with U73122, xestospongin C, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, KT5823, and GP2A, indicating that phospholipase C (PLC), the inositol 1,4,5-trisphosphate (IP3) receptor, soluble guanylate cyclase (sGC), protein kinase G (PKG), and Gq-protein play roles as intermediate components in the H2S-triggered intracellular signaling. Innovation: To our knowledge, our study is the first one highlighting the effect of H2S on intracellular Ca2+ dynamics in pancreatic acinar cells. Moreover, a novel cascade was presumed to function via the synergistic interaction between H2S and NO. Conclusion: We conclude that H2S affects [Ca2+]i homeostasis that is mediated by H2S-evoked NO production via an endothelial nitric oxide synthase (eNOS)-NO-sGC-cyclic guanosine monophosphate-PKG-Gq-protein-PLC-IP3 pathway to induce Ca2+ release, and this pathway is identical to the one we recently proposed for a sole effect of NO and the two gaseous molecules synergistically function to regulate Ca2+ homeostasis. Antioxid. Redox Signal. 20, 747–758. PMID:24138560

  7. SYNTHESIS AND MIGRATION OF PROTEINS IN THE CELLS OF THE EXOCRINE PANCREAS AS REVEALED BY SPECIFIC ACTIVITY DETERMINATION FROM RADIOAUTOGRAPHS

    PubMed Central

    Warshawsky, H.; Leblond, C. P.; Droz, B.

    1963-01-01

    Radioautographs of pancreatic acinar cells were prepared in rats and mice sacrificed at various times after injection of leucine-, glycine-, or methionine-H3. Measurements of radioactivity concentration (number of silver grains per unit area) and relative protein concentration (by microspectrophotometry of Millon-treated sections) yielded the mean specific activity of proteins in various regions of the acinar cells. The 2 to 5 minute radioautographs as well as the specific activity time curves demonstrate protein synthesis in ergastoplasm. From there, most newly synthesized proteins migrate to and accumulate in the Golgi zone. Then they spread to the whole zymogen region and, finally, enter the excretory ducts. An attempt at estimating turnover times indicated that two classes of proteins are synthesized in the ergastoplasm: "sedentary" with a slow turnover (62.5 hours) and "exportable" with rapid turnover (4.7 minutes). It is estimated that the exportable proteins spend approximately 11.7 minutes in the Golgi zone where they are built up into zymogen granules, and thereafter 36.0 minutes as fully formed zymogen granules, before they are released outside the acinar cell as pancreatic secretion. The mean life span of a zymogen granule in the cell is estimated to be 47.7 minutes. PMID:13999005

  8. [A brief history of the anatomy and physiology of a mysterious and hidden gland called the pancreas].

    PubMed

    Navarro, Salvador

    2014-11-01

    Because of its retrogastric location and appearance, which is similar to mesenteric fat, for centuries the pancreas has been a mysterious, hidden organ that has received little attention. However, its importance was intuited and described by Herophilus, Ruphos of Ephesus and Galen. This gland began to appearin distinct medical treatises from the 16th century. There are two important scientists in the history of the pancreas. The fist, Johann Georg Wirsung, described the main pancreatic duct in 1642, a date considered by many to be the start of Pancreatology. The second, Claude Bernard, described pancreatic exocrine function between 1849 and 1856 and is considered the father of pancreatic physiology. Besides these two outstanding figures, there is a constellation of personalities who contributed to improving knowledge of this enigmatic gland with the results of their studies. The aim of this article is to call attention to some of the most notable findings that have enhanced knowledge of this gland over the years.

  9. [Laparoscopic distal resection of the pancreas].

    PubMed

    Gürlich, R; Sixta, B; Oliverius, M; Kment, M; Rusina, R; Spicák, J; Sváb, J

    2005-09-01

    During the last two years, reports on laparoscopic procedures of the pancreas have been on increase. Laparoscopic resection of the pancreatic cauda is indicated, primarily, for benign cystic lesions of the cauda of the pancreas and for neuroendocrine tumors of the pancreas (mainly insulinomas). We have not recorded any report on the above procedure in the Czech literature. Therefore, in our case review, we have described laparoscopic distal resection of the pancreas with splenectomy for a pseudopapillary tumor of the pancreas.

  10. Common Disorders of the Pancreas

    MedlinePlus

    ... States is chronic alcohol consumption. Additional causes include cystic fibrosis and other hereditary disorders ofthe pancreas. For a ... inherited disorder that leads to chronic pancreatitis is cystic fibrosis. Recent research demonstrates genetic testing can be a ...

  11. Generating new pancreas from old.

    PubMed

    Hardikar, Anandwardhan A

    2004-07-01

    Pancreas regeneration after tissue damage is a key response to pancreatic injury, involving pancreatic duct progenitor cells and intra-islet precursor cells. Surgical removal of the pancreas, duct obstruction by cellophane wrapping and bone marrow-derived stem cell transplantation act as inductive stimuli, leading to pancreas regeneration. The exact role of growth and differentiation factors regulating pancreatic beta-cell mass remains unknown. Here, I will attempt to integrate recent findings and speculate on the factors that trigger this fascinating response, wherein the pancreas responds to a deficit in cell mass and undergoes new islet formation, leading to restoration of normal beta-cell mass. I will also discuss recent advances in regenerating endocrine pancreatic cells, which could affect stem cell-based approaches to treating diabetes mellitus.

  12. Membrane interactions between secretion granules and plasmalemma in three exocrine glands

    PubMed Central

    Tanaka, Y; De Camilli, P; Meldolesi, J

    1980-01-01

    Three types of membrane interactions were studied in three exocrine systems (the acinar cells of the rat parotid, rat lacrimal gland, and guinea pig pancrease) by freeze- fracture and thin-section electron microscopy: exocytosis, induced in vivo by specific pharmacological stimulations; the mutual apposition of secretory granule membranes in the intact cell; membrane appositions induced in vitro by centrifugation of the isolated granules. In all three glandular cells, the distribution of intramembrane particles (IMP) on the fracture faces of the luminal plasmagranule membrane particles (IMP) on the fracture faces of the lumenal plasmalemma appeared random before stimulation. However, after injection of secretagogues, IMP were rapidly clearly from the areas of granule- plasmalemma apposition in the parotid cells and, especially, in lacrimocytes. In the latter, the cleared areas appeared as large bulges toward the lumen, whereas in the parotid they were less pronounced. Exocytotic openings were usually large and the fracture faces of their rims were covered with IMP. In contrast, in stimulated pancreatic acinar cells, the IMP distribution remained apparently random after stimulation. Exocytoses were established through the formation of narrown necks, and no images which might correspond to early stages of membrane fusion were revealed. Within the cytoplasm of parotid and lacrimal cells (but not in the pancreas), both at rest and after stimulation, secretion granules were often closely apposed by means of flat, circular areas, also devoid of IMP. In thin sections, the images corresponding to IMP-free areas were close granule-granule and granule-plasmalemma appositions, sometimes with focal merging of the membrane outer layers to yield pentalaminar structures. Isolated secretion granules were forced together in vitro by centrifugation. Under these conditions, increasing the centrifugal force from 1,600 to 50,000 g for 10 min resulted in a progressive, statistically

  13. Innocent Bystanders and Smoking Guns: Dwarf Carbon Stars

    NASA Astrophysics Data System (ADS)

    Green, Paul J.

    2014-01-01

    As far as we know, most carbon throughout the Universe is created and dispersed by AGB stars. So it was at first surprising to find that the carbon stars most prevalent in the Galaxy are in fact dwarfs. We suspect that dC stars are most likely innocent bystanders in post-mass transfer binaries, and may be predominantly metal-poor. Among 1200 C stars found in the SDSS (Green 2013), we confirm 724 dCs, of which a dozen are DA/dC stars in composite spectrum binaries, quadrupling the total sample of these "smoking guns" for AGB binary mass transfer. The dCs likely span absolute magnitudes M_i from about 6.5 to 10.5. G-type dC stars with weak CN and relatively blue colors are probably the most massive dCs still cool enough to show C_2 bands. Eleven very red C stars with strong red CN bands appear to be N-type AGB stars at large Galactocentric distances, one likely a new discovery in the dIrr galaxy Le A. Two such stars within 30arcmin of each other may trace a previously unidentified dwarf galaxy or tidal stream at ~40 kpc. We describe follow-up projects to study the spatial, kinematic, and binary properties of these C-enriched dwarfs.

  14. Hyponatremia in hepatic encephalopathy: an accomplice or innocent bystander?

    PubMed

    Yun, Byung Cheol; Kim, W Ray

    2009-06-01

    Hyponatremia, a common complication inpatients with advanced liver disease and impaired free water clearance, has been shown to be an important predictor of short-term mortality. Hepatic encephalopathy, also a late complication of end-stage liver disease, has been associated with low-grade cerebral edema as a result of swelling of astrocytes. Guevara et al. hypothesized that hyponatremia and the resultant depletion of organic osmolytes (e.g.,myo-inositol) from brain cells contribute to brain edema, playing an important role in the pathogenesis of hepatic encephalopathy. Using a multivariable analysis, they demonstrated that hyponatremia increased the risk of hepatic encephalopathy more than eightfold, after adjustment for serum bilirubin and creatinine concentrations and previous history of encephalopathy. Their magnetic resonance spectroscopy data correlated low brain concentrations of myoinositol with hepatic encephalopathy. As both hyponatremia and encephalopathy occur in patients with advanced liver disease, it has been difficult to implicate hyponatremia independently in the pathogenesis of hepatic encephalopathy. Guevara's data do suggest that hyponatremia is more likely an accomplice than an innocent bystander.

  15. Current status of pancreas transplantation.

    PubMed Central

    Cook, D W; Sasaki, T

    1989-01-01

    Pancreas transplantation for the treatment of diabetes mellitus is being done with increasing frequency. Refined operative techniques, an improved immunosuppression regimen, and an earlier recognition of rejection have led to dramatic increases in both graft and patient survival rates. Preliminary data suggest that a functioning pancreatic allograft may arrest or reverse most of the complications of diabetes, although the effects on retinopathy remain controversial. Patients also acquire a strong sense of well-being after successful pancreas transplantation. PMID:2660412

  16. Pancreas Transplantation From Living Donors: A Single Center Experience of 20 Cases.

    PubMed

    Choi, J Y; Jung, J H; Kwon, H; Shin, S; Kim, Y H; Han, D J

    2016-08-01

    Living donor pancreas transplantation (LDPT) has several advantages over deceased donor pancreas transplantation (DDPT), including better HLA matching, shorter ischemic time, and shorter waiting time. It remains an attractive option for diabetes mellitus (DM) patients with end stage renal disease. We reviewed 20 cases of LDPT performed in Asan Medical Center between October 1992 and March 2015. Six cases (30%) were pancreas transplantation alone (PTA), and the rest (70%) were simultaneous pancreas and kidney transplantation (SPK). Relations of donor and recipient were parents in 7 (35%), siblings in 6 (30%), spouse in 6 (30%), and cousin in 1 (5%). Graft survival in SPK at 1, 3, 5, and 10 years was 91.7%, 83.3%, 83.3%, and 83.3%, respectively, and that in PTA recipients was 50%, 33.3%, 16.7%, and 16.7%, respectively (p = 0.005). Causes of graft failure in SPK were thrombosis (one case), and rejection (one case), whereas those in PTA were noncompliance (two cases), thrombosis (one case), reflux pancreatitis (one case), and chronic rejection (one case). In terms of pancreas exocrine drainage, two grafts (25%) maintained their function in bladder drainage, while all grafts maintained in enteric drainage p < 0.05). Seven (35%) donors experienced minor pancreatic juice leakage and one underwent reoperation due to postoperative hematoma. Most donors maintained normoglycemia and normal renal function. However, two donors developed DM (at 1 and 90 months postdonation), and were treated with oral hypoglycemic agents. Graft survival in PTA recipients was poorer than in SPK due to poor compliance and bladder drainage-related problems. The surgical and metabolic complication rates of donors can be minimized by applying strict donor criteria. Therefore, LDPT with enteric drainage is an acceptable treatment for SPK. © Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.

  17. Ethanol diversely alters palmitate, stearate and oleate metabolism in the liver and pancreas of rats using the deuterium oxide single tracer

    PubMed Central

    Boros, Laszlo G.; Deng, Qinggao; Pandol, Stephen J.; Tsukamoto, Hidekazu; Go, Vay Liang W.; Lee, Wai-Nang Paul

    2015-01-01

    Objective To determine tissue specific effects of alcohol on fatty acid synthesis and distribution as related to functional changes in triglyceride transport and membrane formation. Methods Tissue fatty acid profile, and de novo lipogenesis were determined in adult male Wistar rats after 5 weeks of ethanol feeding using deuterated water and GC/MS. Liver and pancreas fatty acid profiles and new synthesis fractions were compared with those from control rats on an isocaloric diet. Results Fatty acid ratios in the liver indicated that there was an over two-fold accumulation of stearate to that of palmitate, with an apparent decrease in oleate content. On the other hand, in the pancreas there was a 17% decrease in the stearate to palmitate ratio, while oleate to palmitate ratio was increased by 30%. The fractions of deuterium labeled palmitate and stearate were substantially reduced in the liver and pancreas of the alcohol treated animals. Deuterium labeling of oleate was reduced in the liver but not in the pancreas consistent with the oleate/stearate ratios in these tissues. Conclusions Long-term alcohol exposure results in opposite effects on the desaturase activity in the liver and pancreas limiting fatty acid transport in the liver but promoting the exocrine function of the pancreas. PMID:19248221

  18. Ethanol diversely alters palmitate, stearate, and oleate metabolism in the liver and pancreas of rats using the deuterium oxide single tracer.

    PubMed

    Boros, Laszlo G; Deng, Qinggao; Pandol, Stephen J; Tsukamoto, Hidekazu; Go, Vay Liang W; Lee, Wai-Nang Paul

    2009-03-01

    To determine tissue-specific effects of alcohol on fatty acid synthesis and distribution as related to functional changes in triglyceride transport and membrane formation. Tissue fatty acid profile and de novo lipogenesis were determined in adult male Wistar rats after 5 weeks of ethanol feeding using deuterated water and gas chromatography/mass spectrometry. Liver and pancreas fatty acid profiles and new synthesis fractions were compared with those from control rats on an isocaloric diet. Fatty acid ratios in the liver indicated that there was a more than 2-fold accumulation of stearate to that of palmitate, with an apparent decrease in oleate content. On the other hand, in the pancreas, there was a 17% decrease in the stearate-to-palmitate ratio, whereas the oleate-to-palmitate ratio was increased by 30%. The fractions of deuterium-labeled palmitate and stearate were substantially reduced in the liver and pancreas of the alcohol-treated animals. Deuterium labeling of oleate was reduced in the liver but not in the pancreas, consistent with the oleate/stearate ratios in these tissues. Long-term alcohol exposure results in opposite effects on the desaturase activity in the liver and pancreas, limiting fatty acid transport in the liver but promoting the exocrine function of the pancreas.

  19. Immunohistochemistry Detected and Localized Cannabinoid Receptor Type 2 in Bovine Fetal Pancreas at Late Gestation

    PubMed Central

    Dall’Aglio, Cecilia; Polisca, Angela; Cappai, Maria Grazia; Mercati, Francesca; Troisi, Alessandro; Pirino, Carolina; Scocco, Paola; Maranesi, Margherita

    2017-01-01

    At present, data on the endocannabinoid system expression and distribution in the pancreatic gland appear scarce and controversial as descriptions are limited to humans and laboratory animals. Since the bovine pancreas is very similar to the human in endocrine portion development and control, studies on the fetal gland could prove to be very interesting, as an abnormal maternal condition during late pregnancy may be a predisposing trigger for adult metabolic disorders. The present investigation studied cannabinoid receptor type 2 presence and distribution in the bovine fetal pancreas towards the end of gestation. Histological analyses revealed numerous endocrinal cell clusters or islets which were distributed among exocrine adenomeri in connectival tissue. Immunohistochemistry showed that endocrine-islets contained some CB2-positive cells with a very peculiar localization that is a few primarily localized at the edges of islets and some of them also scattered in the center of the cluster. Characteristically, also the epithelium of the excretory ducts and the smooth muscle layers of the smaller arteries, in the interlobular glandular septa, tested positive for the CB2 endocannabinoid receptor. Consequently, the endocannabinoid system, via the cannabinoid receptor type 2, was hypothesized to play a major role in controlling pancreas function from normal fetal development to correct metabolic functioning in adulthood. PMID:28348424

  20. Crosstalk between the developing pancreas and its blood vessels: an evolving dialogue

    PubMed Central

    Villasenor, Alethia; Cleaver, Ondine

    2015-01-01

    Growth and development of embryonic organs goes hand in hand with development of the vascular system. Blood vessels have been known for centuries to supply nutrients and oxygen to all cell types in an organism, however, they have more recently been shown to provide specific cues required for the formation and functionality of a number of tissues. Here, we review the role of blood vessels during pancreas formation, from early specification of the initial pancreatic bud, to its growth and maturation. The overarching theme that emerges from the many studies carried out in the past decade is that the vasculature likely plays diverse and changing roles during pancreas organogenesis. Blood vessels are required for endocrine specification at the onset of pancreatic budding, while only a few days later, blood vessels suppress pancreatic branching and exocrine differentiation. In this review, we summarize our understanding to date about the crosstalk between the pancreas and its vasculature, and we provide a perspective on the promises and challenges of the field. PMID:22728668

  1. Crosstalk between the developing pancreas and its blood vessels: an evolving dialog.

    PubMed

    Villasenor, Alethia; Cleaver, Ondine

    2012-08-01

    Growth and development of embryonic organs goes hand in hand with development of the vascular system. Blood vessels have been known for centuries to supply nutrients and oxygen to all cell types in an organism, however, they have more recently been shown to provide specific cues required for the formation and functionality of a number of tissues. Here, we review the role of blood vessels during pancreas formation, from early specification of the initial pancreatic bud, to its growth and maturation. The overarching theme that emerges from the many studies carried out in the past decade is that the vasculature likely plays diverse and changing roles during pancreas organogenesis. Blood vessels are required for endocrine specification at the onset of pancreatic budding, while only a few days later, blood vessels suppress pancreatic branching and exocrine differentiation. In this review, we summarize our understanding to date about the crosstalk between the pancreas and its vasculature, and we provide a perspective on the promises and challenges of the field. Copyright © 2012. Published by Elsevier Ltd.

  2. Distinct phenotype and function of NK cells in the pancreas of nonobese diabetic mice.

    PubMed

    Brauner, Hanna; Elemans, Marjet; Lemos, Sara; Broberger, Christian; Holmberg, Dan; Flodström-Tullberg, Malin; Kärre, Klas; Höglund, Petter

    2010-03-01

    Little is known about target organ-infiltrating NK cells in type 1 diabetes and other autoimmune diseases. In this study, we identified NK cells with a unique phenotype in the pancreas of NOD mice. Pancreatic NK cells, localized to the endocrine and exocrine parts, were present before T cells during disease development and did not require T cells for their infiltration. Furthermore, NK cells, or NK cell precursors, from the spleen could traffic to the pancreas, where they displayed the pancreatic phenotype. Pancreatic NK cells from other mouse strains shared phenotypic characteristics with pancreatic NK cells from NOD mice, but displayed less surface killer cell lectin-like receptor G1, a marker for mature NK cells that have undergone proliferation, and also did not proliferate to the same extent. A subset of NOD mouse pancreatic NK cells produced IFN-gamma spontaneously, suggesting ongoing effector responses. However, most NOD mouse pancreatic NK cells were hyporesponsive compared with spleen NK cells, as reflected by diminished cytokine secretion and a lower capacity to degranulate. Interestingly, such hyporesponsiveness was not seen in pancreatic NK cells from the nonautoimmune strain C57BL/6, suggesting that this feature is not a general property of pancreatic NK cells. Based on our data, we propose that NK cells are sentinel cells in a normal pancreas. We further speculate that during inflammation, pancreatic NK cells initially mediate proinflammatory effector functions, potentially contributing to organ-specific autoimmunity, but later become hyporesponsive because of exhaustion or regulation.

  3. Intraductal tubulopapillary neoplasm of the pancreas on fine needle aspiration: case report with differential diagnosis.

    PubMed

    Guan, Hui; Gurda, Grzegorz; Lennon, Anne Marie; Hruban, Ralph H; Erozan, Yener S

    2014-02-01

    Intraductal tubulopapillary neoplasm (ITPN) is a rare primary pancreatic neoplasm accounting for less than 1% of all pancreatic exocrine neoplasms and 3% of intraductal neoplasms of the pancreas. Data on this entity are still limited. Here, we report a case of ITPN with cytopathologic and histopathologic findings. A 41-year-old woman with a 2.2 cm cyst in the head of the pancreas for five years was referred to our institution. The endoscopic ultrasound-guided fine-needle aspiration produced cytospins were moderately cellular with a few fragments of markedly atypical epithelium. The neoplastic cells displayed high-grade nuclear atypia with enlarged, eccentric nuclei, anisonucleosis and prominent nucleoli, irregular nuclear membranes, high nucleus to cytoplasmic (N/C) ratios, and a moderate amount of cytoplasm with no intracytoplasmic mucin. Histologically, the lesion was found to be an ITPN with focal high-grade dysplasia. No invasive carcinoma was identified. The neoplastic cells exhibited luminal immunolabeling for MUC-1, but were negative for MUC-2, trypsin, chymotrypsin, and P53. Approximately 5% of the neoplastic cells showed Ki-67 immunoreactivity. ITPN of pancreas may be a source of markedly atypical epithelial cells in pancreatic cystic aspiration. Clinical and radiographic findings, molecular mutational analysis, in combination with cytological features are essential to differentiate it from other disease entities.

  4. Ganglionar nervous cells and telocytes in the pancreas of Octodon degus: extra and intrapancreatic ganglionar cells and telocytes in the degus.

    PubMed

    Bosco, Cleofina; Díaz, Eugenia; Gutiérrez, Rodrigo; González, Jaime; Pérez, Johanna

    2013-10-01

    This study shows for the first time the presence of intra and extrapancreatic ganglionar neurons and telocytes in Octodon degus such as those described in human and guinea pig pancreas. Pancreatic ganglionar neurons were identified by their histological characteristics as well as their positive immunostaining with mouse anti-human neuron specific enolase (NSE) antibody. Somatostatin secreting delta cells (D cells) in the islets of Langerhans were identified by positive immunostaining with rabbit antihuman polyclonal somatostatin antibody. Electron microscopy evidenced the presence of some unmyelinated axons in the interlobular spaces or septa, usually located adjacent to blood vessels and the exocrine epithelial ducts. The presence of telocytes with at least 2 telopodes was observed in the interlobular space, frequently in close spatial relationship with blood vessels and nerve endings. Telocytes were often observed in the vicinity or even in close proximity with both secretory acini and exocrine epithelial ducts and regulatory nerves and blood vessel apparatuses. A possible framework has been put forward within which such structures might contribute to elicit physiological responses in the pancreas. Further studies of synaptic interactions within and between pancreatic neuron cells are needed to help clarify the morphological results reported here. A broad overview of the field of neurogastroenterology with focus on the pancreas of O. degus related to the enteric nervous system (ENS) is provided in order to help design future studies on the connections of specific neurons forming pancreatic pathways, their neurotransmission processes and how disruption of these pathways may contribute to pancreatic disease.

  5. Leucine markedly regulates pancreatic exocrine secretion in goats.

    PubMed

    Yu, Z P; Xu, M; Liu, K; Yao, J H; Yu, H X; Wang, F

    2014-02-01

    Four goats (30.1 ± 1.3 kg) with common bile duct re-entrant catheter and duodenal catheter were used to evaluate the effects of duodenal leucine infusion on pancreatic exocrine secretion and plasma parameters with two 4 × 4 Latin square design experiments. In the long-term infusion experiment, goats were fed twice daily [700 g/day, dry matter (DM) basis] at 8:00 and 18:00 hours and were duodenally infused with 0, 3, 6, 9 g/day leucine for 14 days. Pancreatic juice and jugular blood samples were collected over 1-h intervals for 6 h daily from d 11 to 14 days to encompass a 24-h day. In the short-term experiment, goats were infused leucine for 10 h continuously at the same infusion rate with Experiment 1 after feed deprivation for 24 h repeated every 10 days. Pancreatic juice and blood samples were collected at 0, 1, 2, 4, 6, 8 and 10 h of infusion. The results showed that the long-term leucine infusion did not affect pancreatic juice secretion, protein output, trypsin and lipase secretion and plasma insulin concentration, but linearly increased α-amylase secretion. No changes in pancreatic protein and lipase secretion were observed in the short-term infusion. Pancreatic juice and α-amylase secretion responded quadratically, with the greatest values observed in the 3 and 6 g/day leucine respectively. Trypsin secretion linearly decreased, while plasma insulin concentration increased linearly with increased leucine infusion. The results demonstrated that duodenal leucine infusion dose and time dependently regulated pancreatic enzyme secretion not associated with the change in plasma insulin concentration.

  6. [Effects of alcohol on the upper gastrointestinal tract and the pancreas--an up-to-date overview].

    PubMed

    Siegmund, S V; Singer, M V

    2005-08-01

    The oesophagus, stomach and pancreas are primary target organs for ethanol-related diseases. In the oesophagus and stomach, ethanol induces motility disorders and mucosal lesions that are dose-dependent and reversible under acute conditions. Chronic consumption of alcohol causes a significant increase in the risk for squamous carcinoma of the oesophagus. All of these effects are mainly caused by direct contact of alcohol or its metabolite acetaldehyde with the mucosa. Non-alcoholic components are responsible for many effects of alcoholic beverages, including the powerful stimulation of gastric acid secretion by beverages that are produced by fermentation. In the exocrine pancreas, alcohol induces secretory alterations that are mainly affected by the manner and duration of alcohol exposure, the additional administration of food, the type of beverage or the basal secretory state of the gland. Because the pancreas is not topically exposed to ethanol, these ethanol effects on pancreatic secretion are primarily caused by systemic cholinergic mechanisms of the vagus nerve. Chronic alcohol abuse may cause chronic alcoholic pancreatitis after recurrent subclinical inflammatory episodes. Genetic predispositions are believed to play an additional role in the pathomechanism of the disease. In contrast to the cardiovascular system, moderate consumption of alcoholic beverages does not have any beneficial health effects on the oesophagus, stomach or pancreas. Future research needs to define the exact molecular mechanisms and the role of different genetic predispositions for alcohol-induced diseases as well as the effects of the non-alcoholic components of alcoholic beverages.

  7. Comparison of the effects of dietary sunflower oil and virgin olive oil on rat exocrine pancreatic secretion in vivo.

    PubMed

    Díaz, Ricardo J; Yago, María D; Martínez-Victoria, Emilio; Naranjo, José A; Martínez, María A; Mañas, Mariano

    2003-11-01

    The aim of this study was to investigate the functional consequences in vivo of adapting the rat exocrine pancreas to different dietary fats. Weanling rats were fed diets containing 10 wt% virgin olive oil or sunflower oil for 8 wk. We then examined resting and cholecystokinin-octapeptide (CCK-8)-stimulated pancreatic secretion in the anesthetized animals. To confirm a direct influence of the type of fat upon the gland, the FA composition of pancreatic membranes as well as tissue protein and amylase content were determined in separate rats. The membrane FA profile was profoundly altered by the diets, reflecting the type of dietary fat given, although this was not paralleled by variations in the pancreatic content of protein or amylase. Nevertheless, dietary intake of oils evoked different effects on in vivo secretory activity. Resting flow rate and amylase output were significantly (P < 0.05) enhanced by sunflower oil feeding. Time course changes in response to CCK-8 infusion also showed a different pattern in each group. Secretion of fluid, protein, and amylase increased markedly in all animals, reaching a maximum within 20-40 min of infusion that was followed by a dramatic decline in both groups. In the sunflower oil group, this resulted in values reaching the resting level as soon as 60 min after CCK-8 infusion was begun. However, after the initial decline, olive oil group values showed a prolonged plateau elevation above the baseline (P < 0.05) that was maintained for at least the infusion time. In addition, a positive correlation between flow rate and both protein concentration and amylase activity existed in the olive oil group, but not in the sunflower oil group. The precise mechanism by which these effects are produced remains to be elucidated.

  8. Design of a bioartificial pancreas

    PubMed Central

    Pareta, Rajesh A; Farney, Alan C; Opara, Emmanuel C

    2013-01-01

    Summary Islet transplantation has been shown to be a viable treatment option for patients afflicted with Type 1 diabetes. However, the severe shortage of human pancreas and the need to use risky immunosuppressive drugs to prevent transplant rejection remain two major obstacles to routine use of islet transplantation in diabetic patients. Successful development of a bioartificial pancreas using the approach of microencapsulation with perm-selective coating of islets in hydrogels for graft immunoisolation holds tremendous promise for diabetic patients because it has great potential to overcome these two barriers. In this review article, we will discuss the need for bioartificial pancreas, provide a detailed description of the microencapsulation process, and review the status of the technology in clinical development. We will also critically review the various factors that need to be taken into consideration in order to achieve the ultimate goal of routine clinical application. PMID:23652283

  9. Pancreatic stellate cells: a starring role in normal and diseased pancreas

    PubMed Central

    Apte, Minoti V.; Pirola, Romano C.; Wilson, Jeremy S.

    2012-01-01

    While the morphology and function of cells of the exocrine and endocrine pancreas have been studied over several centuries, one important cell type in the gland, the pancreatic stellate cell (PSC), had remained undiscovered until as recently as 20 years ago. Even after its first description in 1982, it was to be another 16 years before its biology could begin to be studied, because it was only in 1998 that methods were developed to isolate and culture PSCs from rodent and human pancreas. PSCs are now known to play a critical role in pancreatic fibrosis, a consistent histological feature of two major diseases of the pancreas—chronic pancreatitis and pancreatic cancer. In health, PSCs maintain normal tissue architecture via regulation of the synthesis and degradation of extracellular matrix (ECM) proteins. Recent studies have also implied other functions for PSCs as progenitor cells, immune cells or intermediaries in exocrine pancreatic secretion in humans. During pancreatic injury, PSCs transform from their quiescent phase into an activated, myofibroblast-like phenotype that secretes excessive amounts of ECM proteins leading to the fibrosis of chronic pancreatitis and pancreatic cancer. An ever increasing number of factors that stimulate and/or inhibit PSC activation via paracrine and autocrine pathways are being identified and characterized. It is also now established that PSCs interact closely with pancreatic cancer cells to facilitate cancer progression. Based on these findings, several therapeutic strategies have been examined in experimental models of chronic pancreatitis as well as pancreatic cancer, in a bid to inhibit/retard PSC activation and thereby alleviate chronic pancreatitis or reduce tumor growth in pancreatic cancer. The challenge that remains is to translate these pre-clinical developments into clinically applicable treatments for patients with chronic pancreatitis and pancreatic cancer. PMID:22973234

  10. Perioperative Computed Tomography Assessments of the Pancreas Predict Nonalcoholic Fatty Liver Disease After Pancreaticoduodenectomy.

    PubMed

    Ohgi, Katsuhisa; Okamura, Yukiyasu; Yamamoto, Yusuke; Ashida, Ryo; Ito, Takaaki; Sugiura, Teiichi; Aramaki, Takeshi; Uesaka, Katsuhiko

    2016-02-01

    Nonalcoholic fatty liver disease (NAFLD) after pancreaticoduodenectomy (PD) has become a clinically important issue. Although pancreatic exocrine insufficiency has been reported to be a main cause of NAFLD after PD, a clinically practical examination to assess the pancreatic exocrine function has not been established. The aim of this study was to evaluate risk factors for NAFLD after PD with a focus on perioperative computed tomography (CT) assessments of the pancreas.A retrospective review of 245 patients followed for more than 6 months after PD was conducted. We evaluated several pancreatic CT parameters, including the pancreatic parenchymal thickness, pancreatic duct-to-parenchymal ratio, pancreatic attenuation, and remnant pancreatic volume (RPV) on pre- and/or postoperative CT around 6 months after surgery. The variables, including the pancreatic CT parameters, were compared between the groups with and without NAFLD after PD.The incidence of NAFLD after PD was 19.2%. A multivariate analysis identified 5 independent risk factors for NAFLD after PD: a female gender (odds ratio [OR] 5.66, P < 0.001), RPV < 12 mL (OR 4.73, P = 0.001), preoperative pancreatic attenuation of <30 Hounsfield units (OR 4.50, P = 0.002), dissection of the right-sided nerve plexus around the superior mesenteric artery (OR 3.02, P = 0.017) and a preoperative serum carbohydrate antigen 19-9 level of ≥70 U/mL (OR 2.58, P = 0.029).Our results showed that 2 pancreatic CT parameters, the degree of preoperative pancreatic attenuation and RPV, significantly influence the development of NAFLD after PD. Perioperative CT assessments of the pancreas may be helpful for predicting NAFLD after PD.

  11. Queen Specific Exocrine Glands in Legionary Ants and Their Possible Function in Sexual Selection

    PubMed Central

    Hölldobler, Bert

    2016-01-01

    The colonies of army ants and some other legionary ant species have single, permanently wingless queens with massive post petioles and large gasters. Such highly modified queens are called dichthadiigynes. This paper presents the unusually rich exocrine gland endowment of dichthadiigynes, which is not found in queens of other ant species. It has been suggested these kinds of glands produce secretions that attract and maintain worker retinues around queens, especially during migration. However, large worker retinues also occur in non-legionary species whose queens do not have such an exuberance of exocrine glands. We argue and present evidence in support of our previously proposed hypothesis that the enormous outfit of exocrine glands found in dichthadiigynes is due to sexual selection mediated by workers as the main selecting agents. PMID:26986740

  12. Possible link between ectopic pancreas and holoprosencephaly.

    PubMed

    Kin, Tatsuya; Korbutt, Gregory S; Shapiro, A M James

    2012-01-01

    We report on the incidental observation of ectopic pancreas in a donor for islet cell transplantation. The donor's clinical and imaging presentation was definitive for holoprosencephaly. This case report discusses a possible link between ectopic pancreas and holoprosencephaly.

  13. Lymphoepithelial cyst of the pancreas.

    PubMed Central

    Gafă, R; Grandi, E; Cavazzini, L

    1997-01-01

    A rare case of lymphoepithelial cyst of the pancreas is reported. Microscopically the cyst content consisted of keratinous material and the walls were lined by mature squamous epithelium surrounded by dense lymphoid tissue. Immunohistochemistry showed diffuse reactivity for CD20 and CD3 in the lymphoid tissue and uniform positivity for cytokeratins in the squamous epithelium. Although the histogenesis of lymphoepithelial cysts of the pancreas is not understood, awareness of this lesion is helpful in differentiating it from other pancreatic cystic lesions. Images PMID:9389985

  14. The economics of pancreas surgery.

    PubMed

    Vollmer, Charles M

    2013-06-01

    Pancreas surgery is a paradigm for high-acuity surgical specialization. Given the current intrigue over containing health care expenditures, pancreas surgery provides an ideal model to investigate the cost of care. This article explores the economics of this field from literature accrued over the last 2 decades. The cost of performing a pancreatic resection is established and then embellished with a discussion of the effects of clinical care paths. Then the influence of complications on costs is explored. Next, cost is investigated as an emerging outcome metric regarding variations in pancreatic surgical care. Finally, the societal-level fiscal impact is considered.

  15. Lymphoepithelial Cyst of the Pancreas

    PubMed Central

    Arumugam, Prabhu; Fletcher, Natalie; Kyriakides, Charis; Mears, Lisa; Kocher, Hemant M.

    2016-01-01

    Lymphoepithelial cyst (LEC) of the pancreas is an extremely rare, benign pancreatic cystic lesion that is difficult to differentiate preoperatively from other cystic pancreatic lesions. LEC may have malignant potential. Here, we describe a case of LEC of the pancreas – initially suspected to be a mucinous cyst neoplasm – in an elderly man presenting with abdominal pain, who went on to have a distal pancreatectomy and splenectomy. We also review the relevant literature and discuss implications for the diagnosis and management of this rare lesion. PMID:27403123

  16. The fecal microbiome of dogs with exocrine pancreatic insufficiency.

    PubMed

    Isaiah, Anitha; Parambeth, Joseph Cyrus; Steiner, Jörg M; Lidbury, Jonathan A; Suchodolski, Jan S

    2017-02-20

    Exocrine pancreatic insufficiency (EPI) in dogs is a syndrome of inadequate synthesis and secretion of pancreatic enzymes. Small intestinal bacterial dysbiosis occurs in dogs with EPI, and is reversed with pancreatic enzyme therapy. However, there are no studies evaluating the fecal microbiome of dogs with EPI. The objective of this study was to evaluate the fecal microbiome of dogs with EPI. Three day pooled fecal samples were collected from healthy dogs (n = 18), untreated (n = 7) dogs with EPI, and dogs with EPI treated with enzyme replacement therapy (n = 19). Extracted DNA from fecal samples was used for Illumina sequencing of the bacterial 16S rRNA gene and analyzed using Quantitative Insights Into Microbial Ecology (QIIME) and PICRUSt was used to predict the functional gene content of the microbiome. Linear discriminant analysis effect size (LEfSe) revealed significant differences in bacterial groups and functional genes between the healthy dogs and dogs with EPI. There was a significant difference in fecal microbial communities when healthy dogs were compared to treated and untreated dogs with EPI (unweighted UniFrac distance, ANOSIM P = 0.001, and 0.001 respectively). Alpha diversity was significantly decreased in untreated and treated EPI dogs when compared to the healthy dogs with respect to Chao1, Observed OTU, and Shannon diversity (P = 0.008, 0.003, and 0.002 respectively). The families Bifidobacteriaceae (P = 0.005), Enterococcaceae (P = 0.018), and Lactobacillaceae (P = 0.001) were significantly increased in the untreated and treated dogs with EPI when compared to healthy dogs. In contrast, Lachnospiraceae (P < 0.001), and Ruminococcaceae (P < 0.01) were significantly decreased in dogs with EPI. Dogs with EPI (before treatment) had significant increases in functional genes associated with secretion system, fatty acid metabolism, and phosphotransferase system. In contrast, healthy dogs had a significant increase in genes related

  17. Exocrine pancreatic insufficiency in diabetes mellitus: a complication of diabetic neuropathy or a different type of diabetes?

    PubMed

    Hardt, Philip D; Ewald, Nils

    2011-01-01

    Pancreatic exocrine insufficiency is a frequently observed phenomenon in type 1 and type 2 diabetes mellitus. Alterations of exocrine pancreatic morphology can also be found frequently in diabetic patients. Several hypotheses try to explain these findings, including lack of insulin as a trophic factor for exocrine tissue, changes in secretion and/or action of other islet hormones, and autoimmunity against common endocrine and exocrine antigens. Another explanation might be that diabetes mellitus could also be a consequence of underlying pancreatic diseases (e.g., chronic pancreatitis). Another pathophysiological concept proposes the functional and morphological alterations as a consequence of diabetic neuropathy. This paper discusses the currently available studies on this subject and tries to provide an overview of the current concepts of exocrine pancreatic insufficiency in diabetes mellitus.

  18. Exocrine Pancreatic Insufficiency in Diabetes Mellitus: A Complication of Diabetic Neuropathy or a Different Type of Diabetes?

    PubMed Central

    Hardt, Philip D.; Ewald, Nils

    2011-01-01

    Pancreatic exocrine insufficiency is a frequently observed phenomenon in type 1 and type 2 diabetes mellitus. Alterations of exocrine pancreatic morphology can also be found frequently in diabetic patients. Several hypotheses try to explain these findings, including lack of insulin as a trophic factor for exocrine tissue, changes in secretion and/or action of other islet hormones, and autoimmunity against common endocrine and exocrine antigens. Another explanation might be that diabetes mellitus could also be a consequence of underlying pancreatic diseases (e.g., chronic pancreatitis). Another pathophysiological concept proposes the functional and morphological alterations as a consequence of diabetic neuropathy. This paper discusses the currently available studies on this subject and tries to provide an overview of the current concepts of exocrine pancreatic insufficiency in diabetes mellitus. PMID:21822421

  19. The increased echogenicity of the pancreas in infants and children: the white pancreas.

    PubMed

    Schneider, K; Harms, K; Fendel, H

    1987-09-01

    An increased echogenicity of the pancreas ("white pancreas") was sonographically found in 25 children with various pancreatic and systemic diseases. Fifteen patients with cystic fibrosis had a small white pancreas. Five patients with haemosiderosis, two with pancreatitis and one with Shwachman-syndrome presented with a normal-sized or slightly enlarged pancreas. Fatty infiltration and calcifications of the pancreas can also increase its echogenicity.

  20. Morphology of the pancreas of some species belonging to the genera Phelsuma and Gecko (family Gekkonidae): evidence of apoptotic process during the seasonal cycle.

    PubMed

    Buono, S; Odierna, G; Putti, R

    2006-10-01

    In this study we investigated comparative morphology of the endocrine pancreas of several species belonging to the family Gekkonidae and apoptotic processes of the pancreas which may be correlated to the seasonal cycle. The following species of the family Gekkonidae were studied: Phelsuma lineata, P. madagascariensis, P. dubia, P. abotti, Gekko gecko, G. vittatus, and Geckonia chazaliae. In all these species the pancreas consisted of large and medium islets as well as endocrine cells which were scattered throughout the acinar cells. Exocrine parenchyma consisted of tubuli-acini. Four mayor cell types were identified in the endocrine pancreas, using immunocytochemistry: glucagon-immunoreactive (A) cells, insulin-immunoreactive (B) cells, somatostatin-immunoreactive (D) cells, and pancreatic polypeptide immunoreactive (PP) cells. In the endocrine pancreas the amount of A cells and B cells was either equal or a prevalence of A cells was observed. In the wet season the pancreatic morphology presented normal features with very rare apoptotic cells. The animals belonging to the genus Phelsuma taken in the dry season (July) showed numerous vacuolated, Caspase 3, 9 and 11-immunoreactive acinar and some endocrine cells containing picnotic nuclei which were positive to tunel reaction. The animals belonging to the genus Gekko taken at the end of the dry season (October) exhibited strongly vacuolated, Caspase 3, 9 and 11-immunoreactive endocrine and some acinar cells containing nuclei which were positive to tunel reaction. These apoptosis events could be a reaction in response to stress mechanisms, such as a starvation period during the dry season.

  1. Cystic tumors of the pancreas

    PubMed Central

    Morana, Giovanni; Guarise, Alessandro

    2006-01-01

    Cystic tumors of the pancreas are less frequent than solid lesions and are often detected incidentally, as many of these lesions are small and asymptomatic. However, they may be associated with pancreatitis or have malignant potential. With advancements in diagnostic imaging, cystic lesions of the pancreas are being detected with increasing frequency. Many lesions can cause a pancreatic cyst, most being non-neoplastic while approximately 10% are cystic tumors, ranging from benign to highly malignant tumors. With increasing experience it is becoming clear that the prevalence of pseudocyst among cystic lesions of the pancreas is lower than usually presumed. A presumptive diagnosis of pseudocyst based on imaging appearance alone can cause a diagnostic error, and neoplastic cysts of the pancreas are particularly susceptible to this misdiagnosis, which can result in inappropriate treatment. Cystic tumors of the pancreas are formed by serous or mucinous structures showing all stages of cellular differentiation. According to the WHO classification, they can be subdivided on the basis of their histological type and biological behavior into benign tumors, borderline tumors, and malignant tumors. Cystic pancreatic tumors can be subdivided into peripheral (serous cystadenomas, mucinous cystic tumors, solid and papillary epithelial neoplasms, cystic islet cell tumors), which do not communicate with the main pancreatic duct, and ductal tumors (mucinous tumor), according to their site of origin. On the basis of imaging criteria alone, it can be very difficult to differentiate non-tumoral cystic lesions from neoplastic ones. The management of these patients is complex, and it is important to correlate imaging findings with knowledge of the patient’s symptoms and of the natural history and predictors of malignancy in pancreatic cysts. PMID:16861136

  2. Guilty Knowledge versus Innocent Associations: Effects of Trait Anxiety and Stimulus Context on Skin Conductance.

    ERIC Educational Resources Information Center

    Giesen, Martin; Rollison, Michael A.

    1980-01-01

    Simulated lie detection procedure investigated skin conductance responsivity among self-reported skin responders. Subjects grouped by trait anxiety engaged in mock crime providing "guilty knowledge" or in neutral activity providing "innocent associations" and were interrogated using Lykken's Guilty Knowledge technique.…

  3. "Suited to Their Needs": White Innocence as a Vestige of Segregation

    ERIC Educational Resources Information Center

    Orozco, Richard; Jaime Diaz, Jesus

    2016-01-01

    Discourses that supported de jure segregated schools often invoked White innocence in the form of altruistic motivations. These same invocations are found in more contemporary school policy discourses. The authors of this article argue, based on the concept of intertextuality of discourse, the existence of contemporary schooling policies as…

  4. Effects of coping and cooperative instructions on guilty and informed innocents' physiological responses to concealed information.

    PubMed

    Zvi, Liza; Nachson, Israel; Elaad, Eitan

    2012-05-01

    Previous research on the Concealed Information Test indicates that knowledge of the critical information of a given event is sufficient for the elicitation of strong physiological reactions, thus facilitating detection by the test. Other factors that affect the test's efficacy are deceptive verbal responses to the test's questions and motivation of guilty examinees to avoid detection. In the present study effects of coping and cooperative instructions - delivered to guilty and innocent participants - on detection were examined. In a mock-theft experiment guilty participants who actually committed a mock-crime, and informed innocent participants who handled the critical items of the crime in an innocent context, were instructed to adopt either a coping or a cooperative attitude toward the polygraph test. Results indicated that both, guilt and coping behavior, were associated with enhanced physiological responses to the critical information, whereas innocence and cooperative behavior attenuated physiological responses. Theoretical and applied implications of the results are discussed. Copyright © 2012 Elsevier B.V. All rights reserved.

  5. Lost Innocent and Sacrificial Delegate: The JonBenet Ramsey Murder.

    ERIC Educational Resources Information Center

    Conrad, Joann

    1999-01-01

    Analyzes murder case of 6-year-old JonBenet Ramsey as emblematic of American cultural fascination with images of the innocence of children and the perfect family, and of a change in cultural self-awareness as these images prove illusionary. Considers the role of mass media in marketing a cultural fascination with sexualized images of children and…

  6. Yani: The Brush of Innocence. Teacher's Activity Packet, Grades One through Five.

    ERIC Educational Resources Information Center

    Smithsonian Institution, Washington, DC. Arthur M. Sackler Gallery.

    This document presents a teaching package designed to introduce students in grades one through five to Chinese painting methods and equipment. Prepared in conjunction with an exhibition of paintings by child prodigy Wang Yani titled "The Brush of Innocence," the package consists of a teacher's activity plan unit, a slide set of art works…

  7. Too Late for Luck: A Comparison of Post-Furman Exonerations and Executions of the Innocent

    ERIC Educational Resources Information Center

    Harmon, Talia Roitberg; Lofquist, William S.

    2005-01-01

    This study is a quantitative analysis designed to compare two groups of factually innocent capital defendants: those who were exonerated and those who were executed. There are a total of 97 cases in the sample, including 81 exonerations and 16 executions. The primary objective of the authors is to identify factors that may predict case outcomes…

  8. The penology of racial innocence: the erasure of racism in the study and practice of punishment.

    PubMed

    Murakawa, Naomi; Beckett, Katherine

    2010-01-01

    In post–civil rights America, the ascendance of “law-and-order” politics and “postracial” ideology have given rise to what we call the penology of racial innocence. The penology of racial innocence is a framework for assessing the role of race in penal policies and institutions, one that begins with the presumption that criminal justice is innocent of racial power until proven otherwise. Countervailing sociolegal changes render this framework particularly problematic. On the one hand, the definition of racism has contracted in antidiscrimination law and in many social scientific studies of criminal justice, so that racism is defined narrowly as intentional and causally discrete harm. On the other hand, criminal justice institutions have expanded to affect historically unprecedented numbers of people of color, with penal policies broadening in ways that render the identification of racial intent and causation especially difficult. Analyses employing the penology of racial innocence examine the ever-expanding criminal justice system with limited definitions of racism, ultimately contributing to the erasure of racial power. Both racism and criminal justice operate in systemic and serpentine ways; our conceptual tools and methods, therefore, need to be equally systemic and capacious.

  9. A Compromise and Resist World Feminism Analysis of the Age of innocence

    ERIC Educational Resources Information Center

    Yang, Hongyan

    2016-01-01

    Edith Wharton (1862-1937), a Pulitzer Prize winner, is a distinguished female novelist at the turn of the nineteenth and twentieth centuries. Her work "The Age of Innocence" contributes much to the formation of a female literary tradition. Wharton's subversion of male discourse can be well traced in her novel "The Age of…

  10. Too Late for Luck: A Comparison of Post-Furman Exonerations and Executions of the Innocent

    ERIC Educational Resources Information Center

    Harmon, Talia Roitberg; Lofquist, William S.

    2005-01-01

    This study is a quantitative analysis designed to compare two groups of factually innocent capital defendants: those who were exonerated and those who were executed. There are a total of 97 cases in the sample, including 81 exonerations and 16 executions. The primary objective of the authors is to identify factors that may predict case outcomes…

  11. "Suited to Their Needs": White Innocence as a Vestige of Segregation

    ERIC Educational Resources Information Center

    Orozco, Richard; Jaime Diaz, Jesus

    2016-01-01

    Discourses that supported de jure segregated schools often invoked White innocence in the form of altruistic motivations. These same invocations are found in more contemporary school policy discourses. The authors of this article argue, based on the concept of intertextuality of discourse, the existence of contemporary schooling policies as…

  12. Lost proof of innocence: The impact of confessions on alibi witnesses.

    PubMed

    Marion, Stéphanie B; Kukucka, Jeff; Collins, Carisa; Kassin, Saul M; Burke, Tara M

    2016-02-01

    The present study investigated how alibi witnesses react in the face of an innocent suspect's confession. Under the pretext of a problem-solving study, a participant and confederate completed a series of tasks in the same testing room. The confederate was subsequently accused of stealing money from an adjacent office during the study session. After initially corroborating the innocent confederate's alibi that she never left the testing room, only 45% of participants maintained their support of that alibi once informed that the confederate had confessed (vs. 95% when participants believed the confederate had denied involvement). Even fewer (20%) maintained their corroboration when the experimenter insinuated that their support of the alibi might imply their complicity. The presence of a confession also decreased participants' confidence in the accuracy of the alibi and their belief in the confederate's innocence. These findings suggest that a police-induced confession can strip an innocent confessor of a vital source of exculpatory evidence. This effect may well explain the often-puzzling absence of exculpatory evidence in many cases involving wrongful conviction.

  13. Guilty Knowledge versus Innocent Associations: Effects of Trait Anxiety and Stimulus Context on Skin Conductance.

    ERIC Educational Resources Information Center

    Giesen, Martin; Rollison, Michael A.

    1980-01-01

    Simulated lie detection procedure investigated skin conductance responsivity among self-reported skin responders. Subjects grouped by trait anxiety engaged in mock crime providing "guilty knowledge" or in neutral activity providing "innocent associations" and were interrogated using Lykken's Guilty Knowledge technique.…

  14. Lost Innocent and Sacrificial Delegate: The JonBenet Ramsey Murder.

    ERIC Educational Resources Information Center

    Conrad, Joann

    1999-01-01

    Analyzes murder case of 6-year-old JonBenet Ramsey as emblematic of American cultural fascination with images of the innocence of children and the perfect family, and of a change in cultural self-awareness as these images prove illusionary. Considers the role of mass media in marketing a cultural fascination with sexualized images of children and…

  15. Who Are the "Innocent Victims?" Using NEXIS To Track the "New York Times'" Coverage of AIDS.

    ERIC Educational Resources Information Center

    Siegel, Paul

    A study measured attitudes towards Acquired Immune Deficiency Syndrome (AIDS) victims by providing a qualitative content analysis of newspaper coverage of the epidemic. A search of the NEXIS database was conducted to identify every "New York Times" article on the subject of AIDS in which the word "innocent" appears. Results…

  16. 33 CFR 151.2015 - Is a vessel in innocent passage exempt from the mandatory requirements?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Is a vessel in innocent passage exempt from the mandatory requirements? 151.2015 Section 151.2015 Navigation and Navigable Waters COAST... SUBSTANCES, GARBAGE, MUNICIPAL OR COMMERCIAL WASTE, AND BALLAST WATER Ballast Water Management for Control of...

  17. Common spectrum of polypeptides occurs in secretion granule membranes of different exocrine glands

    SciTech Connect

    Cameron, R.S.; Cameron, P.L.; Castle, J.D.

    1986-10-01

    A highly purified membrane preparation from rat parotid secretion granules has been used as a comparative probe to examine the extent of compositional overlap in granule membranes of three other exocrine secretory tissues - pancreatic, lacrimal, and submandibular - from several standpoints. First, indirect immunofluorescent studies using a polyclonal polyspecific anti-parotid granule membrane antiserum has indicated a selective staining of granule membrane profiles in all acinar cells of all tissues. Second, highly purified granule membrane subfractions have been isolated from each exocrine tissue; comparative two-dimensional (isoelectric focusing; SDS) PAGE of radioiodinated granule membranes has identified 10-15 polypeptides of identical pI and apparent molecular mass. These species are likely to be integral membrane components since they are not extracted by either saponin-sodium sulfate or sodium carbonate (pH 11.5) treatments, and they do not have counterparts in the granule content. Finally, the identity among selected parotid and pancreatic radioiodinated granule membrane polypeptides has been documented using two-dimensional peptide mapping of chymotryptic and tryptic digests. These findings clearly indicate that exocrine secretory granules, irrespective of the nature of stored secretion, comprise a type of vesicular carrier with a common (and probably refined) membrane composition. Conceivably, the polypeptides identified carry out general functions related to exocrine secretion.

  18. ESPGHAN and NASPGHAN Report on the Assessment of Exocrine Pancreatic Function and Pancreatitis in Children.

    PubMed

    Taylor, Christopher J; Chen, Kathy; Horvath, Karoly; Hughes, David; Lowe, Mark E; Mehta, Devendra; Orabi, Abrahim I; Screws, Jeremy; Thomson, Mike; Van Biervliet, Stephanie; Verkade, Henkjan J; Husain, Sohail Z; Wilschanski, Michael

    2015-07-01

    The purpose of this clinical report is to discuss several recent advances in assessing exocrine pancreatic insufficiency (EPI) and pancreatitis in children, to review the array of pancreatic function tests, to provide an update on the inherited causes of EPI, with special emphasis on newly available genetic testing, and to review newer methods for evaluating pancreatitis.

  19. Pancrelipase: an evidence-based review of its use for treating pancreatic exocrine insufficiency.

    PubMed

    Nakajima, Kei; Oshida, Haruki; Muneyuki, Toshitaka; Kakei, Masafumi

    2012-01-01

    Pancreatic exocrine insufficiency (PEI) is often observed in patients with pancreatic diseases, including chronic pancreatitis, cystic fibrosis, and tumors, or after surgical resection. PEI often results in malnutrition, weight loss and steatorrhea, which together increase the risk of morbidity and mortality. Therefore, nutritional interventions, such as low-fat diets and pancreatic enzyme replacement therapy (PERT), are needed to improve the clinical symptoms, and to address the pathophysiology of pancreatic exocrine insufficiency. PERT with delayed-release pancrelipase is now becoming a standard therapy for pancreatic exocrine insufficiency because it significantly improves the coefficients of fat and nitrogen absorption as well as clinical symptoms, without serious treatment-emergent adverse events. The major adverse events were tolerable gastrointestinal tract symptoms, such as stomach pain, nausea, and bloating. Fibrosing colonopathy, a serious complication, is associated with high doses of enzymes. Several pancrelipase products have been approved by the US Food and Drug Administration in recent years. Although many double-blind, placebo-controlled trials of pancrelipase products have been conducted in recent years, these studies have enrolled relatively few patients and have often been less than a few weeks in duration. Moreover, few studies have addressed the issue of pancreatic diabetes, a type of diabetes that is characterized by frequent hypoglycemia, which is difficult to manage. In addition, it is unclear whether PERT improves morbidity and mortality in such settings. Therefore, large, long-term prospective studies are needed to identify the optimal treatment for pancreatic exocrine insufficiency. The studies should also examine the extent to which PERT using pancrelipase improves mortality and morbidity. The etiology and severity of pancreatic exocrine insufficiency often differ among patients with gastrointestinal diseases or diabetes (type 1 and type

  20. Pancreaticoduodenectomy for pancreas carcinoma occurring in the annular pancreas: report of a case.

    PubMed

    Kawaida, Hiromichi; Kono, Hiroshi; Watanabe, Mitsuaki; Maki, Akira; Amemiya, Hidetake; Matsuda, Masanori; Fujii, Hideki; Fukasawa, Mitsuharu; Takahashi, Ei; Sano, Katsuhiro; Inoue, Tomohiro

    2015-08-01

    The annular pancreas is a rare congenital anomaly in which a ring of the pancreas parenchyma surrounds the second part of the duodenum. Malignant tumors are extremely rare in patients with an annular pancreas. A 64-year-old man presented with appetite loss and vomiting. Abdominal contrast-enhanced computed tomography (CT) indicated pancreas parenchyma surrounding the second part of the duodenum, and a hypovascular area occupying lesion in the annular pancreas. Subtotal stomach-preserving pancreaticoduodenectomy was performed. Histopathology showed pancreatic carcinoma occurring in the complete annular pancreas.

  1. Positron emission tomography ligand [11C]5-hydroxy-tryptophan can be used as a surrogate marker for the human endocrine pancreas.

    PubMed

    Eriksson, Olof; Espes, Daniel; Selvaraju, Ram K; Jansson, Emma; Antoni, Gunnar; Sörensen, Jens; Lubberink, Mark; Biglarnia, Ali-Reza; Eriksson, Jan W; Sundin, Anders; Ahlström, Håkan; Eriksson, Barbro; Johansson, Lars; Carlsson, Per-Ola; Korsgren, Olle

    2014-10-01

    In humans, a well-developed serotonin system is localized to the pancreatic islets while being absent in exocrine pancreas. Assessment of pancreatic serotonin biosynthesis could therefore be used to estimate the human endocrine pancreas. Proof of concept was tested in a prospective clinical trial by comparisons of type 1 diabetic (T1D) patients, with extensive reduction of β-cells, with healthy volunteers (HVs). C-peptide-negative (i.e., insulin-deficient) T1D subjects (n = 10) and HVs (n = 9) underwent dynamic positron emission tomography with the radiolabeled serotonin precursor [(11)C]5-hydroxy-tryptophan ([(11)C]5-HTP). A significant accumulation of [(11)C]5-HTP was obtained in the pancreas of the HVs, with large interindividual variation. A substantial and highly significant reduction (66%) in the pancreatic uptake of [(11)C]5-HTP in T1D subjects was observed, and this was most evident in the corpus and caudal regions of the pancreas where β-cells normally are the major constituent of the islets. [(11)C]5-HTP retention in the pancreas was reduced in T1D compared with nondiabetic subjects. Accumulation of [(11)C]5-HTP in the pancreas of both HVs and subjects with T1D was in agreement with previously reported morphological observations on the β-cell volume, implying that [(11)C]5-HTP retention is a useful noninvasive surrogate marker for the human endocrine pancreas. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  2. Impact of pancreatic venous drainage site on long-term patient and graft outcome in simultaneous pancreas-kidney transplantation.

    PubMed

    Petruzzo, Palmina; Lefrancois, Nicole; Berthillot, Celine; Danjou, Fabrice; Contu, Paolo; Codas, Ricardo; Morelon, Emmanuel; Dubernard, Jean Michel; Martin, Xavier; Badet, Lionel

    2008-01-01

    The impact of portal or systemic venous pancreas graft drainage on patient and graft outcome remains controversial. In the present study, the impact of venous drainage type on long-term patient and graft survival is assessed. From July 1996 to December 2002 80 simultaneous pancreas-kidney transplants were enrolled into a prospective study: 44 received a pancreas allograft with portal (P-SPK group) and 36 with systemic venous drainage (S-SPK group). Enteric exocrine drainage was performed in all recipients receiving the same immunosuppressive treatment. At one yr, the patient survival rates were 91.7% and 95.5% both for S-SPK and P-SPK groups, respectively; no significant difference in survival was shown at any time point of the follow-up. The one-, three-, five-, and eight-yr pancreas survival rates were 75%, 60.6%, 56.7%, and 44%, respectively in the S-SPK group compared to 88.6%, 84.1%, 78.4%, and 31.3% in the P-SPK group. The one-, three-, five-, and eight-yr kidney survival rates were 91.7%, 78.15%, 74.1%, and 57.9%, respectively in the S-SPK group compared to 93.2%, 88.6%, 78.4%, and 38.9% in the P-SPK group. Comparing the two groups, no significant difference was shown in the total number of surgical complications as well as in the number of each complication. No significant difference in long-term outcomes between the two groups was shown, even if in S-SPK group a higher incidence of pancreas graft loss has been reported and it was in part correlated to a higher number of graft thromboses.

  3. Application of Rotating Wall Vessel (RWV) Cell Culture for Pancreas Islet Cell Transplantation

    NASA Technical Reports Server (NTRS)

    Rutzky, Lynne P.

    1998-01-01

    Type I insulin-dependent diabetes mellitus (IDDM) remains a major cause of morbidity and mortality in both pediatric and adult populations, despite significant advances in medical management. While insulin therapy treats symptoms of acute diabetes, it fails to prevent chronic complications such as microvascular disease, blindness, neuropathy, and chronic renal failure. Strict control of blood glucose concentrations delays but does not prevent the onset and progression of secondary complications. Although, whole pancreas transplantation restores physiological blood glucose levels, a continuous process of allograft rejection causes vascular and exocrine-related complications. Recent advances in methods for isolation and purification of pancreatic islets make transplantation of islet allografts an attractive alternative to whole pancreas transplantation. However, immunosuppressive drugs are necessary to prevent rejection of islet allografts and many of these drugs are known to be toxic to the islets. Since auto-transplants of isolated islets following total pancreatectomy survive and function in vivo, it is apparent that a major obstacle to successful clinical islet transplantation is the immunogenicity of the islet allografts.

  4. Reciprocal endoderm-mesoderm interactions mediated by fgf24 and fgf10 govern pancreas development.

    PubMed

    Manfroid, Isabelle; Delporte, François; Baudhuin, Ariane; Motte, Patrick; Neumann, Carl J; Voz, Marianne L; Martial, Joseph A; Peers, Bernard

    2007-11-01

    In amniotes, the pancreatic mesenchyme plays a crucial role in pancreatic epithelium growth, notably through the secretion of fibroblast growth factors. However, the factors involved in the formation of the pancreatic mesenchyme are still largely unknown. In this study, we characterize, in zebrafish embryos, the pancreatic lateral plate mesoderm, which is located adjacent to the ventral pancreatic bud and is essential for its specification and growth. We firstly show that the endoderm, by expressing the fgf24 gene at early stages, triggers the patterning of the pancreatic lateral plate mesoderm. Based on the expression of isl1, fgf10 and meis genes, this tissue is analogous to the murine pancreatic mesenchyme. Secondly, Fgf10 acts redundantly with Fgf24 in the pancreatic lateral plate mesoderm and they are both required to specify the ventral pancreas. Our results unveil sequential signaling between the endoderm and mesoderm that is critical for the specification and growth of the ventral pancreas, and explain why the zebrafish ventral pancreatic bud generates the whole exocrine tissue.

  5. Release of NPY in pig pancreas: Dual parasympathetic and sympathetic regulation

    SciTech Connect

    Sheikh, S.P.; Holst, J.J.; Skak-Nielsen, T.; Knigge, U.; Warberg, J.; Theodorsson-Norheim, E.; Hoekfelt, T.; Lundberg, J.M.; Schwartz, T.W. Karolinska Institutet, Stockholm )

    1988-07-01

    Several lines of evidence have connected neuropeptide Y (NPY), a 36-residue polypeptide, to the sympathetic division of the autonomic nervous system. The authors studied the localization, the molecular characteristics, and the release of NPY and norepinephrine (NE) in the porcine pancreas. Immunohistochemical investigations revealed that NPY nerves around blood vessels were likely to be of adrenergic nature, whereas NPY-immunoreactive fibers close to exocrine and endocrine cells may originate from local ganglia also containing VIP (vasoactive intestinal peptide) and PHI (peptide histidine isoleucine). Electrical stimulation of the splanchnic nerve supply to the isolated perfused pig pancreas resulted in a corelease of NPY and NE into the venous effluent. Stimulation of the vagal nerves caused a sevenfold larger release of NPY without affecting the NE secretion. Characterization of the NPY immunoreactivity in the pancreatic tissue and in the venous effluent by gel filtration, high-performance liquid chromatography, and isoelectric focusing shoed that the immunoreactive NPY was indistinguishable from synthetic porcine NPY. It is concluded that, although NPY is associated with sympathetic perivascular neurons, the majority of the pancreatic NPY-containing nerve fibers are likely to belong to the parasympathetic division of the autonomic nervous system.

  6. Interdisciplinary management of an intraductal papillary mucinous neoplasm of the pancreas.

    PubMed

    Nair, Rajesh M; Barthel, James S; Centeno, Barbara A; Choi, Junsung; Klapman, Jason B; Malafa, Mokenge P

    2008-10-01

    Intraductal papillary mucinous neoplasm (IPMN) of the pancreas is less common than classic invasive ductal adenocarcinoma of the pancreas but is being diagnosed with greater frequency since its clinicopathologic features are now clearly defined. Often multifocal in its existence along the pancreatic duct, IPMN is associated with a significant risk for recurrence and warrants vigilant surveillance, even after a margin-negative resection. The authors present a case highlighting important features in the diagnosis, workup, and management of IPMN. They also review existing literature highlighting epidemiology, findings of molecular studies, and current treatment recommendations. Physicians and patients must carefully weigh the risks and benefits associated with treatment options. Limited resection in a patient with a high likelihood of multifocal disease preserves pancreatic parenchyma and reduces the risk of developing pancreatic endocrine and exocrine insufficiency. Though the risk of developing invasive cancer in the remnant is small, the prognosis is worse if it does develop. Conversely, total pancreatectomy eliminates the risk of future malignancy but involves life-long insulin and exogenous pancreatic enzyme dependence and significant associated morbidity. Decision making for effective treatment of IPMN is complex and requires attention to detail by an interdisciplinary team with experience in the diagnosis and management of these tumors. Treatment must be individualized based on patient life expectancy in terms of remaining years and overall quality. Molecular profiling of these lesions may allow for more precise tailoring of treatment in the future.

  7. Extreme subcutaneous, intramuscular and inhaled insulin resistance treated by pancreas transplantation alone.

    PubMed

    Sa, J R; Alvarenga, M A; Rangel, E B; Melaragno, C S; Gonzalez, A M; Linhares, M M; Salzedas, A; Carmona, A K; Tonetto-Fernandes, V; Gabbay, M A; Medina Pestana, J O; Dib, S A

    2010-01-01

    Diabetes mellitus with resistance to insulin administered subcutaneously or intramuscularly (DRIASM) is a rare syndrome and is usually treated with continuous intravenous insulin infusion. We present here two cases of DRIASM in 16 and 18 years female patients that were submitted to pancreas transplantation alone (PTA). Both were diagnosed with type 1 diabetes as young children and had labile glycemic control with recurrent episodes of diabetic ketoacidosis. They had prolonged periods of hospitalization and complications related to their central venous access. Exocrine and endocrine drainages were in the bladder and systemic, respectively. Both presented immediate graft function. In patient 1, enteric conversion was necessary due to reflux pancreatitis. Patient 2 developed mild postoperative hyperglycemia in spite of having normal pancreas allograft biopsy and that was attributed to her immunosuppressive regimen. Patient 1 died 9 months after PTA from septic shock related to pneumonia. In 8 months of follow-up, Patient 2 presented optimal glycemic control without the use of antidiabetic agents. In conclusion, PTA may be an alternative treatment for DRIASM patients.

  8. Effects of porcine pancreatic enzymes on the pancreas of hamsters. Part 1: basic studies.

    PubMed

    Saruc, Murat; Nozawa, Fumiaki; Yalniz, Mehmet; Itami, Atsushi; Pour, Parviz M

    2012-09-10

    Porcine pancreatic enzymes (PPE) extracted from glandular stomach has been used for the treatment of pancreatic cancer patients. Unfortunately, no information is available on the in vitro and in vivo effect on the pancreas and other tissues. We used Syrian Golden hamsters, a unique pancreatic cancer model, to obtain basic information on PPE for its eventual use for the treatment of pancreatic cancer. PPE was used in different concentrations in vitro and in vivo. The stability of the enzyme in the water solution was investigated. It was given to the hamsters by gavage in concentrations of 1g/kg and 400 mg/kg for short periods and in aqueous solution for 65 days. Plasma enzyme and insulin, the size of islets and the number of the insulin cells per islet were examined. The enzyme activity of PPE was maintained in water solution for at least 24 hours. Due to its content of calcium chloride it showed a high toxicity to normal and malignant hamster pancreatic cancer cells and human pancreatic cancer cell lines in vitro. PPE did not alter the plasma pancreatic enzyme levels regardless of the dose, duration and application route. On the contrary, PPE reduced their levels significantly. Remarkably, it also reduced the level of insulin, the size of the islets and the number of insulin cells in the islets significantly. The results imply that PPE does not enter the blood circulation but it appears to slow down the function of both the exocrine and endocrine pancreas.

  9. "Ductal adenocarcinoma in anular pancreas".

    PubMed

    Benassai, Giacomo; Perrotta, Stefano; Furino, Ermenegildo; De Werra, Carlo; Aloia, Sergio; Del Giudice, Roberto; Amato, Bruno; Vigliotti, Gabriele; Limite, Gennaro; Quarto, Gennaro

    2015-09-01

    The annular pancreas is a congenital anomaly in which pancreatic tissue partially or completely surrounds the second portion of the duodenum. Its often located above of papilla of Vater (85%), rarely below (15%). This pancreatic tissue is often easily dissociable to the duodenum but there is same cases where it the tissue is into the muscolaris wall of the duodenum. We describe three case of annular pancreas hospitalized in our facility between January 2004 and January 2009. There were 2 male 65 and 69 years old respectively and 1 female of 60 years old, presented complaining of repeated episodes of mild epigastric pain. Laboratory tests (including tumor markers), a direct abdomen X-ray with enema, EGDS and total body CT scan were performed to study to better define the diagnosis. EUS showed the presence of tissue infiltrating the muscle layer all around the first part of duodenum. Biopsies performed found the presence of pancreatic tissue with focal areas of adenocarcinoma. Subtotal gastrectomy with Roux was performed. The histological examinations shows an annular pancreas of D1 with multiple focal area of adenocarcinoma. (T1aN0M0). We performed a follow up at 5 years. One patients died after 36 months for cardiovascular hit. Two patients, one male and one female, was 5-years disease-free. Annular pancreas is an uncommon congenital anomaly which usually presents itself in infants and newborn. Rarely it can present in late adult life with wide range of clinical severities thereby making its diagnosis difficult. Pre-operative diagnosis is often difficult. CT scan can illustrate the pancreatic tissue encircling the duodenum. ERCP and MRCP are useful in outlining the annular pancreatic duct. Surgery still remains necessary to confirm diagnosis and bypassing the obstructed segment. Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.

  10. Toward a hybrid artificial pancreas.

    PubMed

    Friedman, E A

    1989-06-01

    Management of insulinopenic diabetic individuals centers on administration of insulin by means of multiple injections, a wearable or implantable insulin-infusion pump, or a whole-organ or segmental-pancreas transplant. Preliminary trials indicate that surgical implantation of a hybrid device containing living insulin-secreting tissue may function as a combined glucose sensor and insulin-infusion pump. By means of a chamber composed of a semipermeable membrane shaped into hollow fibers or a box surrounding endocrine tissue, pilot studies have shown that isolated islets of Langerhans, fragments of insulinoma, or a fetal pancreas retains function for days to weeks, as judged by the ability to sustain euglycemic conditions in chemically induced diabetic rats. Lacking clear proof that normalizing blood glucose levels will prevent vascular complications of diabetes in humans, the case for further development of a hybrid (tissue plus fabricated components) device rests mainly on optimistic extrapolation of results attained in the chemically induced diabetic rat and dog. For the minority of diabetic patients who have insulin-dependent diabetes, the benefit afforded by a bionic device establishing internal insulin release regulated by silently sensed blood glucose level is more than enough payoff for the discomfort and surgery involved in its implantation. Further trials of a hybrid artificial pancreas in the dog appear warranted as a logical extension of preliminary studies with this species.

  11. Wearable and implantable pancreas substitutes.

    PubMed

    Ricotti, Leonardo; Assaf, Tareq; Dario, Paolo; Menciassi, Arianna

    2013-03-01

    A lifelong-implanted and completely automated artificial or bioartificial pancreas (BAP) is the holy grail for type 1 diabetes treatment, and could be a definitive solution even for other severe pathologies, such as pancreatitis and pancreas cancer. Technology has made several important steps forward in the last years, providing new hope for the realization of such devices, whose feasibility is strictly connected to advances in glucose sensor technology, subcutaneous and intraperitoneal insulin pump development, the design of closed-loop control algorithms for mechatronic pancreases, as well as cell and tissue engineering and cell encapsulation for biohybrid pancreases. Furthermore, smart integration of the mentioned components and biocompatibility issues must be addressed, bearing in mind that, for mechatronic pancreases, it is most important to consider how to recharge implanted batteries and refill implanted insulin reservoirs without requiring periodic surgical interventions. This review describes recent advancements in technologies and concepts related to artificial and bioartificial pancreases, and assesses how far we are from a lifelong-implanted and self-working pancreas substitute that can fully restore the quality of life of a diabetic (or other type of) patient.

  12. Differences in the readiness of guilty and informed innocent examinees to cooperate on the Guilty Action Test.

    PubMed

    Elaad, Eitan

    2014-01-01

    A mock crime experiment was designed in which 100 participants were randomly assigned to five conditions: four experimental conditions in a 2 × 2 factorial design (two guilt conditions-guilty or informed innocents, crossed with two incentive level conditions-with or without a promised reward for proving innocence), and one control condition of uninformed innocents. Along with the common dependent polygraph measures, attitudes towards cooperating with the test were assessed. Results indicated that the informed innocents preferred to cooperate whereas guilty participants preferred to try and obstruct the test. These tendencies were amplified among participants who were promised a reward. The cooperative choice attenuated electrodermal responses to the critical items. Respiration measures were sensitive to the incentive level manipulation. Implications of the results for future research and for actual detection of information tests were discussed.

  13. Pancreas Transplantation in the Modern Era.

    PubMed

    Redfield, Robert R; Rickels, Michael R; Naji, Ali; Odorico, Jon S

    2016-03-01

    The field of pancreas transplantation has evolved from an experimental procedure in the 1980s to become a routine transplant in the modern era. With short- and long-term outcomes continuing to improve and the significant mortality, quality-of-life, and end-organ disease benefits, pancreas transplantation should be offered to more patients. In this article, we review current indications, patient selection, surgical considerations, complications, and outcomes in the modern era of pancreas transplantation.

  14. CONTRAST-ENHANCED ULTRASONOGRAPHY OF THE PANCREAS IN HEALTHY DOGS AND IN DOGS WITH ACUTE PANCREATITIS.

    PubMed

    Rademacher, Nathalie; Schur, David; Gaschen, Frédéric; Kearney, Michael; Gaschen, Lorrie

    2016-01-01

    Pancreatitis is the most frequent disease affecting the exocrine pancreas in dogs and reliable diagnostic techniques for predicting fatal complications are lacking. Contrast-enhanced ultrasound (CEUS) improves detection of tissue perfusion as well as organ lesion vascular pattern. Objectives of this prospective case control study were to compare perfusion characteristics and enhancement patterns of the pancreas in healthy dogs and dogs with pancreatitis using CEUS. Ten healthy dogs and eight dogs with pancreatitis were selected based on physical examination, abdominal ultrasound, and blood analysis findings. A CEUS study of the pancreas was performed for each dog and two observers who were aware of clinical status used advanced ultrasound quantification software to analyze time-intensity curves. Perfusion patterns were compared between healthy and affected dogs. In dogs with acute pancreatitis, mean pixel and peak intensity of the pancreatic parenchyma was significantly higher than that of normal dogs (P = 0.05) in between 6 and 60 s (P = <0.0001-0.046). This corresponds to a 311% increase in mean pixel intensity in dogs with acute pancreatitis compared to healthy dogs. Wash-in rates were greater and had a consistently steeper slope to peak in dogs with pancreatitis as opposed to healthy dogs. All dogs with pancreatitis showed a decrease in pixel intensity 10-15 days after the initial examination (P = 0.011) and their times to peak values were prolonged compared to the initial exam. Findings from the current study supported the use of CEUS for diagnosing pancreatitis, pancreatic necrosis, and disease monitoring following therapy in dogs.

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

    PubMed

    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.

  16. Terror management and attributions of blame to innocent victims: reconciling compassionate and defensive responses.

    PubMed

    Hirschberger, Gilad

    2006-11-01

    In this article, 4 studies test the hypothesis that reminders of personal death bias the normative attribution process and increase the motivation to blame severely injured, innocent victims. In Studies 1 and 2, primes of death led to greater attributions of blame to severely injured victims but did not significantly influence attributions of blame to either mildly injured victims or negatively portrayed others. In Study 3, primes of death led to greater attributions of blame to victims of circumstance but did not influence attributions of blame to victims who were explicitly responsible for their condition. In Study 4, innocent victims who were severely injured elicited more death-related cognitions than did victims who were responsible for their condition or who were only mildly injured. These findings indicate that the predictions of normative models of attribution may be moderated, and even overturned, when observers are reminded of their personal death such that defensive needs override rational inferential processes.

  17. Protecting the Innocence of Youth: Moral Sanctity Values Underlie Censorship From Young Children.

    PubMed

    Anderson, Rajen A; Masicampo, E J

    2017-08-01

    Three studies examined the relationship between people's moral values (drawing on moral foundations theory) and their willingness to censor immoral acts from children. Results revealed that diverse moral values did not predict censorship judgments. It was not the case that participants who valued loyalty and authority, respectively, sought to censor depictions of disloyal and disobedient acts. Rather, censorship intentions were predicted by a single moral value-sanctity. The more people valued sanctity, the more willing they were to censor from children, regardless of the types of violations depicted (impurity, disloyalty, disobedience, etc.). Furthermore, people who valued sanctity objected to indecent exposure only to apparently innocent and pure children-those who were relatively young and who had not been previously exposed to immoral acts. These data suggest that sanctity, purity, and the preservation of innocence underlie intentions to censor from young children.

  18. [Simultaneous pancreas-kidney transplantation (SPK) for an old age male with type 2 diabetes complicated with end-stage renal disease (ESRD): a case report].

    PubMed

    Tian, Bo-le; Zhang, Zhao-da; Liu, Xu-bao; Hu, Wei-ming; Han, Fang-hai; Mai, Gang; Zhao, Ji-chun; Wang, Li; Ren, Yan; Lu, Hui-ming; Luo, Chao-zhi; Luo, Chuan-xing; Yuan, Chao-xin; Lu, Yan-rong

    2007-11-01

    We reported the first case of simultaneous pancreas-kidney transplantation (SPK) in our hospital. The recipient is a 65 year old male, who suffered type 2 diabetes for 15 years and renal dysfunction for 5 years and other diabetic complications such as retinopathy, peripheral neuropathy. SPK was performed successfully for him in March, 2007, in which the donor kidney was put in left iliac fossa, while the donor pancreas grafted to set in right iliac fossa of recipient, with pancreas exocrine drainage controlled by anastomosis to the small bowel and endocrine release done to the circulatory system. Serum C-peptide, Creatinine and Blood urea nitrogen became normal levels at day 1, 4 and 11 of post-operation respectively. The concentration of blood glucose was stabilized gradually to normal level and therefore the injected insulin was stopped using to the patient at day 16 of post-operative days. OGTT test showed the function of grafted pancreas was normal 3 weeks after transplant, and no transplantation-related complications occurred. With the recipient followed up for 6 months, both his blood glucose level and renal function maintained normal without using injected insulin, and he was getting to recover from other diabetic complications also.

  19. The innocent landowner defense under CERCLA should be transferable to subsequent purchasers

    SciTech Connect

    Spertus, J.W.

    1993-12-31

    Under CERCLA, landowners are held strictly liable for cleaning up hazardous substances on their property. Purchasers who acquire title to contaminated property become liable for cleanup costs by virtue of their status as the current owner. Although liability under the Act is strict, joint, and several, a few limited defenses enable some landowners to avoid liability altogether. One such defense, known as the innocent landowner defense, is the subject of this article.

  20. 125 Cases of duodenoduodenostomy in pancreas transplantation: a single-centre experience of an alternative enteric drainage.

    PubMed

    Walter, Martin; Jazra, Martin; Kykalos, Stylianos; Kuehn, Petra; Michalski, Stefan; Klein, Thomas; Wunsch, Andreas; Viebahn, Richard; Schenker, Peter

    2014-08-01

    Several exocrine drainage procedures have been successfully developed to perform pancreas transplantation (PT). Retroperitoneal graft placement allows exocrine drainage via direct duodenoduodenostomy (DD). This technique provides easy access for endoscopic surveillance and biopsy. A total of 241 PT procedures were performed in our centre between 2002 and 2012. DD was performed in 125 patients, and duodenojejunostomy (DJ) in 116 patients. We retrospectively compared our experience with these two types of enteric drainage, focusing on graft and patient survivals, as well as postoperative complications. With a mean follow-up of 59 months, both groups demonstrated comparable patient and graft survivals. 14 (11%) of 125 cases in the DD group and 21 (18%) of 116 cases in the DJ group had pancreatic graft loss (P = 0.142). Graft thrombosis [5 (4%) vs. 18 (16%) P = 0.002], anastomotic insufficiency [2 (1.6%) vs. 8 (7%) P = 0.052] and relaparotomy [52 (41%) vs. 56 (48%) P = 0.29] occurred more frequently in the DJ group, whereas gastrointestinal bleeding [14 (11%) vs. 4 (3%) P = 0.026] occurred more often in the DD group. DD is a feasible and safe technique in PT, with no increase in enteric complications. It is equivalent to other established techniques and extends the feasibility of anastomotic sites, especially in recipients who have undergone a second transplantation. © 2014 Steunstichting ESOT.

  1. Long-term experience with ZENPEP in infants with exocrine pancreatic insufficiency associated with cystic fibrosis.

    PubMed

    Wooldridge, Jamie L; Schaeffer, David; Jacobs, David; Thieroff-Ekerdt, Ruth

    2014-11-01

    The objective of our study was to determine whether infants with cystic fibrosis who developed exocrine pancreatic insufficiency in early infancy would tolerate long-term treatment with ZENPEP (pancrelipase) delayed-release capsules, containing 3000 US Pharmacopeia units of lipase/capsule, and demonstrate consistent long-term growth. The most common treatment-emergent adverse events were diarrhea, vomiting, and constipation (mild or moderate). At study completion, median weight-for-age percentiles increased from 22nd to 49th, median length-for-age percentiles increased from 36.5th to 42nd, and median weight-for-length percentiles increased from 41.5th to 55.5th. Long-term treatment (up to 12 months) of infants with exocrine pancreatic insufficiency owing to cystic fibrosis with ZENPEP was well tolerated and associated with improved growth parameters. This is the first long-term study of pancreatic enzyme replacement therapy conducted in this patient population.

  2. Murine nonvolatile pheromones: isolation of exocrine-gland secreting Peptide 1.

    PubMed

    Kimoto, Hiroko; Touhara, Kazushige

    2013-01-01

    Our search for a substance recognized by the vomeronasal neurons revealed that the extra-orbital lacrimal gland (ELG) isolated from adult male mice produced the male-specific peptide pheromone exocrine gland-secreting peptide 1 (ESP1). The following protocol reveals how ESP1 may be extracted from the ELG, purified using anion-exchange and reverse-phase high-performance liquid chromatography (HPLC), and analyzed by mass spectrometry. This protocol has been specifically designed for the purification of ESP1, but may be modified to isolate a variety of peptides from the exocrine glands. Peptides purified in this manner may help further define the molecular mechanisms underlying pheromone communication in the vomeronasal system.

  3. The pancreas from Aristotle to Galen.

    PubMed

    Tsuchiya, Ryoichi; Kuroki, Tamotsu; Eguchi, Susumu

    2015-01-01

    The first description of the pancreas in literature is found in Aristotle's Historia Animalium, but it is modified by "so-called". Therefore, the origin is pursued more extensively. The Greek-English Lexicon recommends three treatises as a possible original source. These three and Galen's other papers are investigated. In 2005, Sachs et al. suggested an origin of the pancreas might have derived from the intestinal divination using the avian pancreas. This report is evaluated. The avian pancreas which is the intraperitoneal organ, might have been well known by the intestinal divination, and people have called the organ pankreas or kallikreas. Anatomical dissection on human body was not accepted before the Aristotle's time. "So-called pancreas" in Historia must have been interpolated by Theophrastus. He was the most faithful and reliable disciple of Aristotle and succeeded the Aristotle's school. He and Macedonian ruler of Egypt Ptolemy I had known each other and there had been a strong link between them. The contemporary Herophilus performed many public dissections on both human and animal bodies in Alexandria. He named the various parts of the human body and designated the beginning intestine as duodenum. Yet in his extant works, the pancreas is not found. It is surmised that Herophilus may be the first to recognize the human pancreas, which is fixed with retroperitoneal tissue, and he named it "so-called pancreas". Theophrastus might have interpolated Herophilus' designation in Historia Animalium. Galen also uses "so-called pancreas" to designate the human pancreas. Galen's descriptions, that is, "Nature created 'so-called pancreas 'and spread it beneath all vessels" are not generally acceptable but propose the very rare portal vein anomalies. Since the early years of the 20th century, cases with a preduodenal portal vein or a prepancreatic portal vein have been reported. Although the incidence is very rare, its surgical importance is emphasized. Copyright © 2014

  4. The impact of multiple show-ups on eyewitness decision-making and innocence risk.

    PubMed

    Smith, Andrew M; Bertrand, Michelle; Lindsay, R C L; Kalmet, Natalie; Grossman, Deborah; Provenzano, Daniel

    2014-09-01

    If an eyewitness rejects a show-up, police may respond by finding a new suspect and conducting a second show-up with the same eyewitness. Police may continue finding suspects and conducting show-ups until the eyewitness makes an identification (Study 1). Relatively low criterion-setting eyewitnesses filter themselves out of the multiple show-ups procedure by choosing the first suspect with whom they are presented (Studies 2 and 3). Accordingly, response bias was more stringent on the second show-up when compared with the first, but became no more stringent with additional show-ups. Despite this stringent shift in response bias, innocence risk increased with additional show-ups, as false alarms cumulate (Studies 2 and 3). Although unbiased show-up instructions decreased innocent suspect identifications, the numbers were still discouraging (Study 4). Given the high number of innocent suspects who would be mistakenly identified through the use of multiple show-up procedures, using such identifications as evidence of guilt is questionable. Although evidence of guilt is limited to identifications from a single show-up, practical constraints might sometimes require police to use additional show-ups. Accordingly, we propose a stronger partition between evidentiary and investigative procedures. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  5. Perspective: Innocence and due diligence: managing unfounded allegations of scientific misconduct.

    PubMed

    Goldenring, James R

    2010-03-01

    While the incidence of fraud in science is well documented, issues related to the establishment of innocence in cases of fallacious allegations remain unaddressed. In this article, the author uses his own experience to examine issues that arise when investigators are falsely accused of scientific fraud. Investigators must understand the processes in place to protect themselves against false accusations. The present system takes a position of guilty until proven innocent, a concept that is antithetical to American principles of jurisprudence. Yet this stance is acceptable as a requirement for membership in the scientific community, more reflective of the rules within a guild organization. The necessity for proof of innocence by members of the scientific community carries obligations that transcend normal legal assumptions. Scientists must safeguard their reputations by organizing and maintaining all original image files and data relevant to publications and grant proposals. Investigators must be able to provide clear documentation rapidly whenever concerns are raised during the review process. Moreover, peer-reviewed journals must be diligent not only in the identification of fraud but also in providing rapid due process for adjudication of allegations. The success of the scientific guild rules of conduct lies in the practice of due diligence by both scientists and journal editors in questions of scientific misconduct.

  6. Cybersecurity in Artificial Pancreas Experiments

    PubMed Central

    O'Keeffe, Derek T.; Maraka, Spyridoula; Basu, Ananda; Keith-Hynes, Patrick

    2015-01-01

    Abstract Medical devices have transformed modern health care, and ongoing experimental medical technology trials (such as the artificial pancreas) have the potential to significantly improve the treatment of several chronic conditions, including diabetes mellitus. However, we suggest that, to date, the essential concept of cybersecurity has not been adequately addressed in this field. This article discusses several key issues of cybersecurity in medical devices and proposes some solutions. In addition, it outlines the current requirements and efforts of regulatory agencies to increase awareness of this topic and to improve cybersecurity. PMID:25923544

  7. Cybersecurity in Artificial Pancreas Experiments.

    PubMed

    O'Keeffe, Derek T; Maraka, Spyridoula; Basu, Ananda; Keith-Hynes, Patrick; Kudva, Yogish C

    2015-09-01

    Medical devices have transformed modern health care, and ongoing experimental medical technology trials (such as the artificial pancreas) have the potential to significantly improve the treatment of several chronic conditions, including diabetes mellitus. However, we suggest that, to date, the essential concept of cybersecurity has not been adequately addressed in this field. This article discusses several key issues of cybersecurity in medical devices and proposes some solutions. In addition, it outlines the current requirements and efforts of regulatory agencies to increase awareness of this topic and to improve cybersecurity.

  8. Reduced Pancreatic Exocrine Function and Organellar Disarray in a Canine Model of Acute Pancreatitis

    PubMed Central

    Li, Qiang; Bhugul, Pravin Avinash; Huang, Xince; Liu, Lewei; Pan, Liangliang; Ni, Haizhen; Chen, Bicheng; Sun, Hongwei; Zhang, Qiyu; Hehir, Michael; Zhou, Mengtao

    2016-01-01

    The aim of the present study was to investigate the pancreatic exocrine function in a canine model and to analyze the changes in organelles of pancreatic acinar cells during the early stage of acute pancreatitis (AP). AP was induced by retrograde injection of 5% sodium taurocholate (0.5 ml/kg) into the main pancreatic duct of dogs. The induction of AP resulted in serum hyperamylasemia and a marked reduction of amylase activity in the pancreatic fluid (PF). The pancreatic exocrine function was markedly decreased in subjects with AP compared with the control group. After the induction of AP, histological examination showed acinar cell edema, cytoplasmic vacuolization, fibroblasts infiltration, and inflammatory cell infiltration in the interstitium. Electron micrographs after the induction of AP revealed that most of the rough endoplasmic reticulum (RER) were dilated and that some of the ribosomes were no longer located on the RER. The mitochondria were swollen, with shortened and broken cristae. The present study demonstrated, in a canine model, a reduced volume of PF secretion with decreased enzyme secretion during the early stage of AP. Injury of mitochondria and dilatation and degranulation of RER may be responsible for the reduced exocrine function in AP. Furthermore, the present model and results may be useful for researching novel therapeutic measures in AP. PMID:26895040

  9. Irreversible exocrine pancreatic insufficiency in alcoholic rats without chronic pancreatitis after alcohol withdrawal.

    PubMed

    Li, Jing; Zhou, Chao; Wang, Rui; Liu, Rui; Huang, Zhiyin; Tang, Chengwei

    2010-11-01

    Long-term alcohol consumption alone did not cause chronic pancreatitis (CP) but impaired exocrine pancreatic function. This study is to explore the reversibility of exocrine pancreatic insufficiency in the abstinent rats and its mechanism. Forty-eight healthy male Wistar rats were divided randomly into 4 groups: 6-month control, 6-month ethanol, 9-month control, and 9-month ethanol + withdrawal. Morphological changes of pancreatic acinar cells were observed. Pancreatic amylase and lipase were measured using an automatic biochemical analyzer. Free fatty acid (FFA) in rat intestinal chyme was measured. Cholecystokinin (CCK) levels were determined by radioimmunoassay. The expression of CCK-A receptors was quantitatively analyzed by Western blot. Alcohol-induced ultramicrostructure changes of pancreatic acinar cells, including lipid droplets, myelinoid inclusion bodies, dilated rough endoplasmic reticulums, and diminished zymogen granules, were not attenuated after alcohol abstinence. The outputs of amylase and lipase, FFA content in intestinal chyme, and the intestinal and the pancreatic CCK levels in rats were reduced after chronic alcohol intake and were still lower than the control after cessation of alcohol use. Chronic ethanol intake or abstinence did not induce any change in the expression of CCK-A receptors. Exocrine pancreatic insufficiency was irreversible in alcoholic rats without CP after alcohol withdrawal. It may be attributed to reduced pancreatic CCK, long-standing fatty infiltration, ultramicrostructure injuries in pancreatic acinar cells, and aging. Copyright © 2010 by the Research Society on Alcoholism.

  10. Diabetes mellitus, exocrine pancreatic deficiency, hypertrichosis, hyperpigmentation, and chronic inflammation: confirmation of a syndrome.

    PubMed

    Hussain, Khalid; Padidela, Raja; Kapoor, Ritika R; James, Chela; Banerjee, Kausik; Harper, John; Wilson, Louise C; Hennekam, Raoul C M

    2009-05-01

    Type 1 diabetes mellitus is characterized by dysregulation of the immune system leading to inflammation and selective destruction of pancreatic beta cells. Mild to moderate pancreatic exocrine insufficiency is found in patients with type 1 diabetes. Diabetes mellitus may also be part of a syndrome occasionally involving hair and skin abnormalities. We report our observations on two siblings with insulin-dependent diabetes, severe exocrine pancreatic deficiency, pigmented hypertrichotic skin patches with induration and chronic inflammation. The first sibling presented at the age of 9 months with hypertrichosis and hyperpigmentation, particularly on her back and legs and then developed diabetes mellitus at the age of 4 yr. The second sibling presented with exactly the same clinical features but at a later age of 12 yr. Both siblings had severe pancreatic exocrine deficiency with chronic persistent inflammation. Some of the clinical features in these siblings resemble those described by Prendiville et al. although our patients had additional features. The chronic inflammatory response in both siblings is highly suggestive of some form of immune dysregulation. The presence of consanguinity in the parents and similarity of clinical features in the siblings are suggestive of a novel autoimmune disorder, possibly secondary to autosomal recessive inheritance.

  11. Duct- to islet-cell differentiation and islet growth in the pancreas of duct-ligated adult rats.

    PubMed

    Wang, R N; Klöppel, G; Bouwens, L

    1995-12-01

    We investigated the growth of islet beta and alpha cells in adult rats which had undergone partial pancreatic duct ligation. Whereas the non-ligated head portion of the pancreas remained unaffected in terms of histology and cell population dynamics, the ligated tail part of the pancreas showed pronounced changes in histology and cell growth. These changes included replacement of exocrine acini by ductal complexes and significant growth of islet cells. Using immunocytochemistry and morphometry, we found that the beta-cell population had nearly doubled within 1 week and that a smaller, but also significant growth of the alpha-cell population had occurred. In addition, small islets and islet-cell clusters were more numerous in the pancreatic tail, indicating islet neogenesis. The bromodeoxyuridine (BrdU) pulse labelling index of beta and alpha cells increased five fold and threefold, respectively, in the tail. However, the observed beta-cell labelling index remained below 1% which was largely insufficient to explain the increased number of beta cells. This indicates that recruitment from a proliferating stem-cell compartment was the main source for the beta-cell hyperplasia. A tenfold-elevated BrdU labelling index (18%) was observed in the duct-cell compartment which was identified by specific immunostaining for cytokeratin 20. Transitional cytodifferentiation forms between duct cells expressing cytokeratin 20 and beta cells expressing insulin, or alpha cells expressing glucagon, were demonstrated by double immunostaining. Pancreatic duct ligation also induced the expression of the beta-cell-specific glucose transporter type 2 (GLUT-2) in duct cells, indicating their metaplastic state. We concluded that in this adult rat model, the proliferation and differentiation of exocrine duct cells represents the major mechanism of endocrine beta-cell neogenesis. Our study thus demonstrates that in normal adult rats islet-cell neogenesis can be reactivated by stimulation of

  12. Resection for secondary malignancy of the pancreas.

    PubMed

    Hung, Jui-Hsia; Wang, Shin-E; Shyr, Yi-Ming; Su, Cheng-Hsi; Chen, Tien-Hua; Wu, Chew-Wun

    2012-01-01

    This study tried to clarify the role of pancreatic resection in the treatment of secondary malignancy with metastasis or local invasion to the pancreas in terms of surgical risk and survival benefit. Data of secondary malignancy of the pancreas from our 19 patients and cases reported in the English literature were pooled together for analysis. There were 329 cases of resected secondary malignancy of the pancreas, including 241 cases of metastasis and 88 cases of local invasion. The most common primary tumor metastatic to the pancreas and amenable to resection was renal cell carcinoma (RCC) (73.9%). More than half (52.3%) of the primary cancers with local invasion to the pancreas were colon cancer, and nearly half (40.9%) were stomach cancer. The median metastatic interval was 84 months (7 years) for overall primary tumors and 108 months (9 years) for RCC. The 5-year survival for secondary malignancy of the pancreas after resection was 61.1% for metastasis and 58.9% for local invasion, with 72.8% for RCC metastasis, 69.0% for colon cancer, and 43.8% for stomach cancer with local invasion to the pancreas. Pancreatic resection should not be precluded for secondary malignancy of the pancreas because long-term survival could be achieved with acceptable surgical risk in selected patients.

  13. Minimally Invasive Management of Ectopic Pancreas.

    PubMed

    Vitiello, Gerardo A; Cavnar, Michael J; Hajdu, Cristina; Khaykis, Inessa; Newman, Elliot; Melis, Marcovalerio; Pachter, H Leon; Cohen, Steven M

    2017-03-01

    The management of ectopic pancreas is not well defined. This study aims to determine the prevalence of symptomatic ectopic pancreas and identify those who may benefit from treatment, with a particular focus on robotically assisted surgical management. Our institutional pathology database was queried to identify a cohort of ectopic pancreas specimens. Additional clinical data regarding clinical symptomatology, diagnostic studies, and treatment were obtained through chart review. Nineteen cases of ectopic pancreas were found incidentally during surgery for another condition or found incidentally in a pathologic specimen (65.5%). Eleven patients (37.9%) reported prior symptoms, notably abdominal pain and/or gastrointestinal bleeding. The most common locations for ectopic pancreas were the duodenum and small bowel (31% and 27.6%, respectively). Three out of 29 cases (10.3%) had no symptoms, but had evidence of preneoplastic changes on pathology, while one harbored pancreatic cancer. Over the years, treatment of ectopic pancreas has shifted from open to laparoscopic and more recently to robotic surgery. Our experience is in line with existing evidence supporting surgical treatment of symptomatic or complicated ectopic pancreas. In the current era, minimally invasive and robotic surgery can be used safely and successfully for treatment of ectopic pancreas.

  14. Skin cancer after pancreas transplantation.

    PubMed

    Spanogle, Joshua P; Kudva, Yogish C; Dierkhising, Ross A; Kremers, Walter K; Roenigk, Randall K; Brewer, Jerry D; Prieto, Mikel; Otley, Clark C

    2012-10-01

    Skin cancer in patients who have undergone pancreas transplantation (PT) has not been extensively characterized. We sought to describe the incidence, tumor burden, and risk factors for skin cancer in PT recipients at Mayo Clinic from 1998 through 2006. A retrospective study was performed by analyzing outcomes among a cohort of pancreas allograft recipients at Mayo Clinic between 1998 and 2006. Among 216 allogeneic PT recipients at 2, 5, and 10 years posttransplantation, the cumulative incidence of any skin cancer was 4.7%, 12.7%, and 19.6%; the cumulative incidence of squamous cell carcinoma was 2.8%, 10.3%, and 16.7%; and the cumulative incidence of basal cell carcinoma was 2.4%, 7.8%, and 17.4%, respectively. The cumulative incidence of a second squamous cell carcinoma developing was 56% at 2 years; the cumulative incidence of a second basal cell carcinoma developing was 36% at 2 years. Of the risk factors examined, only age and having a skin cancer before transplantation were predictive of skin cancer development. This was a retrospective study. Results from a large tertiary center may not be generalizable. Nonmelanoma skin cancers commonly occur in recipients of PT, and those patients who have a history of nonmelanoma skin cancer have a very high likelihood of further skin cancer development. Copyright © 2011 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

  15. Pancreas transplantation after bariatric surgery.

    PubMed

    Porubsky, Marian; Powelson, John A; Selzer, Don J; Mujtaba, Muhammad A; Taber, Tim; Carnes, Katerine L; Fridell, Jonathan A

    2012-01-01

    Obese transplant candidates are at increased risk for perioperative and postoperative complications. In many transplant programs, morbid obesity is considered to be an exclusion criterion for transplantation. The only potential option that would grant these patients access to transplant is weight loss. Non-operative weight loss strategies such as behavioral modifications, exercise, diet, or medication have only very limited success in achieving long-term weight loss. In contrast, bariatric surgery was shown to achieve not only more excessive weight loss, but more importantly, this weight loss can be sustained for longer periods of time. Therefore, bariatric surgery presents an attractive option for weight loss for morbidly obese transplant candidates. We report our experience with four patients who underwent bariatric surgery prior to successful pancreas transplantation. Even though gastric bypass and laparoscopic adjustable gastric band present as equivalent alternatives for weight reduction, we believe that in the population of morbidly obese diabetic patients who are possible candidates for pancreas transplantation, laparoscopic adjustable gastric band placement is the more suitable procedure. © 2011 John Wiley & Sons A/S.

  16. Enlarged pancreas: not always a cancer.

    PubMed

    Calculli, Lucia; Festi, Davide; Pezzilli, Raffaele

    2015-02-01

    Pancreatic fat accumulation has been described with various terms including pancreatic lipomatosis, pancreatic steatosis, fatty replacement, fatty infiltration, fatty pancreas, lipomatous pseudohypertrophy and nonalcoholic fatty pancreas disease. It has been reported to be associated with type 2 diabetes mellitus, acute pancreatitis, pancreatic cancer and the formation of pancreatic fistula. The real incidence of this condition is still unknown. We report a case of pancreatic steatosis in a non-obese female patient initially diagnosed with a mass in the head of the pancreas. Magnetic resonance imaging (MRI) was carried out to define the characteristics of the pancreatic mass. MRI confirmed the diagnosis of fat pancreas. Enlarged pancreas is not always a cancer, but pancreatic steatosis is characterized by pancreatic enlargement. MRI could give a definite diagnosis of pancreatic steatosis or cancer.

  17. Impact of high dietary zinc on zinc accumulation, enzyme activity and proteomic profiles in the pancreas of piglets.

    PubMed

    Pieper, R; Martin, L; Schunter, N; Villodre Tudela, C; Weise, C; Klopfleisch, R; Zentek, J; Einspanier, R; Bondzio, A

    2015-04-01

    The exocrine pancreas plays an important role in zinc homeostasis. Feeding very high (2000-3000mgzinc/kg diet) levels of zinc oxide to piglets for short periods is a common practice in the swine industry to improve performance and prevent diseases. The impact on pancreatic function and possible side effects during long-term feeding of high dietary zinc levels are still poorly understood. A total of 54 weaned piglets were either fed with low (57mg/kg, LZn), normal (164mg/kg, NZn) or high (2425mg/kg, HZn) zinc concentration in the diets. After 4 weeks of feeding, ten piglets per treatment were euthanized and pancreas samples were taken. Tissue zinc concentration and metallothionein abundance was greater with HZn compared with NZn and LZn (P<0.05). Similarly, activity of α-amylase, lipase, trypsin and chymotrypsin was higher with HZn as compared with NZn and LZn diets (P<0.05), whereas elastase activity was unchanged. Total trolox equivalent antioxidative capacity of pancreas tissue was higher with HZn diets compared with the other treatments (P<0.05). Pancreatic protein profiles of NZn and HZn fed piglets were obtained by 2D-DIGE technique and revealed 15 differentially expressed proteins out of 2100 detected spots (P<0.05). The differentially expressed proteins aldose reductase, eukaryotic elongation factor II and peroxiredoxin III were confirmed by immunoblotting. Identified proteins include zinc finger-containing transcription factors and proteins mainly associated with oxidative stress response and signal transduction in HZn compared with NZn pigs. Histologic examination however showed no morphologic changes. The results suggest that long-term supply of very high dietary zinc increases zinc and metallothionein concentration, and digestive enzyme activity, but also triggers oxidative stress reactions in the pancreas of young pigs. The data provide new insights into pancreatic function under outbalanced zinc homeostasis. Copyright © 2015 Elsevier GmbH. All rights

  18. Clinical implications of fatty pancreas: Correlations between fatty pancreas and metabolic syndrome

    PubMed Central

    Lee, Jun Seok; Kim, Sang Heum; Jun, Dae Won; Han, Jee Hye; Jang, Eun Chul; Park, Ji Young; Son, Byung Kwan; Kim, Seong Hwan; Jo, Yoon Ju; Park, Young Sook; Kim, Yong Soo

    2009-01-01

    AIM: To investigate the clinical implications of lipid deposition in the pancreas (fatty pancreas). METHODS: The subjects of this study were 293 patients who had undergone abdominal computed tomography (CT) and sonography. Fatty pancreas was diagnosed by sonographic findings and subdivided into mild, moderate, and severe fatty pancreas groups comparing to the retroperitoneal fat echogenicity. RESULTS: Fatty pancreas was associated with higher levels for visceral fat, waist circumference, aspartate aminotransferase (AST), alanine aminotransferase (ALT), total cholesterol, triglyceride, high density lipoprotein, free fatty acid, γ-GTP, insulin, and the homeostasis model assessment of insulin resistance (HOMA-IR) than the control group (P < 0.05). HOMA-IR, visceral fat, triglyceride, and ALT also tended to increase with the degree of fat deposition in the pancreas on sonography. In a multivariate logistic regression analysis, HOMA-IR, visceral fat, and ALT level were independently related to fatty pancreas after adjustment for age, body mass index, and lipid profile. The incidence of metabolic syndrome in the fatty pancreas group was significantly higher than in the control group, and the numbers of metabolic syndrome parameters were significantly higher in the fatty pancreas group (P < 0.05). CONCLUSION: Sonographic fatty pancrease showed higher insulin resistance, visceral fat area, triglyceride, and ALT levels than normal pancreases. Fatty pancreas also showed a strong correlation with metabolic syndrome. PMID:19370785

  19. Pancreas transplant imaging: how I do it.

    PubMed

    Tolat, Parag P; Foley, W Dennis; Johnson, Christopher; Hohenwalter, Mark D; Quiroz, Francisco A

    2015-04-01

    Pancreas transplantation aims to restore physiologic normoglycemia in diabetic patients with glomerulopathy and avoid or delay the onset of diabetic retinopathy and arteriopathy. Simultaneous pancreas-kidney transplant is the most common approach, using a cadaveric pancreas donation in conjunction with either cadaveric or live donor renal transplant. Alternative techniques include pancreas after kidney transplant, in which the pancreas transplant is performed some years after renal transplant. Pancreas transplant alone is utilized rarely in diabetic patients with compensated renal function. Pancreas grafts have vascular and enteric connections that vary in their anatomic approach, and understanding of this is critical for imaging with ultrasonography, computed tomography, or magnetic resonance imaging. Imaging techniques are directed to display the pancreatic transplant arterial and venous vasculature, parenchyma, and intestinal drainage pathway. Critical vascular information includes venous thrombosis (partial or complete), arterial occlusion, or aneurysm. Parenchymal abnormalities are nonspecific and occur in pancreatitis, graft rejection, and subsequent graft ischemia. Peripancreatic fluid collections include hematoma/seroma, pseudocyst, and abscess. The latter two are related to pancreatitis, duct disruption, or leak from the duodenojejunostomy. An understanding of transplant anatomy and complications will lead to appropriate use of imaging techniques to diagnose or exclude important complications.

  20. Immediate retransplantation for pancreas allograft thrombosis.

    PubMed

    Hollinger, E F; Powelson, J A; Mangus, R S; Kazimi, M M; Taber, T E; Goble, M L; Fridell, J A

    2009-04-01

    Early pancreas allograft failure most commonly results from thrombosis and requires immediate allograft pancreatectomy. Optimal timing for retransplantation remains undefined. Immediate retransplantation facilitates reuse of the same anatomic site before extensive adhesions have formed. Some studies suggest that early retransplantation is associated with a higher incidence of graft loss. This study is a retrospective review of immediate pancreas retransplants performed at a single center. All cases of pancreas allograft loss within 2 weeks were examined. Of 228 pancreas transplants, 12 grafts were lost within 2 weeks of surgery. Eleven of these underwent allograft pancreatectomy for thrombosis. One suffered anoxic brain injury and was not a retransplantation candidate, one was retransplanted at 3.5 months and nine patients underwent retransplantation 1-16 days following the original transplant. Of the nine early retransplants, one pancreas was lost to heparin-induced thrombocytopenia, one recipient died with function at 2.9 years and the other grafts continue to function at 76-1137 days (mean 572 days). One-year graft survival for early retransplantation was 89% compared to 91% for all pancreas transplants at our center. Immediate retransplantation following pancreatic graft thrombosis restores durable allograft function with outcomes comparable to first-time pancreas transplantation.

  1. Transcriptional control of mammalian pancreas organogenesis.

    PubMed

    Cano, David A; Soria, Bernat; Martín, Francisco; Rojas, Anabel

    2014-07-01

    The field of pancreas development has markedly expanded over the last decade, significantly advancing our understanding of the molecular mechanisms that control pancreas organogenesis. This growth has been fueled, in part, by the need to generate new therapeutic approaches for the treatment of diabetes. The creation of sophisticated genetic tools in mice has been instrumental in this progress. Genetic manipulation involving activation or inactivation of genes within specific cell types has allowed the identification of many transcription factors (TFs) that play critical roles in the organogenesis of the pancreas. Interestingly, many of these TFs act at multiple stages of pancreatic development, and adult organ function or repair. Interaction with other TFs, extrinsic signals, and epigenetic regulation are among the mechanisms by which TFs may play context-dependent roles during pancreas organogenesis. Many of the pancreatic TFs directly regulate each other and their own expression. These combinatorial interactions generate very specific gene regulatory networks that can define the different cell lineages and types in the developing pancreas. Here, we review recent progress made in understanding the role of pancreatic TFs in mouse pancreas formation. We also summarize our current knowledge of human pancreas development and discuss developmental pancreatic TFs that have been associated with human pancreatic diseases.

  2. Coxsackie–adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes

    PubMed Central

    Hodik, M; Anagandula, M; Fuxe, J; Krogvold, L; Dahl-Jørgensen, K; Hyöty, H; Sarmiento, L; Frisk, G

    2016-01-01

    Objectives One of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie–adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression. Design Immunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals. The expression of CAR was also examined by reverse transcription PCR on microdissected islets (n=5), exocrine tissue (n=5) and on explanted islets infected with EV or exposed to chemokines produced by EV-infected islet cells. Results An increased frequency of patients with T1D and autoantibody-positive individuals expressed CAR in the pancreas (p<0.039). CAR staining was detected more frequently in pancreatic islets from patients with T1D and autoantibody-positive subjects (15/27) compared with (6/24) non-diabetic controls (p<0.033). Also in explanted islets cultured in UV-treated culture medium from coxsackievirus B (CBV)-1-infected islets, the expression of the CAR gene was increased compared with controls. Laser microdissection of pancreatic tissue revealed that CAR expression was 10-fold higher in endocrine compared with exocrine cells of the pancreas. CAR was also expressed in explanted islets and the expression level decreased with time in culture. CBV-1 infection of explanted islets clearly decreased the expression of CAR (p<0.05). In contrast, infection with echovirus 6 did not affect the expression of CAR. Conclusions CAR is expressed in pancreatic islets of patients with T1D and the expression level of CAR is increased in explanted islets exposed to proinflammatory

  3. Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes.

    PubMed

    Hodik, M; Anagandula, M; Fuxe, J; Krogvold, L; Dahl-Jørgensen, K; Hyöty, H; Sarmiento, L; Frisk, G

    2016-01-01

    One of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie-adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression. Immunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals. The expression of CAR was also examined by reverse transcription PCR on microdissected islets (n=5), exocrine tissue (n=5) and on explanted islets infected with EV or exposed to chemokines produced by EV-infected islet cells. An increased frequency of patients with T1D and autoantibody-positive individuals expressed CAR in the pancreas (p<0.039). CAR staining was detected more frequently in pancreatic islets from patients with T1D and autoantibody-positive subjects (15/27) compared with (6/24) non-diabetic controls (p<0.033). Also in explanted islets cultured in UV-treated culture medium from coxsackievirus B (CBV)-1-infected islets, the expression of the CAR gene was increased compared with controls. Laser microdissection of pancreatic tissue revealed that CAR expression was 10-fold higher in endocrine compared with exocrine cells of the pancreas. CAR was also expressed in explanted islets and the expression level decreased with time in culture. CBV-1 infection of explanted islets clearly decreased the expression of CAR (p<0.05). In contrast, infection with echovirus 6 did not affect the expression of CAR. CAR is expressed in pancreatic islets of patients with T1D and the expression level of CAR is increased in explanted islets exposed to proinflammatory cytokines/chemokines produced by infected

  4. [Aspiration biopsy of the pancreas].

    PubMed

    Pérez Catzín, F; Gutiérrez Samperio, C; Valenzuela Tamariz, J

    1979-01-01

    Biopsy of the pancreas frequently is followed by complications, this is why the transoperative aspiration biopsy has been recomended. During the last 2 years we used this procedure in 46 patients; in each case, one or several aspirations were done in the more-representative area of the pancreatic pathology. With the aspirated material a smear was fixed and treated with H-E stain. Biopsy was negative for carcinoma in 30 patients (65.2%), positive in 12 (26.0%), insuficient material results in other 4 (8.6%) we consider that the procedure was useful in the 82.6% of the cases and help to elect more adecuate surgical tecnic. There were no complications and we concluded that this is not a harmful procedure. The correct interpretation of the citology depends on the experience of the pathologyst with this method, to increase the percentage of correct diagnosis.

  5. Glucagon in the Artificial Pancreas

    PubMed Central

    2014-01-01

    The use of glucagon, in conjunction with insulin, in a dual chamber pump (artificial pancreas, AP) is a working goal for multiple companies and researchers. However, capital investment to create, operate, and maintain facilities with sufficient scale to produce enough glucagon to treat millions of patients, at a level of profit that makes it feasible, will be substantial. It can be assumed that the marketplace will expect the daily cost of glucagon (to the consumer) to be similar to the daily cost of insulin. After one subtracts wholesaler and pharmacy markup, there may be very few dollars remaining for the drug company to cover profit, capital expenditures, marketing, burden, and other costs. Without the potential for adequate margins, manufacturers may not be willing to take the risk. Assuming that the projections discussed in this article are in the right ballpark, advance planning for the supply for glucagon needs to start today and not wait for the AP to come to market. PMID:25139825

  6. Robotic surgery of the pancreas

    PubMed Central

    Joyce, Daniel; Morris-Stiff, Gareth; Falk, Gavin A; El-Hayek, Kevin; Chalikonda, Sricharan; Walsh, R Matthew

    2014-01-01

    Pancreatic surgery is one of the most challenging and complex fields in general surgery. While minimally invasive surgery has become the standard of care for many intra-abdominal pathologies the overwhelming majority of pancreatic surgery is performed in an open fashion. This is attributed to the retroperitoneal location of the pancreas, its intimate relationship to major vasculature and the complexity of reconstruction in the case of pancreatoduodenectomy. Herein, we describe the application of robotic technology to minimally invasive pancreatic surgery. The unique capabilities of the robotic platform have made the minimally invasive approach feasible and safe with equivalent if not better outcomes (e.g., decreased length of stay, less surgical site infections) to conventional open surgery. However, it is unclear whether the robotic approach is truly superior to traditional laparoscopy; this is a key point given the substantial costs associated with procuring and maintaining robotic capabilities. PMID:25356035

  7. Robotic surgery of the pancreas.

    PubMed

    Joyce, Daniel; Morris-Stiff, Gareth; Falk, Gavin A; El-Hayek, Kevin; Chalikonda, Sricharan; Walsh, R Matthew

    2014-10-28

    Pancreatic surgery is one of the most challenging and complex fields in general surgery. While minimally invasive surgery has become the standard of care for many intra-abdominal pathologies the overwhelming majority of pancreatic surgery is performed in an open fashion. This is attributed to the retroperitoneal location of the pancreas, its intimate relationship to major vasculature and the complexity of reconstruction in the case of pancreatoduodenectomy. Herein, we describe the application of robotic technology to minimally invasive pancreatic surgery. The unique capabilities of the robotic platform have made the minimally invasive approach feasible and safe with equivalent if not better outcomes (e.g., decreased length of stay, less surgical site infections) to conventional open surgery. However, it is unclear whether the robotic approach is truly superior to traditional laparoscopy; this is a key point given the substantial costs associated with procuring and maintaining robotic capabilities.

  8. Model individualization for artificial pancreas.

    PubMed

    Messori, Mirko; Toffanin, Chiara; Del Favero, Simone; De Nicolao, Giuseppe; Cobelli, Claudio; Magni, Lalo

    2016-07-05

    The inter-subject variability characterizing the patients affected by type 1 diabetes mellitus makes automatic blood glucose control very challenging. Different patients have different insulin responses, and a control law based on a non-individualized model could be ineffective. The definition of an individualized control law in the context of artificial pancreas is currently an open research topic. In this work we consider two novel identification approaches that can be used for individualizing linear glucose-insulin models to a specific patient. The first approach belongs to the class of black-box identification and is based on a novel kernel-based nonparametric approach, whereas the second is a gray-box identification technique which relies on a constrained optimization and requires to postulate a model structure as prior knowledge. The latter is derived from the linearization of the average nonlinear adult virtual patient of the UVA/Padova simulator. Model identification and validation are based on in silico data collected during simulations of clinical protocols designed to produce a sufficient signal excitation without compromising patient safety. The identified models are evaluated in terms of prediction performance by means of the coefficient of determination, fit, positive and negative max errors, and root mean square error. Both identification approaches were used to identify a linear individualized glucose-insulin model for each adult virtual patient of the UVA/Padova simulator. The resulting model simulation performance is significantly improved with respect to the performance achieved by a linear average model. The approaches proposed in this work have shown a good potential to identify glucose-insulin models for designing individualized control laws for artificial pancreas. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. What You Need to Know about Cancer of the Pancreas

    MedlinePlus

    ... You Need To Know About™ Cancer of the Pancreas This booklet is about cancer of the pancreas, also called pancreatic cancer. There are two main ... care. This booklet covers: The anatomy of the pancreas and basics about cancer of the pancreas Treatments ...

  10. Santorinirrhage: hemosuccus pancreaticus in pancreas divisum.

    PubMed

    Vázquez-Iglesias, J L; Durana, J A; Yañez, J; Rodriguez, H; Garcia-Vallejo, L; Arnal, F

    1988-08-01

    We describe a previously unreported complication of pancreas divisum: severe and repeated episodes of gastrointestinal bleeding through the main pancreatic duct (hemosuccus pancreaticus) in a 34-yr-old woman over a period of 10 months. She had negative investigations, including a blank laparotomy, until an endoscopic retrograde cholangiopancreatography revealed a pancreas divisum with chronic pancreatitis and a small pseudocyst at the tail of the dorsal pancreas. During the procedure, bleeding through the papilla minor was observed coming from Santorini's duct. A corporocaudal pancreatectomy was done and the bleeding episodes have subsided.

  11. Action of neurotensin on size, composition, and growth of pancreas and stomach in the rat.

    PubMed

    Feurle, G E; Müller, B; Ohnheiser, G; Baća, I

    1985-12-01

    Since the gastrointestinal peptide neurotensin has a stimulatory effect on the secretion of the exocrine pancreas and an inhibitory effect on secretion and motility of the stomach, we investigated whether chronic parenteral administration of neurotensin would affect pancreatic and gastric growth. We therefore infused synthetic neurotensin subcutaneously (dose, 43 and 282 pmol X kg-1 X min-1) in 20 Wistar rats for 2 weeks using Alzet osmotic minipumps and compared pancreatic weight, DNA, RNA, protein, lipase, amylase, pancreatic polypeptide and insulin with these parameters in 10 control rats from the same litter with subcutaneously implanted plastic cylinders approximately the size of the minipumps. In another experiment, synthetic neurotensin (836 pmol X kg-1) was injected intraperitoneally three times a day for 3 days in 12 rats. Thereafter, we measured pancreatic DNA and in vitro incorporation of [3H]thymidine into pancreatic DNA. These effects were compared with the actions of caerulein and normal saline. Long term infusion of the high neurotensin dose induced an increase of pancreatic weight (control: 0.87 g, neurotensin: 1.02 g) and of DNA (control: 2.5 micrograms; neurotensin: 3.5 micrograms) and pancreatic polypeptide (control: 2.4 ng; neurotensin: 7.4 ng) contents, whereas pancreatic protein, RNA, amylase and lipase contents were not stimulated. In relation to DNA, these parameters even were significantly depressed. Insulin remained unchanged. Intraperitoneal injection of neurotensin induced an increase of pancreatic DNA content and stimulated [3H]thymidine incorporation into DNA (control: 11 000 dpm/g; neurotensin: 15 800 dpm/g pancreas). Moreover, long-term neurotensin infusion with the high dose led to a rise in protein concentration and an increase in the thickness of the gastric antrum; antral DNA concentration was insignificantly stimulated. Parenteral neurotensin in the doses and at the times administered, led therefore, to hyperplasia of the

  12. Pancreatic exocrine insufficiency, diabetes mellitus and serum nutritional markers after acute pancreatitis

    PubMed Central

    Vujasinovic, Miroslav; Tepes, Bojan; Makuc, Jana; Rudolf, Sasa; Zaletel, Jelka; Vidmar, Tjasa; Seruga, Maja; Birsa, Bostjan

    2014-01-01

    AIM: To investigate impairment and clinical significance of exocrine and endocrine pancreatic function in patients after acute pancreatitis (AP). METHODS: Patients with AP were invited to participate in the study. Severity of AP was determined by the Atlanta classification and definitions revised in 2012. Pancreatic exocrine insufficiency (PEI) was diagnosed by the concentration of fecal elastase-1. An additional work-up, including laboratory testing of serum nutritional markers for determination of malnutrition, was offered to all patients with low levels of fecal elastase-1 FE. Hemoglobin A1c or oral glucose tolerance tests were also performed in patients without prior diabetes mellitus, and type 3c diabetes mellitus (T3cDM) was diagnosed according to American Diabetes Association criteria. RESULTS: One hundred patients were included in the study: 75% (75/100) of patients had one attack of AP and 25% (25/100) had two or more attacks. The most common etiology was alcohol. Mild, moderately severe and severe AP were present in 67, 15 and 18% of patients, respectively. The mean time from attack of AP to inclusion in the study was 2.7 years. PEI was diagnosed in 21% (21/100) of patients and T3cDM in 14% (14/100) of patients. In all patients with PEI, at least one serologic nutritional marker was below the lower limit of normal. T3cDM was more frequently present in patients with severe AP (P = 0.031), but was also present in some patients with mild and moderately severe AP. PEI was present in all degrees of severity of AP. There were no statistically significantly differences according to gender, etiology and number of AP attacks. CONCLUSION: As exocrine and endocrine pancreatic insufficiency can develop after AP, routine follow-up of patients is necessary, for which serum nutritional panel measurements can be useful. PMID:25561813

  13. Variants in Solute Carrier SLC26A9 Modify Prenatal Exocrine Pancreatic Damage in Cystic Fibrosis

    PubMed Central

    Miller, Melissa R.; Soave, David; Li, Weili; Gong, Jiafen; Pace, Rhonda G.; Boëlle, Pierre-Yves; Cutting, Garry R.; Drumm, Mitchell L.; Knowles, Michael R.; Sun, Lei; Rommens, Johanna M.; Accurso, Frank; Durie, Peter R.; Corvol, Harriet; Levy, Hara; Sontag, Marci K.; Strug, Lisa J.

    2015-01-01

    Objectives To test the hypothesis that multiple constituents of the apical plasma membrane residing alongside the causal CF Transmembrane Conductance Regulator (CFTR) protein, including known cystic fibrosis (CF) modifiers SLC26A9, SLC6A14, and SLC9A3, would be associated with prenatal exocrine pancreatic damage as measured by newborn screened (NBS) IRT levels. Study design NBS IRT measures and genome-wide genotype data were available on 111 subjects from Colorado, 37 subjects from Wisconsin, and 80 subjects from France. Multiple linear regression was used to determine whether any of eight SNPs in SLC26A9, SLC6A14 and SLC9A3 were associated with IRT and whether other constituents of the apical plasma membrane contributed to IRT. Results In the Colorado sample, three SLC26A9 SNPs were associated with NBS IRT (min P = 1.16 × 10−3; rs7512462), but no SLC6A14 or SLC9A3 SNPs were associated (P > 0.05). The rs7512462 association replicated in the Wisconsin sample (P = 0.03) but not in the French sample (P = 0.76). Furthermore, rs7512462 was the top ranked apical membrane constituent in the combined Colorado and Wisconsin sample. Conclusions NBS IRT is a biomarker of prenatal exocrine pancreatic disease in patients with CF, and a SNP in SLC26A9 accounts for significant IRT variability. This suggests SLC26A9 as a potential therapeutic target to ameliorate exocrine pancreatic disease. PMID:25771386

  14. Sarcopenia is closely associated with pancreatic exocrine insufficiency in patients with pancreatic disease.

    PubMed

    Shintakuya, Ryuta; Uemura, Kenichiro; Murakami, Yoshiaki; Kondo, Naru; Nakagawa, Naoya; Urabe, Kazuhide; Okano, Keisuke; Awai, Kazuo; Higaki, Toru; Sueda, Taijiro

    The loss of skeletal muscle mass (sarcopenia) is associated with the poor prognosis of pancreatic cancer. It has been reported pancreatic exocrine insufficiency (PEI) is associated with serum nutritional markers in chronic pancreatitis. However, there has been no report about the relationship between sarcopenia and PEI. The aim of this study is to determine whether body composition, including skeletal muscle (SM), subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), intramuscular adipose tissue content (IMAC), and serum nutritional markers are associated with pancreatic exocrine function in patients with pancreatic disease. Data were collected prospectively on 132 patients with pancreatic disease. SM, SAT, VAT and IMAC were assessed by computed tomography. Patients underwent a (13)C-labeled mixed triglyceride breath test to measure pancreatic exocrine function. Serum nutritional markers were measured at the same time of (13)C-labeled mixed triglyceride breath test. Patients were stratified by quartiles according to each body component, and for each component the lowest group was defined as the lowest quartile, treating men and women separately. The lowest group for SM was defined as sarcopenia. PEI was defined as a percentage (13)CO2 cumulative dose at 7 h below 5%. Sarcopenia was associated with PEI in both men (P < 0.001) and women (P = 0.012). Serum albumin was associated with PEI in men only (P = 0.005). Among all patients, sarcopenia (P = 0.001) and serum albumin (P = 0.058) were associated with PEI. On multivariate analysis, only sarcopenia remained independently associated with PEI (P < 0.001). Sarcopenia is independently associated with PEI in patients with pancreatic disease. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  15. Blaming for a better future: future orientation and associated intolerance of personal uncertainty lead to harsher reactions toward innocent victims.

    PubMed

    Bal, Michèlle; van den Bos, Kees

    2012-07-01

    People are often encouraged to focus on the future and strive for long-term goals. This noted, the authors argue that this future orientation is associated with intolerance of personal uncertainty, as people usually cannot be certain that their efforts will pay off. To be able to tolerate personal uncertainty, people adhere strongly to the belief in a just world, paradoxically resulting in harsher reactions toward innocent victims. In three experiments, the authors show that a future orientation indeed leads to more negative evaluations of an innocent victim (Study 1), enhances intolerance of personal uncertainty (Study 2), and that experiencing personal uncertainty leads to more negative evaluations of a victim (Study 3). So, while a future orientation enables people to strive for long-term goals, it also leads them to be harsher toward innocent victims. One underlying mechanism causing these reactions is intolerance of personal uncertainty, associated with a future orientation.

  16. Engineering of ruthenium(II) oxy- and carboxyamido-quinolate non-innocent ligand photosensitizers for dye sensitized solar cells.

    PubMed

    Ngo, Ken Tue; Lee, Nicholas A; Pinnace, Sashari; Rochford, Jonathan

    2017-02-11

    An alternative approach towards the replacement of the isothiocyantate ligands of the N3 photosensitizer with light-harvesting bidentate ligands is investigated for application in dye-sensitized solar cells. An in depth theoretical analysis has been applied to inform on the optical and redox properties of four non-innocent ligand platforms which is corroborated with experiment. Taking advantage of the 5- and 7-positions of 8-oxyquinolate, or the carboxyaryl ring system of the N-arylcarboxy-8-amidoquinolate ligand, fluorinated aryl substituents are demonstrated as an effective means to tune complex redox potentials and light harvesting properties. The non-innocent character derived from covalent mixing of both the central metal d(pi) and ligand-(pi) manifolds generates hybrid metal-ligand frontier orbitals that play a major role in contributing to the redox properties and visible electronic transitions, and promote an improved power conversion efficiency in a Ru non-innocent ligand sensitized DSSC device.

  17. Calcium-dependent photodynamic action of di- and tetrasulphonated aluminium phthalocyanine on normal and tumour-derived rat pancreatic exocrine cells.

    PubMed Central

    al-Laith, M.; Matthews, E. K.

    1994-01-01

    Important differences exist in the responses to photodynamic agents of normal and tumour-derived pancreatic acinar cells. In the present study amylase release has been used to assess the mechanisms by which the photodynamic drugs tetra- and disulphonated aluminium phthalocyanine (A1PcS4, A1PcS2) act on pancreatic cells via energy and calcium-dependent activation and transduction pathways. The photodynamic release of amylase was found to be energy dependent and inhibited by the chelation of free cytoplasmic calcium but not by the removal of extracellular calcium. In contrast to their effects on normal acinar cells, the photodynamic action of A1PcS4 and A1PcS2 was to inhibit amylase secretion from pancreatoma AR4-2J cells. Removal of extracellular calcium reversed this inhibitory effect on AR4-2J cells and produced a significant increase in amylase release, but chelation of free cytoplasmic calcium did not affect the inhibitory photodynamic action of the phthalocyanines on amylase release from the tumour cells. Overall, these results demonstrate further important distinctions between the photodynamic action of sulphonated aluminium phthalocyanines on normal versus tumour exocrine cells of the pancreas and indicate that calcium plays an important role in photodynamic drug action, since these agents affected intracellular calcium mobilisation at some distal point in the membrane signal transduction pathway for regulated secretion. Furthermore, the photodynamic inhibition of constitutive secretion in tumour cells may involve a calcium-dependent membrane target site or modulation of membrane calcium channels by activation of protein kinase C. PMID:7524603

  18. Juvenile diabetes mellitus accompanied by exocrine pancreatic insufficiency in a dog.

    PubMed

    Kang, Ji-Houn; Na, Ki-Jeong; Mo, In-Pil; Chang, Dongwoo; Yang, Mhan-Pyo

    2008-12-01

    A 6-month-old male crossbred dog weighing 0.78 kg was presented with acute bilateral immature cataracts, intermittent diarrhea and growth retardation. The clinical manifestations and laboratory findings were suggestive of concurrent juvenile diabetes mellitus (DM) and exocrine pancreatic insufficiency (EPI). Moreover, the DM was associated with a decreased level of serum insulin-like growth factor I. Histological examination revealed a markedly lower number of pancreatic islets and acinar cells. This case shows that juvenile-onset DM can occur simultaneously with EPI and result in growth retardation, acute cataract formation and a high cortisol concentration.

  19. ENDOCRINE FUNCTION OF THE SURGICALLY REDUCED PANCREAS

    PubMed Central

    Houssay, B. A.; Foglia, V. G.; Smyth, F. S.

    1941-01-01

    The pancreas reduced to 4 or 10 gm. weeks or months previously by partial resection, is able to maintain a normal glycemic level in dogs of about 10 kilos in good condition. When the pancreas is reduced to 4 gm. the capacity for secreting insulin under certain conditions of strain is diminished whereas a pancreas reduced to 10 gm. may have a normal or decreased capacity. This decreased functional capacity is shown: (1) by a longer hyperglycemic curve after the intravenous injection of 1 gm. of glucose per kilo; (2) by the requirement of smaller doses of extract of anterior hypophysis to produce diabetes; and (3) by the longer time required to correct the diabetic hyperglycemia if reduced pancreas is grafted in the neck of pancreatectomized animals. The time to recover is in inverse ratio to the weight of the transplanted pancreatic tissue. PMID:19871135

  20. [Pancreas transplant in Spain: better late than...].

    PubMed

    Casanova, Daniel

    2010-01-01

    Pancreas transplant is the only method that enables diabetic patients to have a normal carbohydrate metabolism in the long-term. Its application in selected patients has shown to have patient survival rates, at one year of the graft, similar to those transplanted with other solid organs, such as kidney, heart, liver, etc. The indications are currently well established, with combined pancreas-kidney transplant being the most common, followed by pancreas transplant after a functioning kidney transplant and isolated pancreas transplant in pre-uraemic patients. In 2005, in Spain, under the auspices of the National Transplant Organisation (ONT), a consensus meeting was held with the scientific societies involved in this type of transplant, to standardise its indications and highlight its benefits in order to optimise the results of this transplant in our country. The most important conclusions of this consensus meeting are discussed in this short article. Copyright 2008 AEC. Published by Elsevier Espana. All rights reserved.

  1. [Mucinous papillary cystadenoma of the pancreas].

    PubMed

    Ledezma, G; Salloum, S; de Sulbarán, Y; de Armas, L

    1992-01-01

    The case of a 15-years-old female patient is presented, who referred pain and presence of a mass in the left upper quadrant of the abdomen. Diagnostic imaging showed a 9 cm diameter cystic lesion in the tail of the pancreas which was removed surgically. Histology demonstrated a pancreatic mucinous cystadenoma with borderline biological behaviour. A review of the literature related to cystic neoplasms of the pancreas is realized.

  2. Who needs an artificial pancreas? (?).

    PubMed

    Winikoff, Janet; Drexler, Andrew

    2013-09-01

    The development of a closed-loop "artificial pancreas" would be a welcome advance for both endocrinologists and diabetic patients struggling to attain near normal glycemic control. While great strides in automatically controlling blood sugar in the fasting, sedentary state have been made through complex mathematical modeling, management of blood sugar excursions due to food and exercise have been more problematic. An artificial pancreas is not feasible at this time because of limitations inherent in the currently available technology.

  3. Successful Case of Somatostatin Analog Stopping Gastrointestinal Bleeding, One of the Most Frequent Complications After Simultaneous Pancreas-kidney Transplantation: A Case Report.

    PubMed

    Miyagi, S; Fujio, A; Tokodai, K; Hara, Y; Nakanishi, C; Goto, H; Kamei, T; Kawagishi, N; Ohuchi, N; Satomi, S

    2016-04-01

    Pancreas transplantation has the highest surgical complication rate of all routinely performed organ transplantation procedures. The complications are not only caused by the pancreas itself but also occur due to issues with the transplant recipient. We report the case of a patient who experienced massive gastrointestinal bleeding after simultaneous pancreas-kidney transplantation (SPK), which was stopped successfully using somatostatin analog. The patient was a 45-year-old woman with diabetes mellitus type 1 who underwent SPK with enteric drainage. She had melena 5 days after SPK. At first, we suspected that the melena was caused by the transplanted duodenum because of rejection and ischemic changes. The patient experienced severe bleeding 9 days after SPK. We quickly performed open surgery and inserted an endoscope from the recipient's ileum to investigate the transplanted duodenum. However, no bleeding source was found, including in the transplanted duodenum and the recipient's ileum end. We determined that the bleeding source was the recipient's ascending colon. We attempted to perform endovascular treatment but could not detect the source of the bleeding; therefore, we used somatostatin analog to let the blood vessels shrink and reduce pancreatic output. Thereafter, the function of the transplanted pancreas and kidney gradually recovered, and the recipient was discharged 154 days after SPK. Gastrointestinal bleeding is a lethal complication and has several different causes, such as mucosal rejection, ischemic changes, and exocrine output of the pancreas graft. Somatostatin analog is one of the most acceptable treatments for patients who have gastrointestinal bleeding after SPK. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. The insulin secretion of a minced neonatal rat pancreas cultured in a pancreatic chamber, in response to various insulin secretagogues.

    PubMed

    Araki, Y; Yoshioka, K; Inoue, Y; Nakamura, Y; Nakamura, N; Nakano, K; Yoshida, T; Kondo, M

    1981-02-01

    The minced pancreas of the neonatal rat was cultured for 35 days in a pancreatic chamber which was constructed of a plastic tube and an ultrafiltration membrane. Insulin and amylase secreted from this pancreatic chamber into the culture medium were measured. During the experiment, the concentration of glucose in the culture medium was changed between 5.5 and 16.5 mM at 2-3 day intervals in order to determine the insulin secretory response of the pancreatic tissue. Insulin secretion was markedly increased in response to 16.5 mM glucose. The ratio of insulin secretion to amylase secretion in the culture medium increased with the advance of culture days although secretions of both insulin and amylase decreased individually. On the 7th culture day, short term incubations were performed to test with various insulin secretagogues; obvious insulin release into the incubation medium was observed. These results show that the pancreatic chamber also in vitro secretes insulin rapidly and significantly in response to various stimuli; that by longer culture of a neonatal rat pancreas in this device, insulin secretory cells without exocrine tissue would be obtained without using digestive enzymes; that application of a pancreatic chamber for a pancreatic transplantation may be feasible.

  5. Accumulation of Extracellular Matrix and Developmental Dysregulation in the Pancreas by Transgenic Production of Transforming Growth Factor-β1

    PubMed Central

    Lee, Myung-Shik; Gu, Danling; Feng, Lili; Curriden, Scott; Arnush, Marc; Krahl, Troy; Gurushanthaiah, Deepak; Wilson, Curtis; Loskutoff, David L.; Fox, Howard; Sarvetnick, Nora

    1995-01-01

    Transgenic mice expressing transforming growth factor-β1 (TGF-β1) in the pancreatic β-islet cells directed by human insulin promoter were produced to study in vivo effects of TGF-β1. Fibroblast proliferation and abnormal deposition of extracellular matrix were observed from birth onward, finally replacing almost all the exocrine pancreas. Cellular infiltrates comprising macrophages and neutrophils were also observed. Plasminogen activator inhibitor was induced in the transgenic pancreas as well as fibronectin and laminin, partly explaining accumulation of extracellular matrix. TGF-β1 inhibited proliferation of acinar cells in vivo as evidenced by decreased bromodeoxyuridine incorporation. Development of pancreatic islets was dysregulated, resulting in small islet cell clusters without formation of normal adult islets; however, the overall islet cell mass was not signfifcantly diminished. Additional transgenic lines with less pronounced phenotypes had less expression of TGF-β1 transgene. These findings suggest that TGF-β1 might be a mediator of diseases associated with extracellular matrix deposition such as chronic pancreatitis, and this mouse model will be useful for further analysis of the in vivo effects of TGF-β1, including its potential for immunosuppression. Imagesp43-aFigure 2Figure 3Figure 4Figure 5Figure 6 PMID:7604884

  6. Diabetic Foot Complications Despite Successful Pancreas Transplantation.

    PubMed

    Seo, Dong-Kyo; Lee, Ho Seong; Park, Jungu; Ryu, Chang Hyun; Han, Duck Jong; Seo, Sang Gyo

    2017-06-01

    It is known that successful pancreas transplantation enables patients with diabetes to maintain a normal glucose level without insulin and reduces diabetes-related complications. However, we have little information about the foot-specific morbidity in patients who have undergone successful pancreas transplantation. The purpose of this study was to investigate the prevalence and predisposing factors for foot complications after successful pancreas transplantation. This retrospective study included 218 patients (91 males, 127 females) who had undergone pancreas transplantation for diabetes. The mean age was 40.7 (range, 15-76) years. Diabetes type, transplantation type, body mass index, and diabetes duration before transplantation were confirmed. After pancreas transplantation, the occurrence and duration of foot and ankle complications were assessed. Twenty-two patients (10.1%) had diabetic foot complications. Fifteen patients (6.9%) had diabetic foot ulcer and 7 patients (3.2%) had Charcot arthropathy. Three patients had both diabetic foot ulcer and Charcot arthropathy. Three insufficiency fractures (1.4%) were included. Mean time of complications after transplantation was 18.5 (range, 2-77) months. Creatinine level 1 year after surgery was higher in the complication group rather than the noncomplication group ( P = .02). Complications of the foot and ankle still occurred following pancreas transplantation in patients with diabetes. Level III, comparative study.

  7. Aquaporins in salivary glands and pancreas.

    PubMed

    Delporte, Christine

    2014-05-01

    Salivary glands and pancreas are involved in saliva secretion, pancreatic fluid secretion and insulin secretion. These functions are essential for proper oral, pancreatic and glucose homeostasis. Aquaporins are water-permeable transmembrane protein involved in the physiology of these secretory gland functions. This review gives an overview of the morphology of salivary glands and pancreas, the expression and localization of aquaporins, the secretion roles and mechanisms, the physiological roles of aquaporins, and the role of aquaporins in pathophysiological conditions. Several aquaporins are expressed in salivary glands and pancreas, and some play important physiological roles. Modulation of aquaporin expression and/or trafficking may contribute to the pathogenesis of diseases affecting salivary glands and pancreas glands such as xerostomic conditions, pancreatic insufficiencies and diabetes. Aquaporins are involved in physiological and pathophysiological processes in salivary glands and pancreas. They could represent therapeutic targets for the treatment of diseases affecting the salivary glands and pancreas. This article is part of a Special Issue entitled Aquaporins. © 2013.

  8. Air in the main pancreatic duct: a case of innocent air.

    PubMed

    Kim, Yun Ji; Kim, Hyung Keun; Cho, Young Seok; Kim, Sung Soo; Chae, Hiun Suk; Kim, Seung Kyong; Kim, Eun Sun; Lee, Su Yeon

    2012-09-28

    Air in the main pancreatic duct has been reported only rarely and might be associated with either a spontaneous or a surgically induced alteration of the anatomy of the biliary tract. We report a case of "innocent" air found incidentally in the main pancreatic duct. To our knowledge, this is only the third such case reported. A 54-year-old woman presented with hemoptysis that had lasted for 3 d. She underwent a chest computed tomography scan, which revealed not only focal bronchiectasis in the left lower lobe, but also air in the main pancreatic duct and dilatation of the common bile duct. She was managed conservatively for the hemoptysis and no further problems developed. She had no specific gastrointestinal symptoms and had no history of surgery or medication. Her laboratory parameters were normal. Magnetic resonance cholangiopancreatography also demonstrated air in the main pancreatic duct and a dilated common bile duct (CBD). Duodenoscopy revealed separate biliary and pancreatic orifices with patulous openings and some air bubbles appearing in the pancreatic orifice. Endoscopic retrograde cholangiopancreatography (ERCP) showed the dilated CBD and pancreatic duct with some air bubbles, but no other abnormal lesions. She was discharged with no further problems. Most patients with air in the main pancreatic duct have had a pancreatobiliary disease, or a history of pancreatobiliary disease, pancreatobiliary surgery or sphincterotomy. If the air is innocent, as in our case, ERCP should be performed to evaluate any altered sphincteric function or anatomy such as patulous openings.

  9. Outpatient echocardiography in the evaluation of innocent murmurs in children: utilisation benchmarking.

    PubMed

    Frias, Patricio A; Oster, Matthew; Daley, Patricia A; Boris, Jeffrey R

    2016-03-01

    We sought to benchmark the utilisation of echocardiography in the outpatient evaluation of heart murmurs by evaluating two large paediatric cardiology centres. Although criteria exist for appropriate use of echocardiography, there are no benchmarking data demonstrating its utilisation. We performed a retrospective cohort study of outpatients aged between 0 and 18 years at the Sibley Heart Center Cardiology and the Children's Hospital of Philadelphia Division of Cardiology, given a sole diagnosis of "innocent murmur" from 1 July, 2007 to 31 October, 2010. Using internal claims data, we compared the utilisation of echocardiography according to centre, patient age, and physician years of service. Of 23,114 eligible patients (Sibley Heart Center Cardiology: 12,815, Children's Hospital of Philadelphia Division of Cardiology: 10,299), 43.1% (Sibley Heart Center Cardiology: 45.2%, Children's Hospital of Philadelphia Division of Cardiology: 40.4%; p1-5 years had the lowest utilisation (32.7%). In two large paediatric cardiology practices, the overall utilisation of echocardiography by physicians with a sole diagnosis of innocent murmur was similar. There was significant and similar variability in utilisation by provider at both centres. Although these data serve as initial benchmarking, the variability in utilisation highlights the importance of appropriate use criteria.

  10. Cystic Neoplasms of the Pancreas

    PubMed Central

    Tran Cao, Hop S.; Kellogg, Benjamin; Lowy, Andrew M.; Bouvet, Michael

    2015-01-01

    Whereas pancreatic duct adenocarcinoma (PDA) is a well-studied (but still poorly understood) disease with a dismal prognosis, cystic neoplasms of the pancreas form a more recently recognized group of pancreatic tumors. They are diverse and variable in their pathologic characteristics, clinical course, and outcomes,1–3 although all portend a better overall prognosis than PDA. In recent years, with the improved sensitivity and increasing use of cross-sectional imaging in clinical practice, these lesions are more commonly identified,4 with many being discovered incidentally. Indeed, large radiological series using computed tomography (CT) or magnetic resonance imaging (MRI) have reported detection rates of pancreatic cystic lesions between 1.2% and almost 20%,5,6 approaching the 24.3% prevalence rate in an autopsy series by Kimura and colleagues.7 Although most of these lesions are pseudocysts, a significant portion consist of cystic neoplasms, which are estimated to represent 10% to 15% of all primary pancreatic cystic lesions.8 Given the growing clinical relevance of these tumors, a keen understanding of their natural history and pathophysiology is needed. This article reviews pancreatic cystic neoplasms, with a focus on the challenges encountered in their diagnosis and treatment. PMID:20159515

  11. Comparative evaluation of exocrine muscarinic receptor binding characteristics and inhibition of salivation of solifenacin in mice.

    PubMed

    Oki, Tomomi; Takeuchi, Chihiro; Yamada, Shizuo

    2006-07-01

    Anticholinergic agents such as oxybutynin are clinically useful in the treatment of overactive bladder. However, oral administration of oxybutynin is frequently accompanied by side effects such as dry mouth, and novel bladder-selective anticholinergic agents such as solifenacin and tolterodine are now under development. The aim of the present study was to characterize the suppression of cholinergic salivation and exocrine muscarinic receptor binding of solifenacin on oral administration to mice in comparison with those of oxybutynin. Results showed that both drugs produced a significant increase in K(d) values for specific [N-Methyl-(3)H]scopolamine methyl chloride ([(3)H]NMS) binding in the mouse submaxillary gland, compared with control values. However, this enhancement in K(d) values was significantly smaller with solifenacin than with oxybutynin. Moreover, the inhibitory effect of solifenacin on pilocarpine-induced salivary secretion was significantly weaker than that of oxybutynin. Solifenacin dissociated more readily from muscarinic receptors in the mouse submaxillary gland than oxybutynin. In conclusion, the present study indicates that the weak suppression of cholinergic salivation by solifenacin compared with oxybutynin may be partially attributed to its relatively fast dissociation kinetics from exocrine muscarinic receptors.

  12. Endocytosis of secreted carboxyl ester lipase in a syndrome of diabetes and pancreatic exocrine dysfunction.

    PubMed

    Torsvik, Janniche; Johansson, Bente B; Dalva, Monica; Marie, Michaël; Fjeld, Karianne; Johansson, Stefan; Bjørkøy, Geir; Saraste, Jaakko; Njølstad, Pål R; Molven, Anders

    2014-10-17

    Maturity-onset diabetes of the young, type 8 (MODY8) is characterized by a syndrome of autosomal dominantly inherited diabetes and exocrine pancreatic dysfunction. It is caused by deletion mutations in the last exon of the carboxyl ester lipase (CEL) gene, resulting in a CEL protein with increased tendency to aggregate. In this study we investigated the intracellular distribution of the wild type (WT) and mutant (MUT) CEL proteins in cellular models. We found that both CEL-WT and CEL-MUT were secreted via the endoplasmic reticulum and Golgi compartments. However, their subcellular distributions differed, as only CEL-MUT was observed as an aggregate at the cell surface and inside large cytoplasmic vacuoles. Many of the vacuoles were identified as components of the endosomal system, and after its secretion, the mutant CEL protein was re-internalized, transported to the lysosomes, and degraded. Internalization of CEL-MUT also led to reduced viability of pancreatic acinar and beta cells. These findings may have implications for the understanding of how the acinar-specific CEL-MUT protein causes both exocrine and endocrine pancreatic disease.

  13. A good breath of oxygen for beta-like cells obtained from porcine exocrine pancreatic tissue.

    PubMed

    Gioviale, M C; Damiano, G; Cacciabaudo, F; Palumbo, V D; Bellavia, M; Cassata, G; Spinelli, G; Buscemi, G; Lo Monte, A I

    2011-05-01

    Ischemia is the most important factor that affects organ survival during harvesting. The two-layer method (TLM) is one of several cold storage solutions that seeks to preserve organs and cells avoiding in vivo and in vitro ischemia. We compared the retrieval of beta-like elements from exocrine pancreatic cells using TLM versus University of Wisconsin (UW) solutions. For this purpose pancreata laparoscopically harvested from 20 female pigs were preserved in UW solution or TLM before digestion. The resulting exocrine cells were divided into 2 groups: the first was cultured in a designed medium to allow differentiation into beta-like cells and the second was cryopreserved before the differentiation process at -196 °C for 8 weeks before culture in the same medium. The results revealed that TLM was better than UW as a preservation solution in terms of beta-cell viability and insulin secretion. We suggest that the use of TLM solution allows one to obtain less damaged cells for research purposes.

  14. Preserved exocrine function in patients with acute cholera and acute non-cholera diarrhoea.

    PubMed

    Molla, A; Gyr, K; Molla, A M; Bardhan, P; Patra, F C

    1986-10-01

    Exocrine pancreatic function was assessed by means of the Lundh test in 14 patients with acute cholera and 18 patients with acute infectious non-cholera diarrhoea within the first 24 h of their admission. Mean tryptic activity amounted to 39.8 +/- 4.8 microEq/min/ml in the cholera group and to 64.4 +/- 11.0 microEq/min/ml in the non-cholera group. None of these patients shared a value below the lower limit of normal. In fact, the mean tryptic activity per 2 h was significantly higher than that reported previously in a control group from the Bengal area. It is therefore concluded that the exocrine pancreatic function is preserved and responds to food stimulation in various types of acute infectious diarrhoea, including cholera. These findings provide the pathophysiological background for the recent observation that oral rehydration solutions containing high-molecular-weight nutrients such as rice powder are at least as efficient or even more potent than the WHO-recommended glucose-electrolyte formula in acute diarrhoea.

  15. Role of Calcium and PKC in Salivary Mucous Cell Exocrine Secretion

    PubMed Central

    Culp, D.J.; Zhang, Z.; Evans, R.L.

    2011-01-01

    Fluid and exocrine secretion of mucins by salivary mucous glands is regulated predominantly by parasympathetic activation of muscarinic receptors. A direct role for subsequent putative signaling steps, phospholipase C (PLC), increased intracellular calcium ([Ca2+]i), and isoforms of protein kinase C (PKC) in mediating muscarinic exocrine secretion has not been elucidated, and these are potential therapeutic targets to enhance mucin secretion in hyposalivary patients. We found that muscarinic-induced mucin secretion by rat sublingual tubulo-acini was dependent upon PLC activation and the subsequent increase in [Ca2+]i, and further identified a transient PKC-independent component of secretion dependent upon Ca2+ release from intracellular stores, whereas sustained secretion required entry of extracellular Ca2+. Interactions among carbachol, PKC inhibitors, phorbol 12-myristate 13-acetate, and thapsigargin to modulate [Ca2+]i implicated conventional PKC isoforms in mediating sustained secretion. With increasing times during carbachol perfusion of glands, in situ, PKC-α redistributed across glandular membrane compartments and underwent a rapid and persistent accumulation near the luminal borders of mucous cells. PKC-β1 displayed transient localization near luminal borders, whereas the novel PKCs, PKC-δ or PKC-ϵ, displayed little or no redistribution in mucous cells. Collective results implicate synergistic interactions between diacylglycerol (DAG) and increasing [Ca2+]i levels to activate cPKCs in mediating sustained muscarinic-induced secretion. PMID:21933938

  16. Potential for Screening for Pancreatic Exocrine Insufficiency Using the Fecal Elastase-1 Test.

    PubMed

    Domínguez-Muñoz, J Enrique; D Hardt, Philip; Lerch, Markus M; Löhr, Matthias J

    2017-03-17

    The early diagnosis of pancreatic exocrine insufficiency (PEI) is hindered because many of the functional diagnostic techniques used are expensive and require specialized facilities, which prevent their widespread availability. We have reviewed current evidence in order to compare the utility of these functional diagnostic techniques with the fecal elastase-1 (FE-1) test in the following three scenarios: screening for PEI in patients presenting with symptoms suggestive of pancreatic disease, such as abdominal pain or diarrhea; determining the presence of PEI in patients with an established diagnosis of pancreatic disease, such as chronic pancreatitis or cystic fibrosis; determining exocrine status in disorders not commonly tested for PEI, but which have a known association with this disorder. Evidence suggests the FE-1 test is reliable for the evaluation of pancreatic function in many pancreatic and non-pancreatic disorders. It is non-invasive, is less time-consuming, and is unaffected by pancreatic enzyme replacement therapy. Although it cannot be considered the gold-standard method for the functional diagnosis of PEI, the advantages of the FE-1 test make it a very appropriate test for screening patients who may be at risk of this disorder.

  17. Targeted ablation of beta cells in the embryonic zebrafish pancreas using E.coli nitroreductase

    PubMed Central

    Pisharath, Harshan; Rhee, Jerry M.; Swanson, Michelle A.; Leach, Steven D.; Parsons, Michael J.

    2007-01-01

    In order to generate a zebrafish model of β cell regeneration, we have expressed an E.coli gene called nfsB in the β cells of embryonic zebrafish. This bacterial gene encodes a nitroreductase (NTR) enzyme, which can convert prodrugs such as metronidazole (Met) to cytotoxins. By fusing nfsB to mCherry, we can simultaneously render β cells susceptible to prodrug and visualize Met dependent cell ablation. We show that the neighboring α and δ cells are unaffected by prodrug treatment and that ablation is β cell specific. Following drug removal and 36hrs of recovery, β cells regenerate. Using ptf1a morphants, it is clear that this β cell recovery occurs independently of the presence of the exocrine pancreas. Also, by using photoconvertible Kaede to cell lineage trace and BrdU incorporation to label proliferation, we investigate mechanisms for β regeneration. Therefore, we have developed a unique resource for the study of β cell regeneration in a living vertebrate organism, which will provide the opportunity to conduct large-scale screens for pharmacological and genetic modifiers of β cell regeneration. PMID:17223324

  18. Pluripotency of adult stem cells derived from human and rat pancreas

    NASA Astrophysics Data System (ADS)

    Kruse, C.; Birth, M.; Rohwedel, J.; Assmuth, K.; Goepel, A.; Wedel, T.

    Adult stem cells are undifferentiated cells found within fully developed tissues or organs of an adult individuum. Until recently, these cells have been considered to bear less self-renewal ability and differentiation potency compared to embryonic stem cells. In recent studies an undifferentiated cell type was found in primary cultures of isolated acini from exocrine pancreas termed pancreatic stellate cells. Here we show that pancreatic stellate-like cells have the capacity of extended self-renewal and are able to differentiate spontaneously into cell types of all three germ layers expressing markers for smooth muscle cells, neurons, glial cells, epithelial cells, chondrocytes and secretory cells (insulin, amylase). Differentiation and subsequent formation of three-dimensional cellular aggregates (organoid bodies) were induced by merely culturing pancreatic stellate-like cells in hanging drops. These cells were developed into stable, long-term, in vitro cultures of both primary undifferentiated cell lines as well as organoid cultures. Thus, evidence is given that cell lineages of endodermal, mesodermal, and ectodermal origin arise spontaneously from a single adult undifferentiated cell type. Based on the present findings it is assumed that pancreatic stellate-like cells are a new class of lineage uncommitted pluripotent adult stem cells with a remarkable self-renewal ability and differentiation potency. The data emphasize the versatility of adult stem cells and may lead to a reappraisal of their use for the treatment of inherited disorders or acquired degenerative diseases.

  19. Solid Pseudopapillary Neoplasms of the Pancreas: A Surgical and Genetic Enigma.

    PubMed

    Naar, Leon; Spanomichou, Despoina-Amalia; Mastoraki, Aikaterini; Smyrniotis, Vassilios; Arkadopoulos, Nikolaos

    2017-03-01

    Solid pseudopapillary neoplasms of the pancreas are rare tumors accounting for 1-2% of pancreatic exocrine neoplasms. This entity was first described by Dr. Frantz in 1959 and was defined by the World Health Organization in 1996 as "solid pseudopapillary tumor." It is most often a benign neoplasm, but 10-15% of the cases are malignant. Over the past decades, the incidence of this tumor is increasing. However, many surgeons are still unfamiliar with this neoplasm and its unique characteristics, which can lead to pitfalls in the diagnosis and treatment. The correct diagnosis of SPNP is of utmost importance since it has a low malignant potential and with the appropriate treatment, patients have a long life expectancy. There are many genetic alterations, involving various signaling pathways that have been associated with SPNP and are very important in diagnosing the tumor. The cornerstone of SPNP treatment includes surgical excision of the tumor, preserving as much pancreatic tissue as possible. We review the information in the literature regarding more organ-preserving techniques and possible clinical features that might indicate a malignant potential, thus demanding a more radical intraoperative excision.

  20. Melatonin, endocrine pancreas and diabetes.

    PubMed

    Peschke, Elmar

    2008-01-01

    Melatonin influences insulin secretion both in vivo and in vitro. (i) The effects are MT(1)-and MT(2)-receptor-mediated. (ii) They are specific, high-affinity, pertussis-toxin-sensitive, G(i)-protein-coupled, leading to inhibition of the cAMP-pathway and decrease of insulin release. [Correction added after online publication 4 December 2007: in the preceding sentence, 'increase of insulin release' was changed to 'decrease of insulin release'.] Furthermore, melatonin inhibits the cGMP-pathway, possibly mediated by MT(2) receptors. In this way, melatonin likely inhibits insulin release. A third system, the IP(3)-pathway, is mediated by G(q)-proteins, phospholipase C and IP(3), which mobilize Ca(2+) from intracellular stores, with a resultant increase in insulin. (iii) Insulin secretion in vivo, as well as from isolated islets, exhibits a circadian rhythm. This rhythm, which is apparently generated within the islets, is influenced by melatonin, which induces a phase shift in insulin secretion. (iv) Observation of the circadian expression of clock genes in the pancreas could possibly be an indication of the generation of circadian rhythms in the pancreatic islets themselves. (v) Melatonin influences diabetes and associated metabolic disturbances. The diabetogens, alloxan and streptozotocin, lead to selective destruction of beta-cells through their accumulation in these cells, where they induce the generation of ROS. Beta-cells are very susceptible to oxidative stress because they possess only low-antioxidative capacity. Results suggest that melatonin in pharmacological doses provides protection against ROS. (vi) Finally, melatonin levels in plasma, as well as the arylalkylamine-N-acetyltransferase (AANAT) activity, are lower in diabetic than in nondiabetic rats and humans. In contrast, in the pineal gland, the AANAT mRNA is increased and the insulin receptor mRNA is decreased, which indicates a close interrelationship between insulin and melatonin.

  1. The (Un)reliability of Alibi Corroborators: Failure to Recognize Faces of Briefly Encountered Strangers Puts Innocent Suspects at Risk.

    PubMed

    Charman, Steve D; Reyes, Andrea; Villalba, Daniella K; Evans, Jacqueline R

    2016-10-19

    Some innocent suspects rely on the memory of strangers to corroborate their alibis. However, no research has examined whether such potential alibi corroborators can accurately recognize an innocent suspect with whom they previously interacted. We developed a novel alibi corroboration paradigm in which undergraduate students (representing innocent suspects who would later provide an alibi) interacted with naïve university employees (representing potential alibi corroborators). Each student briefly interacted with a different naïve university employee (n = 60), and were also each yoked to a different employee with whom they did not interact (n = 60). Employees were presented 24 hours later with either a single photograph of the student or a six-person array containing a photograph of the student and were asked if they recognized anyone. The majority of employees failed to make a correct recognition of the student. False recognitions, however, were rare. Students exhibited overconfidence that they would be recognized. Findings imply that innocent suspects who rely on strangers to corroborate their alibis may be at risk. Copyright © 2016 John Wiley & Sons, Ltd.

  2. Pancreas graft survival in simultaneous pancreas-kidney versus pancreas-after-kidney and pancreas alone transplantations: a single institution experience.

    PubMed

    Montiel-Casado, M C; Pérez-Daga, J A; Aranda-Narváez, J M; Fernández-Burgos, I; Sánchez-Pérez, B; León-Díaz, F J; Cabello-Díaz, M; Rodríguez-Burgos, D; Hernández-Marrero, D; Santoyo-Santoyo, J

    2013-01-01

    Pancreas transplantation offers excellent outcomes today in patients who have type-1 diabetes mellitus (DM) with difficult control in terms of increasing patient and pancreatic graft survival. Different factors in donors, recipients, and the perioperative period have been associated with long-term graft survival. The aim of this study was to compare pancreatic graft survival in simultaneous pancreas-kidney transplantation (SPK) and the other two modalities, pancreas-alone and pancreas-after-kidney transplantation (non-SPK), at our institution. This retrospective cohort study included 63 pancreas transplantation patients from January 2007 to May 2012 at our institution. The patients were divided into two groups: SPK and non-SPK transplantations. We excluded those patients who had transplants with vascular graft loss. The primary endpoint was 1-year and overall graft survival with consideration of multiple relevant variables. Non-parametric tests were calculated with the statistical package SPSS 20 (SPSS INC, Chicago, IL). The 1-year and overall graft survival in this period was 87.3% and 82.5%, respectively. The median follow-up was 963 days. The causes of graft loss were vascular (64%) and immunologic (34%). Finally, we included 56 pancreas transplantations, 46 (82%) were SPK and 10 (18%) non-SPK. The donor and recipient characteristics were similar in both groups, except for the duration of DM (SPK 22 years vs. non-SPK 29 years) and recipient body mass index (SPK 23 vs. non-SPK 28); P = .042 and P = .003, respectively. The cold ischemia time was 563 minutes (standard deviation, 145). Bivariate analysis showed that long-term graft loss was only influenced by matching for gender (P = .023). Using the Kaplan-Meier method, the pancreas graft survival was better in SPK than in non-SPK transplants (log rank .038). Patients who receive pancreas-alone or pancreas-after-kidney grafts have shorter long-term graft survival. Multiple strategies should be applied to improve

  3. Progress and challenges of the bioartificial pancreas

    NASA Astrophysics Data System (ADS)

    Hwang, Patrick T. J.; Shah, Dishant K.; Garcia, Jacob A.; Bae, Chae Yun; Lim, Dong-Jin; Huiszoon, Ryan C.; Alexander, Grant C.; Jun, Ho-Wook

    2016-11-01

    Pancreatic islet transplantation has been validated as a treatment for type 1 diabetes since it maintains consistent and sustained type 1 diabetes reversal. However, one of the major challenges in pancreatic islet transplantation is the body's natural immune response to the implanted islets. Immunosuppressive drug treatment is the most popular immunomodulatory approach for islet graft survival. However, administration of immunosuppressive drugs gives rise to negative side effects, and long-term effects are not clearly understood. A bioartificial pancreas is a therapeutic approach to enable pancreatic islet transplantation without or with minimal immune suppression. The bioartificial pancreas encapsulates the pancreatic islets in a semi-permeable environment which protects islets from the body's immune responses, while allowing the permeation of insulin, oxygen, nutrients, and waste. Many groups have developed various types of the bioartificial pancreas and tested their efficacy in animal models. However, the clinical application of the bioartificial pancreas still requires further investigation. In this review, we discuss several types of bioartificial pancreases and address their advantages and limitations. We also discuss recent advances in bioartificial pancreas applications with microfluidic or micropatterning technology.

  4. Exocrine and endocrine functional reserve in the course of chronic pancreatitis as studied by maximal stimulation tests.

    PubMed

    Cavallini, G; Bovo, P; Zamboni, M; Bosello, O; Filippini, M; Riela, A; Brocco, G; Rossi, L; Pelle, C; Chiavenato, A

    1992-01-01

    Thirty patients suffering from chronic alcoholic pancreatitis (18 calcified) were entered into a study of exocrine and endocrine pancreatic function based on two maximal stimulation tests, namely the secretin-cerulein test and the glucagon test with serum assays of C peptide. The glucagon test was also performed in 19 control subjects. In addition, 10 chronic pancreatitis patients and nine controls were subjected to an oral glucose tolerance test (OGTT) with serum insulin determinations. C peptide basal values were decreased only in patients with severe pancreatic exocrine insufficiency (P less than 0.001), while delta C peptide values were also reduced in patients with moderate exocrine insufficiency (P less than 0.001). Lipase output correlated very well with delta C peptide values (P less than 0.001). While serum insulin levels during OGTT and C peptide basal values showed no significant differences between the chronic pancreatitis and control groups, delta C peptide values were significantly reduced in chronic pancreatitis patients (P less than 0.02). Both endocrine and exocrine function are impaired in chronic pancreatitis, as demonstrated by maximal tests, even in early stages of the disease.

  5. QUILT-2.014: Gemcitabine and AMG 479 in Metastatic Adenocarcinoma of the Pancreas

    ClinicalTrials.gov

    2016-10-26

    Adenocarcinoma of the Pancreas; Advanced Solid Tumors; Cancer; Cancer of Pancreas; Cancer of the Pancreas; Metastases; Metastatic Cancer; Metastatic Pancreatic Cancer; Pancreas Cancer; Pancreatic Cancer; Bone Metastases; Endocrine Cancer; Oncology; Oncology Patients; Solid Tumors; Advanced Malignancy

  6. Multipotent pancreas progenitors: Inconclusive but pivotal topic

    PubMed Central

    Jiang, Fang-Xu; Morahan, Grant

    2015-01-01

    The establishment of multipotent pancreas progenitors (MPP) should have a significant impact not only on the ontology of the pancreas, but also for the translational research of glucose-responding endocrine β-cells. Deficiency of the latter may lead to the pandemic type 1 or type 2 diabetes mellitus, a metabolic disorder. An ideal treatment of which would potentially be the replacement of destroyed or failed β-cells, by restoring function of endogenous pancreatic endocrine cells or by transplantation of donor islets or in vitro generated insulin-secreting cells. Thus, considerable research efforts have been devoted to identify MPP candidates in the pre- and post-natal pancreas for the endogenous neogenesis or regeneration of endocrine insulin-secreting cells. In order to advance this inconclusive but critical field, we here review the emerging concepts, recent literature and newest developments of potential MPP and propose measures that would assist its forward progression. PMID:26730269

  7. Conservative Pancreas Graft Preservation at the Extreme

    PubMed Central

    Laurence, Jerome Martin; Sapisochin, Gonzalo; Selzner, Markus; Norgate, Andrea; Kumar, Deepali; McGilvary, Ian D.; Preig, Paul D.; Schiff, Jeffrey; Cattral, Mark S.

    2016-01-01

    Because of the value some patients place in remaining insulin-independent after pancreas transplantation, they may be reluctant to undergo graft pancreatectomy, even in the face of extreme complications, such as graft thrombosis and duodenal segment leak. Partly, for this reason, a variety of complex salvage techniques have been described to save the graft in such circumstances. We report a case of a series of extreme complications related to a leak from the duodenal segment after a simultaneous pancreas and kidney transplant. These included infected thrombosis of the inferior vena cava associated with a graft venous thrombosis and a retroperitoneal fistula. The patient retained graft function with insulin independence and repeatedly declined graft pancreatectomy against the advice of the transplant team. Conservative treatment with percutaneous drainage, antibiotics, and anticoagulation was eventually successful. This outcome is unique in our experience and may be instructive to teams caring for pancreas transplant recipients. PMID:27500244

  8. Bringing the artificial pancreas home: telemedicine aspects.

    PubMed

    Lanzola, Giordano; Capozzi, Davide; Serina, Nadia; Magni, Lalo; Bellazzi, Riccardo

    2011-11-01

    The design and implementation of telemedicine systems able to support the artificial pancreas need careful choices to cope with technological requirements while preserving performance and decision support capabilities. This article addresses the issue of designing a general architecture for the telemedicine components of an artificial pancreas and illustrates a viable solution that is able to deal with different use cases and is amenable to support mobile-health implementations. The goal is to enforce interoperability among the components of the architecture and guarantee maximum flexibility for the ensuing implementations. Thus, the design stresses modularity and separation of concerns along with adoption of clearly defined protocols for interconnecting the necessary components. This accounts for the implementation of integrated telemedicine systems suitable as short-term monitoring devices for supporting validation of closed-loop algorithms as well as devices meant to provide a lifelong tighter control on the patient state once the artificial pancreas has become the preferred treatment for patients with diabetes.

  9. JSUM ultrasound elastography practice guidelines: pancreas.

    PubMed

    Hirooka, Yoshiki; Kuwahara, Takamichi; Irisawa, Atsushi; Itokawa, Fumihide; Uchida, Hiroki; Sasahira, Naoki; Kawada, Natsuko; Itoh, Yuya; Shiina, Tsuyoshi

    2015-04-01

    Ultrasound elastography is a relatively new diagnostic technique for measuring the elasticity (hardness) of tissue. Eleven years have passed since the debut of elastography. Various elastography devices are currently being marketed by manufacturers under different names. Pancreatic elastography can be used not only with transabdominal ultrasonography but also with endoscopic ultrasonography, but some types of elastography are difficult to perform for the pancreas. These guidelines aim to classify the various types of elastography into two major categories depending on the differences in the physical quantity (strain, shear wave), and to present the evidence for pancreatic elastography and how to use pancreatic elastography in the present day. But the number of reports on ultrasound elastography for the pancreas is still small, and there are no reports on some elastography devices for the pancreas. Therefore, these guidelines do not recommend methods of imaging and analysis by elastography device.

  10. Intraductal Oncocytic Papillary Neoplasms of the Pancreas.

    PubMed

    Kallen, Michael E; Naini, Bita V

    2016-09-01

    Intraductal oncocytic papillary neoplasms (IOPNs) are cystic neoplasms with intraductal growth and complex papillae composed of oncocytic cells. IOPNs have been reported both in the pancreas and biliary tree, and are most likely closely related in these 2 locations. In the pancreas, these rare tumors are now considered 1 of the 4 histologic subtypes of intraductal papillary mucinous neoplasm (IPMN). Significant differences in histology, immunophenotype, and molecular genetics have been reported between IOPNs and other IPMN subtypes. However, there are limited data regarding the clinical behavior and prognosis of IOPNs in comparison to other subtypes of IPMN. We review features of pancreatic IOPNs and discuss the differential diagnosis of other intraductal lesions in the pancreas.

  11. For Inflamed Pancreas, Eating Right Away May Be Best Medicine

    MedlinePlus

    ... medlineplus.gov/news/fullstory_165624.html For Inflamed Pancreas, Eating Right Away May Be Best Medicine Contrary ... people hospitalized for pancreatitis. This is when the pancreas becomes inflamed, causing pain and swelling in the ...

  12. Fetal microchimeric cells in autoimmune thyroid diseases: harmful, beneficial or innocent for the thyroid gland?

    PubMed

    Lepez, Trees; Vandewoestyne, Mado; Deforce, Dieter

    2013-01-01

    Autoimmune thyroid diseases (AITD) show a female predominance, with an increased incidence in the years following parturition. Fetal microchimerism has been suggested to play a role in the pathogenesis of AITD. However, only the presence of fetal microchimeric cells in blood and in the thyroid gland of these patients has been proven, but not an actual active role in AITD. Is fetal microchimerism harmful for the thyroid gland by initiating a Graft versus Host reaction (GvHR) or being the target of a Host versus Graft reaction (HvGR)? Is fetal microchimerism beneficial for the thyroid gland by being a part of tissue repair or are fetal cells just innocent bystanders in the process of autoimmunity? This review explores every hypothesis concerning the role of fetal microchimerism in AITD.

  13. Remote effect of kidney ischemia-reperfusion injury on pancreas: role of oxidative stress and mitochondrial apoptosis

    PubMed Central

    Abogresha, Noha M.; Abdelaziz, Eman Z.; Khalil, Waleed F.

    2015-01-01

    Introduction Recent studies have demonstrated remote effects of renal ischemia/reperfusion (IR) injury on some organs such as brain, liver, and lungs. Oxidative stress is reported to be the cornerstone in such ischemic conditions. Associated apoptosis is also reported in remote lung, liver and myocardial injury after acute kidney injury. So, we postulated that renal IR may affect the pancreas by its remote effect. Oxidative stress and mitochondrial mediated apoptosis may play a crucial role in this injury. We investigated the effects of kidney IR on pancreatic exocrine and endocrine functions, antioxidant enzyme activity, and apoptosis. Material and methods The protective effect of vitamin C was also investigated. The animals were submitted to non-traumatic bilateral renal IR, sham operation or treatment with vitamin C after IR. Rats were sacrificed on the 1st, 3rd, and 7th days of the experiment to evaluate the parameters of oxidative stress (catalase, lipid peroxidase, reduced glutathione and superoxide dismutase), pancreatic endocrine and exocrine function (amylase, insulin and fasting blood glucose), renal functions (serum creatinine and blood urea nitrogen), cellular injury and apoptotic markers (Bcl-2, Bax and caspase-3). Results Kidney I/R significantly increased the renal and pancreatic functions at 1, 3 and 7 days, while fasting insulin was significantly increased at day 3 after ischemia. Moreover, I/R significantly increased the studied oxidative stress markers and decreased the antioxidant capacity in pancreatic tissues. In addition, renal I/R induced numerous histopatological lesions in pancreatic tissues and increased the apoptosis-related genes. Treating the rats with vitamin C (100 mg/kg) significantly restored the renal and pancreatic functions, improved the pancreatic antioxidant capacity and protected the pancreatic tissues from apoptotic necrosis. Conclusions The results suggested that bilateral renal ischemia for 45 min caused significant

  14. Circumportal pancreas with retroportal main pancreatic duct.

    PubMed

    Hashimoto, Yasushi; Ross, Andrew S; Traverso, L William

    2009-08-01

    There have been 6 cases of circumportal pancreas reported, and 2 of them had the main pancreatic duct in a retroportal dorsal portion. This extremely uncommon anomaly is asymptomatic and therefore incidentally discovered. For the surgeon, it is important to discover this during pancreatic resection so the pancreatic duct can be closed and fistula is avoided. We describe the third case where a circumportal pancreas had its main pancreatic duct passing under the portal vein. The duct was identified and ligated. A fistula did not occur.

  15. Torsion of wandering spleen and distal pancreas

    SciTech Connect

    Sheflin, J.R.; Lee, C.M.; Kretchmar, K.A.

    1984-01-01

    Wandering spleen is the term applied to the condition in which a long pedicle allows the spleen to lie in an abnormal location. Torsion of a wandering spleen is an unusual cause of an acute abdomen and is rarely diagnosed preoperatively. Associated torsion of the distal pancreas is even more uncommon. The authors describe a patient with torsion of a wandering spleen and distal pancreas, who was correctly diagnosed, and define the merits of the imaging methods used. The initial examination should be /sup 99//sup m/Tc-sulfur colloid liner-spleen scanning.

  16. Hyperammonaemia due to cobalamin malabsorption in a cat with exocrine pancreatic insufficiency.

    PubMed

    Watanabe, Takayuki; Hoshi, Katsuichiro; Zhang, Chunhua; Ishida, Yuzuru; Sakata, Ikuo

    2012-12-01

    A 10-year-old domestic shorthair cat showed anorexia, lethargy and ptyalism with hyperammonaemia. Portosystemic shunts were not identified by computed tomography angiography. Biopsy results revealed mild interstinal nephritis and no lesion in the liver. Analysis of urine revealed the presence of a high methylmalonic acid (MMA) concentration. Serum cobalamin (vitamin B(12)) and serum feline trypsin-like immunoreactivity levels were also markedly low. The cat was diagnosed as having exocrine pancreatic insufficiency (EPI). After 5 weeks of parenteral cobalamin supplementation, serum cobalamin concentration had increased and urinary MMA concentration had decreased. This case suggests that hyperammonaemia may be caused by accumulation of MMA due to cobalamin malabsorption secondary to feline EPI.

  17. Rat parotid gland amylase: evidence for alterations in an exocrine protein with increased age.

    PubMed

    Baum, B J; Levine, R L; Kuyatt, B L; Sogin, D B

    1982-05-01

    The content of alpha-amylase, the major exocrine secretory protein from rat parotid glands, was studied in young adult and aged rat tissue. alpha-Amylase protein was determined with an enzyme-linked immunosorbent assay. This employed antisera, produced against alpha-amylase purified from young adult rats, but which recognized and precipitated alpha-amylase enzyme activity equally well from both age groups. The parotid gland content of alpha-amylase was reduced about 50% in aged rats. Furthermore, the percentage of total gland protein which was alpha-amylase was decreased about 40% in aged animals. The data suggest that a somewhat specific alteration in alpha-amylase production (synthesis and/or degradation) occurs in parotid glands from aged rats. In addition, alpha-amylase functional activity was followed. The specific enzyme activity (U amylase activity per mg immunoreactive amylase) was about 35% higher in extracts from aged rat parotid glands compared to that of young adult glands.

  18. Retrieval of the pancreas allograft for whole-organ transplantation.

    PubMed

    Fridell, Jonathan A; Powelson, John A; Kubal, Chandrashekhar A; Burke, George W; Sageshima, Junichiro; Rogers, Jeffrey; Stratta, Robert J

    2014-12-01

    Proper pancreas retrieval during multi-organ recovery is one of the cornerstones of technically successful whole-organ pancreas transplantation. With evolving surgical approaches for organ retrieval and implantation, it has become standard to procure the pancreas in conjunction with other abdominal organs without compromising either vasculature, graft quality, or transplant outcomes. This review summarizes the major steps required for proper whole-organ retrieval of the pancreas allograft with suggestions and tips whenever alternative approaches are available.

  19. Exocrine glands of Lepeophtheirus salmonis (Copepoda: Caligidae): Distribution, developmental appearance, and site of secretion.

    PubMed

    Øvergård, Aina-Cathrine; Hamre, Lars A; Harasimczuk, Ewa; Dalvin, Sussie; Nilsen, Frank; Grotmol, Sindre

    2016-12-01

    Exocrine glands of blood-feeding parasitic copepods are believed to be important in host immune response modulation and inhibition of host blood coagulation, but also in the production of substances for integument lubrication and antifouling. In this study, we aimed to characterize the distribution of different types of salmon louse (Lepeophtheirus salmonis) exocrine glands and their site of secretion. The developmental appearance of each gland type was mapped and genes specifically expressed by glands were identified. Three types of tegumental (teg 1-3) glands and one labial gland type were found. The first glands to appear during development were teg 1 and teg 2 glands. They have ducts extending both dorsally and ventrally suggested to be important in lubricating the integument. Teg 1 glands were found to express two astacin metallopeptidases and a gene with fibronectin II domains, while teg 2 glands express a heme peroxidase. The labial glands were first identified in planktonic copepodids, with reservoirs that allows for storage of glandular products. The last gland type to appear during development was named teg 3 and was not seen before the preadult I stage when the lice become more virulent. Teg 3 glands have ducts ending ventrally at the host-parasite contact area, and may secrete substances important for the salmon lice virulence. Salmon lice teg 3 and labial glands are thus likely to be especially important in the host-parasite interaction. Proteins secreted from the salmon louse glands to its salmonid host skin or blood represents a potential interface where the host immune system can meet and elicit effective responses to sea lice antigens. The present study thus represents a fundamental basis for further functional studies and identification of possible vaccine candidates. J. Morphol. 277:1616-1630, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  20. Yarrowia lipolytica Lipase 2 Is Stable and Highly Active in Test Meals and Increases Fat Absorption in an Animal Model of Pancreatic Exocrine Insufficiency.

    PubMed

    Aloulou, Ahmed; Schué, Mathieu; Puccinelli, Delphine; Milano, Stéphane; Delchambre, Chantal; Leblond, Yves; Laugier, René; Carrière, Frédéric

    2015-12-01

    Pancreatic exocrine insufficiency (PEI) reduces pancreatic secretion of digestive enzymes, including lipases. Oral pancreatic enzyme replacement therapy (PERT) with pancreatin produces unsatisfactory results. The lipase 2 produced by the yeast Yarrowia lipolytica (YLLIP2; GenBank: AJ012632) might be used in PERT. We investigated its ability to digest triglycerides in a test meal and its efficacy in reducing fecal fat in an animal model of PEI. YLLIP2 was produced by genetically engineered Y lipolytica and purified from culture media. YLLIP2 or other gastric (LIPF) and pancreatic (PNLIPD) lipases were added to a meal paste containing dietary triglycerides, at a range of pH values (pH 2-7), with and without pepsin or human bile and incubated at 37°C. We collected samples at various time points and measured lipase activities and stabilities. To create an animal model of PEI, steatorrhea was induced by embolization of the exocrine pancreas gland and pancreatic duct ligation in minipigs. The animals were given YLLIP2 (1, 4, 8, 40, or 80 mg/d) or pancreatin (100,000 US Pharmacopeia lipase units/d, controls) for 9 days. We then collected stool samples, measured fat levels, and calculated coefficient of fat absorption (CFA) values. YLLIP2 was highly stable and poorly degraded by pepsin, and had the highest activity of all lipases tested on meal triglyceride at pH 4-7 (pH 6 with bile: 94 ± 34 U/mg; pH 4 without bile: 43 ± 13 U/mg). Only gastric lipase was active and stable at pH 3, whereas YLLIP2 was sensitive to pepsin hydrolysis after pH inactivation. From in vitro test meal experiments, the lipase activity of YLLIP2 (10 mg) was estimated to be equivalent to that of pancreatin (1200 mg; 100,000 US Pharmacopeia units) at pH 6. In PEI minipigs, CFA values increased from 60.1% ± 9.3% before surgery to 90.5% ± 3.2% after administration of 1200 mg pancreatin (P < .05); CFA values increased to a range of 84.6% ± 3.0% to 90.0% ± 3.8% after administration of 4-80 mg YLLIP

  1. Wandering spleen with volvulus of pancreas.

    PubMed

    Karaosmanoglu, Ali Devrim; Onur, Mehmet Ruhi; Karcaaltıncaba, Musturay

    2015-07-01

    Abnormal location of the spleen, which is called wandering spleen, results from laxity or absence of the splenic pedicle. In the presence of an elongated splenic pedicle, torsion of the spleen or neighboring organs may occur, which results in acute or chronic abdominal pain. In this case report, we present imaging findings of a wandering spleen that manifested with volvulus of the pancreas.

  2. Vascular development in the vertebrate pancreas.

    PubMed

    Azizoglu, D Berfin; Chong, Diana C; Villasenor, Alethia; Magenheim, Judith; Barry, David M; Lee, Simon; Marty-Santos, Leilani; Fu, Stephen; Dor, Yuval; Cleaver, Ondine

    2016-12-01

    The vertebrate pancreas is comprised of a highly branched tubular epithelium, which is intimately associated with an extensive and specialized vasculature. While we know a great deal about basic vascular anatomy of the adult pancreas, as well as islet capillaries, surprisingly little is known about the ontogeny of its blood vessels. Here, we analyze development of the pancreatic vasculature in the mouse embryo. We show that pancreatic epithelial branches intercalate with the fine capillary plexus of the surrounding pancreatic mesenchyme. Endothelial cells (ECs) within this mesenchyme are heterogeneous from the onset of organogenesis. Pancreatic arteries take shape before veins, in a manner analogous to early embryonic vessels. The main central artery forms during mid-gestation, as a result of vessel coalescence and remodeling of a vascular plexus. In addition, we show that vessels in the forming pancreas display a predictable architecture that is dependent on VEGF signaling. Over-expression of VEGF disrupts vascular patterning and arteriovenous differentiation within the developing pancreas. This study constitutes a first-time in-depth cellular and molecular characterization of pancreatic blood vessels, as they coordinately grow along with the pancreatic epithelium. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. [Pancreas divisum: endoscopic management. Case report].

    PubMed

    Martínez, Henry; Espinoza, Miguel; Huaman, César; Monge, Eduardo; Salazar, Sonia; Tapia, Abel

    2002-01-01

    This is a case report of a 19 year-old woman, with an acute recurrent pancreatitis diagnose, and pancreas divisum as anatomic alteration. An extensive evaluation including specialized labs, ERCP was done. The diagnosis is suspected during ERCP and confirmed by minor papilla injection. Treatment is directed towards relieving outflow obstruction at the level of the minor papilla, with successful results.

  4. Twelve-Month Pancreas Graft Function Significantly Influences Survival Following Simultaneous Pancreas-Kidney Transplantation

    PubMed Central

    Weiss, Andrew S.; Smits, Gerard; Wiseman, Alexander C.

    2009-01-01

    Background and objectives: Simultaneous pancreas-kidney transplantation (SPK) is regarded as the treatment of choice for type 1 diabetes (T1DM) and kidney dysfunction, despite the morbidity associated with pancreas transplantation. These morbidities often influence selection of SPK versus living-donor kidney alone (LD KA) transplant. This study quantifies the impact of pancreas graft function on outcomes following SPK. Design, setting, participants, & measurements: Using the SRTR database, SPK wait-listed patients transplanted from 1997 to 2005 were evaluated and segregated as: (1) SPK recipients with functioning pancreas graft 12 mo posttransplant (SPK, P+); (2) SPK recipients with loss of pancreas graft function within 12 mo posttransplant (SPK, P-); (3) recipients of deceased donor (DD) KA; (4) recipients of LD KA. The study compared patient and kidney graft survival to 84 mo posttransplant. Results: Patient survival for SPK, P+ was significantly better than the LD KA; SPK, P-; and DD KA cohorts (88.6% versus 80.0%, 73.9% and 64.8%, respectively [P < 0.001]), a finding confirmed by multivariate analysis and not influenced by pancreas-after-kidney transplantation (PAK) rates and outcomes. Unadjusted graft survival was also highest in the SPK, P+ cohort (72.0% versus 63.6%, 59.8%, 49.7%, P = 0.015 versus LD KA). Conclusions: SPK recipients with functioning pancreas grafts have superior survival compared with LD KA and DD KA, including in the setting of PAK. Early pancreas graft failure results in kidney and patient survival rates similar to KA. These data help further clarify the decision-making of SPK versus KA transplant options for patients and providers. PMID:19406961

  5. Twelve-month pancreas graft function significantly influences survival following simultaneous pancreas-kidney transplantation.

    PubMed

    Weiss, Andrew S; Smits, Gerard; Wiseman, Alexander C

    2009-05-01

    Simultaneous pancreas-kidney transplantation (SPK) is regarded as the treatment of choice for type 1 diabetes (T1DM) and kidney dysfunction, despite the morbidity associated with pancreas transplantation. These morbidities often influence selection of SPK versus living-donor kidney alone (LD KA) transplant. This study quantifies the impact of pancreas graft function on outcomes following SPK. Using the SRTR database, SPK wait-listed patients transplanted from 1997 to 2005 were evaluated and segregated as: (1) SPK recipients with functioning pancreas graft 12 mo posttransplant (SPK, P+); (2) SPK recipients with loss of pancreas graft function within 12 mo posttransplant (SPK, P-); (3) recipients of deceased donor (DD) KA; (4) recipients of LD KA. The study compared patient and kidney graft survival to 84 mo posttransplant. Patient survival for SPK, P+ was significantly better than the LD KA; SPK, P-; and DD KA cohorts (88.6% versus 80.0%, 73.9% and 64.8%, respectively [P < 0.001]), a finding confirmed by multivariate analysis and not influenced by pancreas-after-kidney transplantation (PAK) rates and outcomes. Unadjusted graft survival was also highest in the SPK, P+ cohort (72.0% versus 63.6%, 59.8%, 49.7%, P = 0.015 versus LD KA). SPK recipients with functioning pancreas grafts have superior survival compared with LD KA and DD KA, including in the setting of PAK. Early pancreas graft failure results in kidney and patient survival rates similar to KA. These data help further clarify the decision-making of SPK versus KA transplant options for patients and providers.

  6. Long-term Effects of Delayed Graft Function on Pancreas Graft Survival After Pancreas Transplantation.

    PubMed

    Shin, Sung; Han, Duck Jong; Kim, Young Hoon; Han, Seungbong; Choi, Byung Hyun; Jung, Joo Hee; Cho, Han Kyung

    2014-12-27

    Compared with the impact of delayed graft function (DGF) after renal transplantation, DGF after pancreas transplantation has not been fully evaluated. We retrospectively verified the impact of DGF on long-term pancreas graft survival in surgically successful cases. Pancreas graft failure was defined by the recipient's return to exogenous insulin administration. Between May 2004 and April 2013, we performed 135 technically successful primary pancreas transplantations. Delayed graft function was defined as a total cumulative insulin requirement of 19 UI or greater within postoperative 7 days. Of the 135 recipients in our study cohort, 47 (34.8%) developed DGF after the pancreas transplantation. By multivariate analysis, DGF was found to be associated with a donor age of 30 years or older (odds ratio, 3.4; 95% confidence interval, 1.50-7.69; P=0.003) and the increased ratio of body mass index in a recipient to a donor (odds ratio, 26.1; 95% confidence interval, 2.53-270.0; P=0.006). There was a trend toward higher acute rejection (P=0.622) and mortality (P=0.49) rates in recipients with versus without DGF, although this did not reach statistical significance. Delayed graft function was found to be associated with a greater risk of overall pancreas graft failure (P=0.016) and death-censored graft failure (P=0.037). Delayed graft function after pancreas transplantation was found to be associated with a greater risk of overall pancreas graft failure and death-censored graft failure.

  7. Birth and death of human β-cells in pancreas from cadaver donors, autopsies, surgical specimens, and islets transplanted into mice

    PubMed Central

    Caballero, Francisco; Siniakowicz, Karolina; Jennifer-Hollister-Lock; Duran, Luisa; Katsuta, Hitoshi; Yamada, Takatsugu; Lei, Ji; Deng, Shaoping; Westermark, Gunilla T.; Markmann, James; Bonner-Weir, Susan; Weir, Gordon C.

    2013-01-01

    There is great interest in the potential of the human endocrine pancreas for regeneration by β-cell replication or neogenesis. Our aim was to explore this potential in adult human pancreases and in both islet and exocrine tissue transplanted into mice. The design was to examine pancreases obtained from cadaver donors, autopsies and fresh surgical specimens and compare these findings with those obtained from islet and duct tissue grafted into the kidney. Islets and exocrine tissue were transplanted into normoglycemic ICR/SCID mice and studied 4 and 14 wk later. β-cell replication as assessed by double staining for insulin and Ki67 was 0.22 ± 0.03 % at 4 wk and 0.13 ± 0.03 % at 14 wk. In contrast, no evidence of β-cell replication could be found in 11 cadaver donor and 10 autopsy pancreases. However, Ki67 staining of β-cells in frozen sections obtained at surgery was comparable to that found in transplanted islets. Evidence for neogenesis in transplanted pancreatic exocrine tissue was supported by finding β-cells within the duct epithelium, and the presence of cells double stained for insulin and cytokeratin 19 (CK19). However, β-cells within the ducts never constituted more than 1% of the CK19 positive cells. With confocal microscopy, 7 of 12 examined cells expressed both markers, consistent with a neogeneic process. Mice with grafts containing islet or exocrine tissue were treated with various combinations exendin-4, gastrin and epidermal growth factor; none increased β-cell replication or stimulated neogenesis. In summary, human β-cells replicate at a low level in islets transplanted into mice and in surgical pancreatic frozen sections but rarely in cadaver donor or autopsy pancreases. The absence of β-cell replication in many adult cadaver or autopsy pancreases could, in part, be an artifact of the postmortem state. Thus, it appears that adult human β-cells maintain a low level of turnover through replication and neogenesis. PMID:23321263

  8. Pancreas After Islet Transplantation: A First Report of the International Pancreas Transplant Registry.

    PubMed

    Gruessner, R W G; Gruessner, A C

    2016-02-01

    Pancreas after islet (PAI) transplantation is a treatment option for patients seeking insulin independence through a whole-organ transplant after a failed cellular transplant. This report from the International Pancreas Transplant Registry (IPTR) and the United Network for Organ Sharing (UNOS) studied PAI transplant outcomes over a 10-year time period. Forty recipients of a failed alloislet transplant subsequently underwent pancreas transplant alone (50%), pancreas after previous kidney transplant (22.5%), or simultaneous pancreas and kidney (SPK) transplant (27.5%). Graft and patient survival rates were not statistically significantly different compared with matched primary pancreas transplants. Regardless of the recipient category, overall 1- and 5-year PAI patient survival rates for all 40 cases were 97% and 83%, respectively; graft survival rates were 84% and 65%, respectively. A failed previous islet transplant had no negative impact on kidney graft survival in the SPK category: It was the same as for primary SPK transplants. According to this IPTR/UNOS analysis, a PAI transplant is a safe procedure with low recipient mortality, high graft-function rates in both the short and long term and excellent kidney graft outcomes. Patients with a failed islet transplant should know about this alternative in their quest for insulin independence through transplantation.

  9. Relaparotomy after pancreas transplantation: causes and outcomes.

    PubMed

    Manrique, A; Jiménez, C; López, R M; Cambra, F; Morales, J M; Andrés, A; Gutiérrez, E; Ortuño, T; Calvo, J; Sesma, A G; Moreno, E

    2009-01-01

    Surgical complications after pancreas transplantation, and subsequently relaparotomies, are frequently associated with graft loss, important morbidities, and occasionally patient death. From March 1995 to September 2008, 118 diabetic patients underwent pancreas transplantation: 109 simultaneous pancreas-kidney and nine pancreas after kidney. There were 68 men and 50 women. Mean age at transplantation was 37.8 +/- 7.8 years (range = 25-66). We analyzed donor and recipient characteristics, rate of relaparotomies, risk factors, as well as patient and graft survivals. Forty patients (33.9%) underwent one or more relaparotomies. The causes for relaparotomy were: graft thrombosis in 15 patients (12.7%), bleeding in 14 (11.9%), duodenal stump leak in 7 (5.9%), severe pancreatitis and/or abscess in 5 (4.2%), and small bowel obstruction in 3 (2.5%). Graft pancreatectomy was performed in 52.5% (21 patients). The causes of graft loss were: graft thrombosis in 15 patients (12.7%), bleeding in 14 (11.9%), and duodenal stump leaks in 7 (5.9%). Mortality rate after relaparotomy was 3.38% (four patients). Relaparotomy rate for thrombosis was higher among the portoiliac than the portocaval vein anastomosis group (20.0% vs 10.2%; P = NS), and significantly higher for the bladder drainage than the enteric drainage technique (18.2% vs 5.8%; P < .05). Patients without relaparotomy experienced a significantly higher 5-year graft survival rate than those who underwent relaparotomy (87.2% vs 37.9%; P < .001), but 5-year patient survivals were similar (96.8% without relaparotomy vs 89.6% with relaparotomy). Abdominal complications and the necessity for relaparotomy were associated with important morbidity and significantly reduced pancreas graft survival.

  10. Blame Conformity: Innocent Bystanders Can Be Blamed for a Crime as a Result of Misinformation from a Young, but Not Elderly, Adult Co-Witness

    PubMed Central

    Thorley, Craig

    2015-01-01

    This study examined whether or not exposing an eyewitness to a co-witness statement that incorrectly blames an innocent bystander for a crime can increase the likelihood of the eyewitness subsequently blaming the innocent bystander for the crime. It also examined whether or not the perceived age of the co-witness influences this effect. Participant eyewitnesses first watched a video of a crime featuring a perpetrator and an innocent bystander. They then read one of six bogus co-witness statements about the crime. All were presented as having been written by a female co-witness and they differed in terms of her age (young adult or elderly) and who she blamed for the crime (the perpetrator, the innocent bystander, or nobody). One week later the participants were asked who committed the crime. When the young adult co-witness had blamed the innocent bystander just over 40% of participants subsequently did the same. Few participants (less than 8%) in the other conditions subsequently blamed the innocent bystander. The elderly co-witness was also rated as less credible, less competent, and less accurate than the younger co-witness suggesting eyewitnesses were less likely to be influenced by her incorrect statement as they perceived her to be a less reliable source of information. The applied implications of these findings are discussed. PMID:26230523

  11. Blame Conformity: Innocent Bystanders Can Be Blamed for a Crime as a Result of Misinformation from a Young, but Not Elderly, Adult Co-Witness.

    PubMed

    Thorley, Craig

    2015-01-01

    This study examined whether or not exposing an eyewitness to a co-witness statement that incorrectly blames an innocent bystander for a crime can increase the likelihood of the eyewitness subsequently blaming the innocent bystander for the crime. It also examined whether or not the perceived age of the co-witness influences this effect. Participant eyewitnesses first watched a video of a crime featuring a perpetrator and an innocent bystander. They then read one of six bogus co-witness statements about the crime. All were presented as having been written by a female co-witness and they differed in terms of her age (young adult or elderly) and who she blamed for the crime (the perpetrator, the innocent bystander, or nobody). One week later the participants were asked who committed the crime. When the young adult co-witness had blamed the innocent bystander just over 40% of participants subsequently did the same. Few participants (less than 8%) in the other conditions subsequently blamed the innocent bystander. The elderly co-witness was also rated as less credible, less competent, and less accurate than the younger co-witness suggesting eyewitnesses were less likely to be influenced by her incorrect statement as they perceived her to be a less reliable source of information. The applied implications of these findings are discussed.

  12. Severe impaired deambulation in a patient with vitamin D and mineral deficiency due to exocrine pancreatic insufficiency.

    PubMed

    Christensen, Anton Tedja; Østergård, Torben; Andersen, Vibeke

    2011-09-09

    Skeletal muscle weakness and impaired gait function are common risk factors for disease and even death. Therefore, identification of the modifiable causes of skeletal muscle weakness should have high priority. Knowledge regarding optimal vitamin D treatment in cases of pancreatic insufficiency is scarce. We report a case of a slow decrease in ability to walk distances more than 100 m during the previous 6 months. Low exocrine pancreatic function resulting in phosphorus, magnesium and vitamin D deficiency was found. Medical treatment with peroral pancreatic enzymes, phosphorus, magnesium and i.m. injections of ergocalciferol (vitamin D2) was initiated. Gait function gradually increased to a walking distance of 1,500-3,000 m along with the normalization of the vitamin D and mineral blood levels. Vitamin D deficiency due to exocrine pancreatic insufficiency should be kept in mind as one of the reasons for impaired gait and skeletal muscle weakness.

  13. Volumetric gain of the human pancreas after left partial pancreatic resection: A CT-scan based retrospective study.

    PubMed

    Phillip, Veit; Zahel, Tina; Danninger, Assiye; Erkan, Mert; Dobritz, Martin; Steiner, Jörg M; Kleeff, Jörg; Schmid, Roland M; Algül, Hana

    2015-01-01

    Regeneration of the pancreas has been well characterized in animal models. However, there are conflicting data on the regenerative capacity of the human pancreas. The aim of the present study was to assess the regenerative capacity of the human pancreas. In a retrospective study, data from patients undergoing left partial pancreatic resection at a single center were eligible for inclusion (n = 185). Volumetry was performed based on 5 mm CT-scans acquired through a 256-slice CT-scanner using a semi-automated software. Data from 24 patients (15 males/9 females) were included. Mean ± SD age was 68 ± 11 years (range, 40-85 years). Median time between surgery and the 1st postoperative CT was 9 days (range, 0-27 days; IQR, 7-13), 55 days (range, 21-141 days; IQR, 34-105) until the 2nd CT, and 191 days (range, 62-1902; IQR, 156-347) until the 3rd CT. The pancreatic volumes differed significantly between the first and the second postoperative CT scans (median volume 25.6 mL and 30.6 mL, respectively; p = 0.008) and had significantly increased further by the 3rd CT scan (median volume 37.9 mL; p = 0.001 for comparison with 1st CT scan and p = 0.003 for comparison with 2nd CT scan). The human pancreas shows a measurable and considerable potential of volumetric gain after partial resection. Multidetector-CT based semi-automated volume analysis is a feasible method for follow-up of the volume of the remaining pancreatic parenchyma after partial pancreatectomy. Effects on exocrine and endocrine pancreatic function have to be evaluated in a prospective manner. Copyright © 2015 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  14. [Heterotopic pancreas in the gallbladder. Diagnosis, therapy, and course of a rare developmental anomaly of the pancreas].

    PubMed

    Neupert, G; Appel, P; Braun, S; Tonus, C

    2007-03-01

    Ectopic pancreas is a rare entity but the second most prevalent pancreatic anomaly. Heterotopic pancreas is defined as the presence of pancreatic tissue without any anatomic or vascular continuity with the main body of the pancreas. Its aetiology is not clearly established. In 1916, Poppi published for the first time evidence of heterotopic pancreas in the gallbladder. A review of the literature up to the present showed only 28 more cases worldwide of ectopic pancreas in the gallbladder. Aberrant pancreas is incidentally discovered in 2% of autopsies and has been estimated to occur once in every 500 upper abdominal explorations. Ninety per cent of ectopic pancreas is found in the stomach, duodenum, and jejunum. Mostly it is asymptomatic and benign. For this reason, therapy is indicated only in patients with symptoms such as pyloric obstruction, bleeding, and malignant transformation. Surgical resection or endoscopic mucosal resection as a newer method are recommended.

  15. A new type of exocrine gland and its function in mass recruitment in the ant Cylindromyrmex whymperi (Formicidae, Cerapachyinae)

    NASA Astrophysics Data System (ADS)

    Gobin, Bruno; Rüppell, Olav; Hartmann, Annegret; Jungnickel, Harald; Morgan, David; Billen, Johan

    2001-08-01

    Workers of the ant Cylindromyrmex whymperi display mass trail recruitment. Bioassays show that the trail pheromone originates from a unique gland between abdominal sternites 6 and 7. The gland has a hitherto unknown structural organization. Upon leaving the secretory cell, the duct cell widens to form a sclerotized pear-shaped reservoir chamber, lined with multiple duct cells. Each duct thus forms a miniature reservoir for the secretions of each single secretory cell, a novel structural arrangement in exocrine glands of social Hymenoptera.

  16. The liver is a common non-exocrine target in primary Sjögren's syndrome: A retrospective review

    PubMed Central

    Kaplan, Mariana J; Ike, Robert W

    2002-01-01

    Background The autoimmune destruction of exocrine glands that defines primary Sjögren's syndrome (1°SS) often extends to non-exocrine organs including the liver. We aimed to determine the prevalence of liver disease in patients with 1°SS and to evaluate the association of this complication with other non-exocrine features and serologic markers of autoimmunity and systemic inflammation. Methods We reviewed 115 charts of patients with 1°SS and further analyzed the 73 cases that fulfilled the European Epidemiology Center Criteria, seeking evidence for clinical and subclinical liver disease. Results Liver function tests had been determined in 59 of the 73 patients. Of those, 29 patients (49.1%) had abnormal liver function tests including 20.3% with clinically overt hepatic disease. Liver disease was the most common non-exocrine feature in this cohort. Risk factors for abnormal liver function tests were distributed similarly between the patients with and without liver disease. In 60% of patients with abnormal liver function tests no explanation for this complication was found except for 1°SS. Liver involvement was significantly more common in 1°SS patients who also had evidence of lung, kidney and hematological abnormalities. Patients with abnormal liver function tests were also more likely to have an elevated sedimentation rate and a positive anti-ENA during the course of their disease. Conclusion Liver involvement is a common complication in 1°SS. Its presence correlates with systemic disease. We consider that this complication should be routinely sought in patients with 1°SS, especially when a positive anti-ENA or evidence of systemic inflammation is found. PMID:12230633

  17. Immunocytochemical detection of glucagon and insulin cells in endocrine pancreas and cyclic disparity of plasma glucose in the turtle Melanochelys trijuga.

    PubMed

    Chandavar, Vidya R; Naik, Prakash R

    2008-06-01

    The present investigation was carried out to know the seasonal variation in plasma glucose,insulin and glucagon cells during the reproductive cycle of untreated Melanochelys trijuga. Pancreatic endocrine cells were immunochemically localized.Insulin-immunoreactive (IR) cells occurred in groups of 3-20 and were in close apposition, while glucagon-IR cells were distributed individually between the exocrine pancreas or formed anastomosing cords where cells were not intimately attached. Whenever both IR cell types were present together forming an islet,insulin-IR cells formed clusters in the centre with glucagon-IR cells being scattered at the periphery. Glucagon-IR cells seemed to be secretory throughout the pancreas during the reproductive cycle,while insulin-IR cells were found to be pulsating in their secretion. Mean size of the islet was 1.306, 0.184 and 2.558 mm in the regenerative, reproductive and regressive periods,respectively. In general,insulin-IR cells measured 5.18 (mu)m and glucagon-IR cells 5.22 (mu)m in their longest axis. Invariably, glucagon-IR cells were more in number than insulin-IR cells. The fasting plasma glucose level was 69.97 mg% during the regenerative period, which increased to 97.96 mg% during the reproductive period,and reached a peak value of 113.52 mg% in the regressive period.

  18. Recent advances in transport of water-soluble vitamins in organs of the digestive system: a focus on the colon and the pancreas.

    PubMed

    Said, Hamid M

    2013-11-01

    This review focuses on recent advances in our understanding of the mechanisms and regulation of water-soluble vitamin (WSV) transport in the large intestine and pancreas, two important organs of the digestive system that have only recently received their fair share of attention. WSV, a group of structurally unrelated compounds, are essential for normal cell function and development and, thus, for overall health and survival of the organism. Humans cannot synthesize WSV endogenously; rather, WSV are obtained from exogenous sources via intestinal absorption. The intestine is exposed to two sources of WSV: a dietary source and a bacterial source (i.e., WSV generated by the large intestinal microbiota). Contribution of the latter source to human nutrition/health has been a subject of debate and doubt, mostly based on the absence of specialized systems for efficient uptake of WSV in the large intestine. However, recent studies utilizing a variety of human and animal colon preparations clearly demonstrate that such systems do exist in the large intestine. This has provided strong support for the idea that the microbiota-generated WSV are of nutritional value to the host, and especially to the nutritional needs of the local colonocytes and their health. In the pancreas, WSV are essential for normal metabolic activities of all its cell types and for its exocrine and endocrine functions. Significant progress has also been made in understanding the mechanisms involved in the uptake of WSV and the effect of chronic alcohol exposure on the uptake processes.

  19. Intraductal tubulopapillary neoplasm with expansile invasive carcinoma of the pancreas diagnosed by endoscopic ultrasonography-guided fine needle aspiration: a case report.

    PubMed

    Furuhata, Ayako; Minamiguchi, Sachiko; Mikami, Yoshiki; Kodama, Yuzo; Sumiyoshi, Shinji; Adachi, Souichi; Haga, Hironori

    2014-04-01

    Intraductal tubulopapillary neoplasm (ITPN) of the pancreas, a novel entity included in the World Health Organization 2010 classification, accounts for <1% of all pancreatic exocrine neoplasms and the number of reported cases is limited in the English literature. Herein we describe the cytologic features of ITPN with invasive carcinoma showing expansile growth on endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) cytology. A 74-year-old male patient is presented with a 6.2 cm irregular mass in the head of the pancreas. Microscopic examination of EUS-FNA material showed abundant branching clusters of cells, with some scattered discohesive cells. High power magnification revealed tubular and cribriform patterns with central lumina, containing mucinous or proteinaceous secretions. The constituent cells were relatively uniform and showed mild to intermediate nuclear atypia. Intracytoplasmic mucin was not identified. On cell-block preparation, luminal spaces of clusters contained wispy luminal mucin. Immunohistochemically, constituent cells were positive for MUC1 and MUC6, and were negative for MUC5AC. The large cribriform and tubular clusters with luminal spaces containing wispy mucin were considered to be diagnostic clues for the cytologic diagnosis of ITPN by EUS-FNA. MUC1, MUC6, and MUC5AC immunohistochemistry for cell-block preparation appears to be a useful adjunctive tool to confirm the diagnosis. On EUS-FNA, ITPN should be included in the differential diagnosis of a pancreatic mass lesion showing good circumscription.

  20. Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on Aged Pancreas after Life-Long Coenzyme Q Addition

    PubMed Central

    González-Alonso, Adrián; Ramírez-Tortosa, César L.; Varela-López, Alfonso; Roche, Enrique; Arribas, María I.; Ramírez-Tortosa, M. Carmen; Giampieri, Francesca; Ochoa, Julio J.; Quiles, José L.

    2015-01-01

    An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. In this context, it has been reported that different pancreatic compartments from rats were affected according to the fat composition consumed. Since there is a close relationship between mitochondria, oxidative stress and aging, an experimental approach has been developed to gain more insight into this process in the pancreas. A low dosage of coenzyme Q was administered life-long in rats in order to try to prevent pancreatic aging-related alterations associated to some dietary fat sources. According to that, three groups of rats were fed normocaloric diets containing Coenzyme Q (CoQ) for two years, where virgin olive, sunflower, or fish oil was included as unique fat source. Pancreatic samples for microscopy and blood samples were collected at the moment of euthanasia. The main finding is that CoQ supplementation gives different results according to fat used in diet. When sunflower oil was the main fat in the diet, CoQ supplementation seems to improve endocrine pancreas structure and in particular β-cell mass resembling positive effects of virgin olive oil. Conversely, CoQ intake does not seem to improve the structural alterations of exocrine compartment previously observed in fish oil fed rats. Therefore CoQ may improve pancreatic alterations associated to the chronic intake of some dietary fat sources. PMID:26426013

  1. Sunflower Oil but Not Fish Oil Resembles Positive Effects of Virgin Olive Oil on Aged Pancreas after Life-Long Coenzyme Q Addition.

    PubMed

    González-Alonso, Adrián; Ramírez-Tortosa, César L; Varela-López, Alfonso; Roche, Enrique; Arribas, María I; Ramírez-Tortosa, M Carmen; Giampieri, Francesca; Ochoa, Julio J; Quiles, José L

    2015-09-29

    An adequate pancreatic structure is necessary for optimal organ function. Structural changes are critical in the development of age-related pancreatic disorders. In this context, it has been reported that different pancreatic compartments from rats were affected according to the fat composition consumed. Since there is a close relationship between mitochondria, oxidative stress and aging, an experimental approach has been developed to gain more insight into this process in the pancreas. A low dosage of coenzyme Q was administered life-long in rats in order to try to prevent pancreatic aging-related alterations associated to some dietary fat sources. According to that, three groups of rats were fed normocaloric diets containing Coenzyme Q (CoQ) for two years, where virgin olive, sunflower, or fish oil was included as unique fat source. Pancreatic samples for microscopy and blood samples were collected at the moment of euthanasia. The main finding is that CoQ supplementation gives different results according to fat used in diet. When sunflower oil was the main fat in the diet, CoQ supplementation seems to improve endocrine pancreas structure and in particular β-cell mass resembling positive effects of virgin olive oil. Conversely, CoQ intake does not seem to improve the structural alterations of exocrine compartment previously observed in fish oil fed rats. Therefore CoQ may improve pancreatic alterations associated to the chronic intake of some dietary fat sources.

  2. Recent advances in transport of water-soluble vitamins in organs of the digestive system: a focus on the colon and the pancreas

    PubMed Central

    2013-01-01

    This review focuses on recent advances in our understanding of the mechanisms and regulation of water-soluble vitamin (WSV) transport in the large intestine and pancreas, two important organs of the digestive system that have only recently received their fair share of attention. WSV, a group of structurally unrelated compounds, are essential for normal cell function and development and, thus, for overall health and survival of the organism. Humans cannot synthesize WSV endogenously; rather, WSV are obtained from exogenous sources via intestinal absorption. The intestine is exposed to two sources of WSV: a dietary source and a bacterial source (i.e., WSV generated by the large intestinal microbiota). Contribution of the latter source to human nutrition/health has been a subject of debate and doubt, mostly based on the absence of specialized systems for efficient uptake of WSV in the large intestine. However, recent studies utilizing a variety of human and animal colon preparations clearly demonstrate that such systems do exist in the large intestine. This has provided strong support for the idea that the microbiota-generated WSV are of nutritional value to the host, and especially to the nutritional needs of the local colonocytes and their health. In the pancreas, WSV are essential for normal metabolic activities of all its cell types and for its exocrine and endocrine functions. Significant progress has also been made in understanding the mechanisms involved in the uptake of WSV and the effect of chronic alcohol exposure on the uptake processes. PMID:23989008

  3. [Artificial pancreas for automated glucose control].

    PubMed

    Blauw, Helga; van Bon, Arianne C; de Vries, J H Hans

    2013-01-01

    Strict glucose control is important for patients with diabetes mellitus in order to prevent complications. However, many patients find it difficult to achieve the recommended HbA1c level. The possibility of hypoglycaemia plays an important role in this. The artificial pancreas automates glucose control, improving glucose levels without increasing hypoglycaemic events. The required insulin dose is calculated and administered on the basis of continuous glucose measurements, taking over a large part of the treatment from the patient. Several research groups are working on making this technique suitable for home use. It is expected that the artificial pancreas will become available in the near future. However, effectiveness and safety will have to be investigated in long-term studies. A large number of insulin-dependent patients with diabetes could be eligible for this treatment.

  4. Imaging of the pancreas: Recent advances

    PubMed Central

    Chaudhary, Vikas; Bano, Shahina

    2011-01-01

    A wide spectrum of anomalies of pancreas and the pancreatic duct system are commonly encountered at radiological evaluation. Diagnosing pancreatic lesions generally requires a multimodality approach. This review highlights the new advances in pancreatic imaging and their applications in the diagnosis and management of pancreatic pathologies. The mainstay techniques include computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), radionuclide imaging (RNI) and optical coherence tomography (OCT). PMID:21847450

  5. Pancreas transplants: Evaluation using perfusion scintigraphy

    SciTech Connect

    Kuni, C.C.; du Cret, R.P.; Boudreau, R.J.

    1989-07-01

    To determine the value of scintigraphic perfusion studies in evaluating pancreas transplant patients, we reviewed 56 of these studies in 22 patients who had 27 transplants. Seventeen patients underwent two or more studies. The perfusion studies were performed with 20 mCi (740 MBq) of 99mTc-DTPA injected as a bolus followed by eight to 16 serial 2-sec images and a 500,000-count immediate static image. Images were evaluated for (1) the time and intensity of pancreatic peak radioactivity relative to the time and intensity of the iliac arterial peak; (2) relative pancreatic to iliac arterial intensity on the static image; and (3) size, homogeneity, and definition of the pancreas. Clinical diagnoses at the time of scintigraphy of normal function (n = 36), rejection (n = 13), pancreatitis (n = 6), or arterial thrombosis (n = 1) were based on insulin requirement, urine amylase, serum glucose, serum amylase, response to therapy, cultures, CT, MR, sonography, scintigraphy with 67Ga or 111In-WBCs, percutaneous drainage results, angiography, surgery, and pathologic examination of resected transplants. Three 99mTc-DTPA perfusion studies showed no pancreatic perfusion, four showed decreasing perfusion on serial studies, and five showed progressive loss of definition of the pancreas on serial studies. Of the three patients with no detectable perfusion, one had a normally functioning transplant, one had arterial thrombosis with transplant infarction, and one had severe rejection with minimal function. Decreasing perfusion was associated with rejection in three patients and pancreatitis in one. Decreasing definition was seen in four patients with rejection and one with pancreatitis. We conclude that perfusion scintigraphy is useful, primarily when performed serially, although nonspecific for evaluating pancreas transplants.

  6. "Guilty until proven innocent": the contested use of maternal mortality indicators in global health.

    PubMed

    Storeng, Katerini T; Béhague, Dominique P

    2017-03-15

    The MMR - maternal mortality ratio - has risen from obscurity to become a major global health indicator, even appearing as an indicator of progress towards the global Sustainable Development Goals. This has happened despite intractable challenges relating to the measurement of maternal mortality. Even after three decades of measurement innovation, maternal mortality data are widely presumed to be of poor quality, or, as one leading measurement expert has put it, 'guilty until proven innocent'. This paper explores how and why leading epidemiologists, demographers and statisticians have devoted the better part of the last three decades to producing ever more sophisticated and expensive surveys and mathematical models of globally comparable MMR estimates. The development of better metrics is publicly justified by the need to know which interventions save lives and at what cost. We show, however, that measurement experts' work has also been driven by the need to secure political priority for safe motherhood and by donors' need to justify and monitor the results of investment flows. We explore the many effects and consequences of this measurement work, including the eclipsing of attention to strengthening much-needed national health information systems. We analyse this measurement work in relation to broader political and economic changes affecting the global health field, not least the incursion of neoliberal, business-oriented donors such as the World Bank and the Bill and Melinda Gates Foundation whose institutional structures have introduced new forms of administrative oversight and accountability that depend on indicators.

  7. The genetics of innocence: analysis of 194 U.S. DNA exonerations.

    PubMed

    Hampikian, Greg; West, Emily; Akselrod, Olga

    2011-01-01

    This new analysis of 194 DNA exonerations, representing 171 criminal events, examines the types of evidence and DNA testing that have been used to free the victims of wrongful conviction. The types of DNA testing used to free the innocent parallels the growth of these techniques in forensic science. Short tandem repeat (STR) analysis now prevails (70%), though Y-STR analysis (16%) and mitochondrial testing (10%) are still used when STR analysis is not feasible, and the recently developed mini-STRs have been used for exonerations since 2008 (2.6%). The types of exculpatory evidence included intimate swabs (65%), clothing (53%), hair (13%), fingernail evidence (5%), cigarettes (3%), and other evidence. The most common factor associated with wrongful convictions was misidentification (75%), including misidentification by the victim (65%). False confessions (including admissions and pleas) were obtained in 30% of the cases, and informant testimony (including jailhouse and government informants) was used in 22% of the false convictions. Several types of invalid forensic science testimony were used to wrongfully convict in the 146 trials where transcripts or reliable forensic science data were available for analysis. Invalid testimony included serology (38%), hair comparison (22%), fingerprint comparison (2%), and bite mark comparison (3%). In 43% of the exonerations, the true perpetrator of the crime was identified through postconviction testing.

  8. Effects of Metal Blending in Random Bimetallic Single-Chain Magnets: Synergetic, Antagonistic, or Innocent.

    PubMed

    Wang, Yan-Qin; Yue, Qi; Gao, En-Qing

    2017-01-18

    A family of isomorphous three-dimensional metal-organic frameworks based on bimetallic (FeCo, FeNi, and CoNi) chains with random metal sites have been prepared and magnetically characterized. The solid-solution-type bimetallic materials inherit intrachain ferromagnetic interactions and single-chain-magnet (SCM) behaviors from the homometallic parent materials. Interestingly, different composition dependence of magnetic behaviors has been found. The Fe(II)1-x Ni(II)x series (0≤x≤1) show an innocent composition dependence, where the blocking temperature of slow relaxation decreases monotonically as Fe(II) is replaced by less anisotropic Ni(II) . The Fe(II)1-x Co(II)x series show an unexpected antagonistic blending effect on slow relaxation: blending Fe(II) and Co(II) tends to depress the spin dynamics, and the bimetallic materials with intermediate composition show significantly lower blocking temperature than both Fe(II) and Co(II) materials. This is quite the opposite of what happens in the Co1-x Nix series, where Co(II) and Ni(II) seem to have a synergetic effect so that slow relaxation in bimetallic systems can be promoted to higher temperature than both Co(II) and Ni(II) materials. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Pancreas sparing duodenectomy as an emergency procedure

    PubMed Central

    Paluszkiewicz, Piotr; Dudek, Wojciech; Lowery, Kathryn; Hart, Colin A

    2009-01-01

    Background The operative techniques to close extensive wounds to the duodenum are well described. However, postoperative morbidity is common and includes suture line leak and the formation of fistulae. The aim of this case series is to present pancreas sparing duodenectomy as a safe and viable alternative procedure in the emergency milieu. Methods Five patients underwent emergency pancreas sparing duodenal excisions. Re-implantation of the papilla of Vater or the papilla with a surrounding mucosal patch was performed in two patients. In one, the procedure was further supplemented with a duodenocholangiostomy, stapled pyloric exclusion and enterogastrostomy to defunction the pylorus. In another three patients, distal duodenal excisions were done. Results In four patients, an uneventful recovery was made. One patient died following a myocardial infarction. The surgery lasted meanly 160 minutes with average blood loss of approximately 500 milliliters. The mean hospital stay was 12 days. Enteral nutrition was introduced within the 20 hours after the surgery. Long term follow-up of all surviving patients confirmed a good outcome and normal nutritional status. Conclusion Based on the presented series of patients, we suggest that pancreas-sparing duodenectomy can be considered in selected patients with laceration of the duodenum deemed unsuitable for surgical reconstruction. PMID:19445694

  10. Perforation of jejunal diverticulum with ectopic pancreas.

    PubMed

    Shiratori, Hiroshi; Nishikawa, Takeshi; Shintani, Yukako; Murono, Koji; Sasaki, Kazuhito; Yasuda, Koji; Otani, Kensuke; Tanaka, Toshiaki; Kiyomatsu, Tomomichi; Hata, Keisuke; Kawai, Kazushige; Nozawa, Hiroaki; Ishihara, Soichiro; Fukayama, Masashi; Watanabe, Toshiaki

    2017-04-01

    Perforation of jejunal diverticulum is a rare complication. Here, we report a case of jejunal diverticulum penetration with surrounding ectopic pancreas. An 83-year-old female patient was admitted to our department with acute onset of severe abdominal pain lasting for half a day. Abdominal computed tomography showed outpouching of the small intestine that contained air/fluid, with multiple surrounding air bubbles in the mesentery of the small intestine. She was diagnosed with penetration of the small intestine, and an emergency laparotomy was indicated. The penetrated jejunal diverticulum was identified ~20-cm distal to the ligament of Treitz. Partial resection of the jejunum was performed, and her postoperative course was uneventful. The pathological findings confirmed diverticulum penetration into the mesentery and severe inflammation at the site, with surrounding ectopic pancreas. Furthermore, the pancreatic ducts were opened through the penetrated diverticulum. This rare case shows that the ectopic pancreas might have caused penetration of jejunal diverticulum owing to the pancreatic duct opening through the diverticulum.

  11. Pancreas transplantation: 50 years of experience.

    PubMed

    Casanova, Daniel

    2017-05-01

    In December 1966, the first pancreas transplant ever was performed at the University of Minnesota. R. Lillehei and W. Kelly, transplanted a kidney and a pancreas in a diabetic patient on dialysis, getting function of both organs. Since then, the technical and immunological advances in this transplant have resulted in graft and patient survival results as the rest of the abdominal solid organ transplants. The balance of these 50 years is that more than 50,000 diabetic patients have been transplanted in more than 200 centers around the world. In our country the first transplant was performed 34 years ago in Barcelona and now 12 centers perform about 100 transplants per year. Although advances in diabetes control have been very important, pancreas transplantation continues to be the only method that allows normalization of the carbohydrates metabolism to improve the quality of life and, above all, to increase the survival of these patients. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  12. An integrated multivariable artificial pancreas control system.

    PubMed

    Turksoy, Kamuran; Quinn, Lauretta T; Littlejohn, Elizabeth; Cinar, Ali

    2014-05-01

    The objective was to develop a closed-loop (CL) artificial pancreas (AP) control system that uses continuous measurements of glucose concentration and physiological variables, integrated with a hypoglycemia early alarm module to regulate glucose concentration and prevent hypoglycemia. Eleven open-loop (OL) and 9 CL experiments were performed. A multivariable adaptive artificial pancreas (MAAP) system was used for the first 6 CL experiments. An integrated multivariable adaptive artificial pancreas (IMAAP) system consisting of MAAP augmented with a hypoglycemia early alarm system was used during the last 3 CL experiments. Glucose values and physical activity information were measured and transferred to the controller every 10 minutes and insulin suggestions were entered to the pump manually. All experiments were designed to be close to real-life conditions. Severe hypoglycemic episodes were seen several times during the OL experiments. With the MAAP system, the occurrence of severe hypoglycemia was decreased significantly (P < .01). No hypoglycemia was seen with the IMAAP system. There was also a significant difference (P < .01) between OL and CL experiments with regard to percentage of glucose concentration (54% vs 58%) that remained within target range (70-180 mg/dl). Integration of an adaptive control and hypoglycemia early alarm system was able to keep glucose concentration values in target range in patients with type 1 diabetes. Postprandial hypoglycemia and exercise-induced hypoglycemia did not occur when this system was used. Physical activity information improved estimation of the blood glucose concentration and effectiveness of the control system.

  13. Treatment failure in celiac disease due to coexistent exocrine pancreatic insufficiency.

    PubMed

    Weizman, Z; Hamilton, J R; Kopelman, H R; Cleghorn, G; Durie, P R

    1987-12-01

    A 17-year-old white adolescent had a history of chronic diarrhea, delayed puberty, and growth failure. Investigations excluded cystic fibrosis, Shwachman syndrome, and endocrine causes of growth failure. Severe steatorrhea was diagnosed from fecal fat studies, and a jejunal suction biopsy showed total villus atrophy, consistent with a diagnosis of celiac disease. Following introduction of a gluten-free diet, his appetite and growth improved, but he continued to have abdominal discomfort and loose offensive bowel motions. One year later, severe steatorrhea was present. A repeat jejunal biopsy showed partial recovery of villus architecture. Serum immuno-reactive trypsinogen level was low, which was highly suggestive of exocrine pancreatic failure. Results of quantitative pancreatic stimulation test confirmed the presence of primary pancreatic insufficiency. After introduction of oral pancreatic enzyme supplements with meals, his gastrointestinal symptoms resolved and growth velocity accelerated. Previously, primary pancreatic insufficiency has only been described in elderly patients with long-standing untreated celiac disease. This case, however, emphasizes that pancreatic failure can occur with celiac disease at any age. Determination of a serum immunoreactive trypsinogen level should be considered a useful screening tool for pancreatic insufficiency in patients with celiac disease who have not responded to a gluten-free diet.

  14. Evidence-based Guidelines for the Management of Exocrine Pancreatic Insufficiency After Pancreatic Surgery.

    PubMed

    Sabater, Luis; Ausania, Fabio; Bakker, Olaf J; Boadas, Jaume; Domínguez-Muñoz, J Enrique; Falconi, Massimo; Fernández-Cruz, Laureano; Frulloni, Luca; González-Sánchez, Víctor; Lariño-Noia, José; Lindkvist, Björn; Lluís, Félix; Morera-Ocón, Francisco; Martín-Pérez, Elena; Marra-López, Carlos; Moya-Herraiz, Ángel; Neoptolemos, John P; Pascual, Isabel; Pérez-Aisa, Ángeles; Pezzilli, Raffaele; Ramia, José M; Sánchez, Belinda; Molero, Xavier; Ruiz-Montesinos, Inmaculada; Vaquero, Eva C; de-Madaria, Enrique

    2016-12-01

    To provide evidence-based recommendations for the management of exocrine pancreatic insufficiency (EPI) after pancreatic surgery. EPI is a common complication after pancreatic surgery but there is certain confusion about its frequency, optimal methods of diagnosis, and when and how to treat these patients. Eighteen multidisciplinary reviewers performed a systematic review on 10 predefined questions following the GRADE methodology. Six external expert referees reviewed the retrieved information. Members from Spanish Association of Pancreatology were invited to suggest modifications and voted for the quantification of agreement. These guidelines analyze the definition of EPI after pancreatic surgery, (one question), its frequency after specific techniques and underlying disease (four questions), its clinical consequences (one question), diagnosis (one question), when and how to treat postsurgical EPI (two questions) and its impact on the quality of life (one question). Eleven statements answering those 10 questions were provided: one (9.1%) was rated as a strong recommendation according to GRADE, three (27.3%) as moderate and seven (63.6%) as weak. All statements had strong agreement. EPI is a frequent but under-recognized complication of pancreatic surgery. These guidelines provide evidence-based recommendations for the definition, diagnosis, and management of EPI after pancreatic surgery.

  15. Mediators of exocrine pancreatic secretion induced by intraduodenal application of bile and taurodeoxycholate in man.

    PubMed

    Riepl, R L; Reichardt, B; Rauscher, J; Tzavella, K; Teufel, J; Lehnert, P

    1997-01-01

    The aim of the study was to investigate whether cholecystokinin, neurotensin, and cholinergic mechanisms act as mediators of bile salt-stimulated exocrine pancreatic secretion. Ten fasting healthy subjects provided with a double-lumen tube received 2, 4, and 6 g cattle bile and 200, 400, and 600 mg Na-taurodeoxycholate (TDC) into the duodenum at 65-min intervals, respectively. The application of TDC was repeated in another 10 subjects after intravenous bolus injection of 2.5 micrograms/kg b.w. atropine followed by continuous infusion of 5 micrograms/kg.h. Secretions of volume, bicarbonate, trypsin, and lipase were determined in 10-min fractions of duodenal juice. Plasma samples were analysed for cholecystokinin-like immunoreactivity (CCK-LI) and neurotensin with radioimmunoassays. Volume, bicarbonate, trypsin, and lipase secretion rates were significantly increased by 4 g and 6 g bile and by all doses of TDC. Incremental volume and bicarbonate output was dose-dependently enhanced by bile and TDC, and trypsin and lipase output by bile. Atropine significantly decreased the baseline values and all responses to TDC. Plasma concentrations and integrated CCK-LI and neurotensin significantly increased after 4 and 6 g bile and after 400 and 600 mg TDC. Atropine did not significantly influence peptide release. It is concluded that both hydrokinetic and ecbolic pancreatic secretion stimulated by intraduodenal bile and TDC are dependent on a cholinergic tone. CCK and probably also neurotensin act as further mediators of the ecbolic effect.

  16. Subclinical exocrine pancreatic dysfunction resulting from decreased cholecystokinin secretion in the presence of intestinal villous atrophy.

    PubMed

    Nousia-Arvanitakis, Sanda; Fotoulaki, Maria; Tendzidou, Kyriaki; Vassilaki, Constantina; Agguridaki, Christina; Karamouzis, Michael

    2006-09-01

    The aim of this study was to evaluate the concept that pancreatic dysfunction in patients having gluten sensitivity (celiac disease [CD]) or cow's milk protein enteropathy (CMPE) may result from the lack of pancreatic enzyme stimulation in the absence or decrease of cholecystokinin (CCK) secretion caused by villous atrophy. The following parameters were measured: plasma CCK in response to a fatty meal and human pancreatic fecal elastase in 24 patients with CD while on gluten-free diet and after gluten provocation and in 12 patients with CMPE at diagnosis and after a 6-month period of cow's milk-free diet. Intestinal mucosa morphology was examined by small bowel biopsy. Sixty-three controls having no organic gastrointestinal problems were investigated once at the time of diagnostic evaluation. Fasting CCK, obtained at a time when patients with CD or CMPE had normal intestinal mucosa, was significantly different from postprandial and comparable to that of the control group. Fasting CCK obtained from patients with villous atrophy was also statistically different, but not significantly, from the postprandial. Fasting and postprandial plasma CCK and fecal pancreatic elastase values from patients having normal intestinal mucosa were significantly higher than those obtained from patients with villous atrophy. Significant correlation of intestinal mucosa morphology and CCK with fecal elastase concentration was documented. Exocrine pancreatic dysfunction in individuals having villous atrophy may be the consequence of decreased CCK secretion. Cholecystokinin and pancreatic secretion is restored to normal, with intestinal mucosa regeneration.

  17. VIP and its homologous increase vascular conductance in certain endocrine and exocrine glands

    SciTech Connect

    Huffman, L.J.; Connors, J.M.; Hedge, G.A. )

    1988-04-01

    The effects of vasoactive intestinal peptide (VIP) and related structural homologues on tissue vascular conductances were investigated in anesthetized male rats. VIP, peptide histidine isoleucine (PHI), secretin, growth hormone-releasing factor (GHRF), gastric inhibitory peptide (GIP), or saline was infused intravenously over 4 min. Tissue blood flows were measured during this time by use of {sup 141}Ce-labeled microspheres. Circulating thyrotropin (TSH), triiodothyronine (T{sub 3}), and thyroxine (T{sub 4}) levels were determined before and at 20 min and 2 h after treatment. Marked increases in thyroid, pancreatic, and salivary gland vascular Cs occurred during peptide infusion with the order of potency correlating with the degree of structural homology to VIP. PHI and secretin produced maximal increases in vascular Cs, which were the same as those obtained with VIP. Circulating TSH, T{sub 3}, and T{sub 4} levels were not different from values in saline-infused rats after peptide treatments that caused striking increases in thyroid vascular C. These observations indicate that the vascular beds of certain endocrine and exocrine glands are responsive to the vasodilatory action of VIP and related homologues with the order of potency corresponding to the degree of structural homology to VIP. These results are also consistent with the proposal that structural homologues of VIP act at the same vascular receptor as VIP. Alternative, the involvement of different vascular receptors, acting through the same mechanism at a level beyond the receptor site, cannot be excluded.

  18. [Value of new agonists of the acinar and ductal phases of exocrine secretions].

    PubMed

    Dehaye, J P

    1999-01-01

    Exocrine secretions proceed in two phases which can be studied individually in submandibular glands. We have investigated the response to neuropeptides and purinergic agonists of rat submandibular glands. Pituitary Adenylate Cyclase Activating Peptide (PACAP), an analog of VIP increased the intracellular concentration of cyclic AMP in acinar cells. PACAP also stimulated the activity of the Na(+)-K(+)-2Cl(-)-cotransporter. Extracellular ATP increased the [Ca2+]i in ductal cells. Two distinct receptors were involved in this response. A metabotropic purinergic receptor of the P2Y1 type raised the cellular concentration of IP3 after activating a phospholipase C. The second component of the purinergic response involved an ionotropic P2X7 receptor. After binding an agonist, this receptor formed a non-specific cation channel permeant to calcium and manganese, highly sensitive to inhibition by nickel. Two phospholipases A2 were activated following the occupancy of this receptor. The calcium-independent enzyme triggered kallikrein secretion in response to extracellular ATP. In conclusion, neuropeptides and purinergic agonists activate the acinar and ductal phases of the salivary secretion and are therefore promising candidates for the development of new sialagogues for therapeutic use.

  19. Muscarinic receptors: evidence for a nonuniform distribution in tracheal smooth muscle and exocrine glands

    SciTech Connect

    Basbaum, C.B.; Grillo, M.A.; Widdicombe, J.H.

    1984-02-01

    Muscarinic receptor distribution in smooth muscle, exocrine glands, and epithelium of the ferret trachea was determined using (3H)propylbenzilylcholine mustard ((3H)PrBCM) binding and autoradiography. Specific, atropine-sensitive (3H)PrBCM binding was quantified autoradiographically in the trachealis muscle (approximately 21 binding sites/microns2), surface epithelium (approximately 6 binding sites/microns2), and submucosal glands (approximately 5 binding sites/microns2). Serous and mucous cells in the glands did not differ in receptor density. Binding sites on gland and epithelial cells were associated with basolateral membranes. In the trachealis muscle, a gradient in receptor density was observed, with outer layers of muscle containing 3 to 10 times more receptors per unit area than inner layers. Receptor distribution in both glands and muscle paralleled the distribution of cholinergic axons. However, at the light microscope level, there was no evidence for the presence of receptor ''hot spots'' related to the position of individual axons. The parallelism in the distribution of axons and receptors suggests the possibility of neural control of the genesis and/or maintenance of receptor distribution in these tissues.

  20. Histomorphology of the bottlenose dolphin (Tursiops truncatus) pancreas and association of increasing islet β-cell size with chronic hypercholesterolemia.

    PubMed

    Colegrove, Kathleen M; Venn-Watson, Stephanie

    2015-04-01

    Bottlenose dolphins (Tursiops truncatus) can develop metabolic states mimicking prediabetes, including hyperinsulinemia, hyperlipidemia, elevated glucose, and fatty liver disease. Little is known, however, about dolphin pancreatic histomorphology. Distribution and area of islets, α, β, and δ cells were evaluated in pancreatic tissue from 22 dolphins (mean age 25.7years, range 0-51). Associations of these measurements were evaluated by sex, age, percent high glucose and lipids during the last year of life, and presence or absence of fatty liver disease and islet cell vacuolation. The most common pancreatic lesions identified were exocrine pancreas fibrosis (63.6%) and mild islet cell vacuolation (47.4%); there was no evidence of insulitis or amyloid deposition, changes commonly associated with type 2 diabetes. Dolphin islet architecture appears to be most similar to the pig, where α and β cells are localized to the central or periphery of the islet, respectively, or are well dispersed throughout the islet. Unlike pigs, large islets (greater than 10,000μm(2)) were common in dolphins, similar to that found in humans. A positive linear association was identified between dolphin age and islet area average, supporting a compensatory response similar to other species. The strongest finding in this study was a positive linear association between islet size, specifically β-cells, and percent blood samples with high cholesterol (greater than 280mg/dl, R(2)=0.57). This study is the most comprehensive assessment of the dolphin pancreas to date and may help direct future studies, including associations between chronic hypercholesterolemia and β-cell size.

  1. Diagnosis and treatment of solid pseudopapillary tumor of the pancreas: experience of one single institution from Turkey

    PubMed Central

    2013-01-01

    Background Solid pseudopapillary neoplasia (SPN) of the pancreas is an extremely rare epithelial tumor of low malignant potential. SPN accounts for less than 1% to 2% of exocrine pancreatic tumors. The aim of this study is to report our experience with SPN of the pancreas. It includes a summary of the current literature to provide a reference for the management of this rare clinical entity. Methods A retrospective analysis was performed of all patients diagnosed and treated for SPN in our hospital over the past 15 years (1998 to 2013). A database of the characteristics of these patients was developed, including age, gender, tumor location and size, treatment, and histopathological and immunohistochemical features. Results During this time period, 255 patients with pancreatic malignancy (which does not include ampulla vateri, distal choledocal and duodenal tumor) were admitted to our department, only 10 of whom were diagnosed as having SPN (2.5%). Nine patients were women (90%) and one patient was a man (10%). Their median age was 38.8 years (range 18 to 71). The most common symptoms were abdominal pain and dullness. Seven patients (70%) presented with abdominal pain or abdominal dullness and three patient (30%) were asymptomatic with the diagnosis made by an incidental finding on routine examination. Abdominal computed tomography and/or magnetic resonance imaging showed the typical features of solid pseudopapillary neoplasm in six (60%) of the patients. Four patients underwent distal pancreatectomy with splenectomy, one patient underwent a total mass excision, and one patient underwent total pancreatic resection. Two required extended distal pancreatectomy with splenectomy. Two underwent spleen-preserving distal pancreatectomy. Conclusions SPN is a rare neoplasm that primarily affects young women. The prognosis is favorable even in the presence of distant metastasis. Although surgical resection is generally curative, a close follow-up is advised in order to

  2. Comparative evaluation of structural and functional changes in pancreas after endoscopic and surgical management of pancreatic necrosis.

    PubMed

    Rana, Surinder Singh; Bhasin, Deepak Kumar; Rao, Chalapathi; Sharma, Ravi; Gupta, Rajesh

    2014-01-01

    Patients with acute necrotizing pancreatitis may develop pancreatic insufficiency and this is commonly seen in patients who have undergone surgery for pancreatic necrosis. Owing to the paucity of relative data, we retrospectively evaluated the structural and functional changes in the pancreas after endoscopic and surgical management of pancreatic necrosis. The records of patients who underwent endoscopic transmural drainage of walled off pancreatic necrosis (WOPN) over the last 3 years and who completed at least 6 months of follow up were analyzed. Structural and functional changes in these patients were compared with 25 historical surgical controls (operated in 2005-2006). Twenty six patients (21 M; mean age 35.4±8.1 years) who underwent endoscopic drainage for WOPN were followed up for 22.3±8.6 months. During the follow up, five (19.2%) patients developed diabetes with 3 patients requiring insulin and 1 patient with steatorrhea requiring pancreatic enzyme supplementation. The pancreatic fluid collection (PFC) recurred in 1 patient whose stents spontaneously migrated out. On follow up, in the surgery group, 2 (8%) patients developed steatorrhea and 11 (44%) developed diabetes. Five (20%) of these patients had recurrence of PFC. On comparison of follow up results of endoscopic drainage with surgery, recurrence rates as well as frequency of endocrine and exocrine insufficiency was lower in the endoscopic group but difference was not significant. Structural and functional impairment of pancreas is seen less frequently in patients with pancreatic necrosis treated endoscopically compared to patients undergoing surgery, although the difference was insignificant. Further studies with large sample size are needed to confirm these initial results.

  3. Activation of the epidermal growth factor signalling pathway by tissue plasminogen activator in pancreas cancer cells

    PubMed Central

    Hurtado, Mariano; Lozano, Juan José; Castellanos, Elisabeth; López‐Fernández, Luis A; Harshman, Keith; Martínez‐A, Carlos; Ortiz, Angel R; Thomson, Timothy M; Paciucci, Rosanna

    2007-01-01

    Background Tissue plasminogen activator (tPA) is the major activator of plasminogen in plasma. This serine protease is overexpressed by exocrine pancreas tumour cells, where it promotes tumour cell proliferation, growth, and invasion. Here we have explored the signalling pathways used by tPA to activate the proliferation of pancreatic cancer cells. Methods Transcriptional profiling on cDNA micro arrays was used to analyse the pattern of gene expression in response to tPA compared to the response to epidermal growth factor (EGF) and platelet derived growth factor (PDGF). Results were confirmed using different biochemical assays in which specific kinase inhibitors or RNA interference were used. Results Transcriptional profiling showed that tPA modulates the expression of a set of genes commonly regulated by EGF, but distinct from the major set of genes modulated by PDGF. This suggested that tPA and EGF share common signalling pathways, a conclusion supported by further experimental evidence. Firstly, we found that tPA induced a rapid and transient phosphorylation of the EGFR. Secondly, specific EGFR kinase inhibitors, but not PDGFR kinase inhibitors, abolished the tPA induced phosphorylation of the ERK1/2 kinases and cell proliferation. The mitogenic activity of tPA was also inhibited by siRNA depletion of EGFR, thus confirming the involvement of this receptor in tPA triggered signalling. Thirdly, we show that the signalling and mitogenic effects of tPA require its proteolytic activity, the activity of the metalloprotease‐9 and active hb‐EGF. Conclusion Our results suggest that tPA induces proliferation by triggering a proteolytic cascade that sequentially activates plasmin, metalloprotease‐9 (MMP‐9) and hb‐EGF. These events are required to activate the EGFR signalling pathway and cell proliferation. PMID:17452424

  4. Amazing pancreas: specific regulation of pancreatic secretion of individual digestive enzymes in rats.

    PubMed

    Maouyo, D; Morisset, J

    1995-02-01

    We investigated the effects of somatostatin (SMS)-201-995, atropine, and MK-329 on the role of cholinergic- and cholecystokinin-related systems and on the secretory relationship between five pancreatic digestive enzymes in rats. Animals kept in restraint cages and provided with pancreatic, biliary, duodenal, and jugular vein cannulas were treated as follows: 1) 0.25 micrograms.kg-1.h-1 caerulein alone, 2) both 0.25 micrograms.kg-1.h-1 caerulein and 100 micrograms.kg-1.h-1 atropine, 3) both caerulein and 5 micrograms.kg-1.h-1 SMS, 4) 91.3 micrograms.kg-1.h-1 carbachol alone, 5) both carbachol and 0.5 mg.kg-1.h-1 MK-329, and 6) both carbachol and 5 micrograms.kg-1.h-1 SMS, respectively. Food, but not water, was denied rats starting 10 h before the experiment and throughout the 6-h experimental period. The secretory patterns over the 6-h experimental period showed noticeably independent regulation of pancreatic secretion of individual digestive enzymes. The relationship between paired enzymes significantly varied according to the treatment. The correlation between chymotrypsinogen and the other enzymes was markedly modulated by MK-329. Our results suggest that SMS is a major "gate-keeper" in the regulation of exocrine pancreatic secretion and that the secretion of each digestive enzyme is individually regulated. Furthermore, they suggest that cholecystokinin and acetylcholine and their respective agonists are essentially initiators of secretory processes of the pancreas. Therefore, the paradigms of the regulation of pancreatic secretion heretofore accepted should be reexamined.

  5. Detection, Evaluation and Treatment of Diabetes Mellitus in Chronic Pancreatitis: Recommendations from PancreasFest 2012

    PubMed Central

    Rickels, Michael R.; Bellin, Melena; Toledo, Frederico G.S.; Robertson, R. Paul; Andersen, Dana K.; Chari, Suresh T.; Brand, Randall; Frulloni, Luca; Anderson, Michelle A.; Whitcomb, David C.

    2013-01-01

    Description Diabetes and glucose intolerance are common complications of chronic pancreatitis, yet clinical guidance on their detection, classification, and management is lacking. Methods A working group reviewed the medical problems, diagnostic methods, and treatment options for chronic pancreatitis-associated diabetes for a consensus meeting at PancreasFest 2012. Results Guidance Statement 1.1 Diabetes mellitus is common in chronic pancreatitis. While any patient with chronic pancreatitis should be monitored for development of diabetes, those with long-standing duration of disease, prior partial pancreatectomy, and early onset of calcific disease may be at higher risk. Those patients developing diabetes mellitus are likely to have co-existing pancreatic exocrine insufficiency. Guidance Statement 1.2 Diabetes occurring secondary to chronic pancreatitis should be recognized as pancreatogenic diabetes (type 3c diabetes). Guidance Statement 2.1 The initial evaluation should include fasting glucose and HbA1c. These tests should be repeated annually. Impairment in either fasting glucose or HbA1c requires further evaluation. Guidance Statement 2.2 Impairment in either fasting glucose or HbA1c should be further evaluated by a standard 75 gram oral glucose tolerance test. Guidance Statement 2.3 An absent pancreatic polypeptide response to mixed-nutrient ingestion is a specific indicator of type 3c diabetes. Guidance Statement 2.4 Assessment of pancreatic endocrine reserve, and importantly that of functional beta-cell mass, should be performed as part of the evaluation and follow-up for total pancreatectomy with islet autotransplantation (TPIAT). Guidance Statement 3 Patients with pancreatic diabetes shall be treated with specifically tailored medical nutrition and pharmacologic therapies. Conclusions Physicians should evaluate and treat glucose intolerance in patients with pancreatitis. PMID:23890130

  6. Metastatic Renal Cell Carcinoma to the Pancreas: A Review.

    PubMed

    Cheng, Shaun Kian Hong; Chuah, Khoon Leong

    2016-06-01

    The pancreas is an unusual site for tumor metastasis, accounting for only 2% to 5% of all malignancies affecting the pancreas. The more common metastases affecting the pancreas include renal cell carcinomas, melanomas, colorectal carcinomas, breast carcinomas, and sarcomas. Although pancreatic involvement by nonrenal malignancies indicates widespread systemic disease, metastatic renal cell carcinoma to the pancreas often represents an isolated event and is thus amenable to surgical resection, which is associated with long-term survival. As such, it is important to accurately diagnose pancreatic involvement by metastatic renal cell carcinoma on histology, especially given that renal cell carcinoma metastasis may manifest more than a decade after its initial presentation and diagnosis. In this review, we discuss the clinicopathologic findings of isolated renal cell carcinoma metastases of the pancreas, with special emphasis on separating metastatic renal cell carcinoma and its various differential diagnoses in the pancreas.

  7. Pancreas-after-kidney versus synchronous pancreas-kidney transplantation: comparison of intermediate-term results.

    PubMed

    Bazerbachi, Fateh; Selzner, Markus; Marquez, Max A; Norgate, Andrea; McGilvray, Ian D; Schiff, Jeffrey; Cattral, Mark S

    2013-02-15

    Controversy persists over the safety and efficacy of pancreas transplantation in patients with insulin-dependent diabetes mellitus who have received a prior kidney transplant. We compared the outcomes of recipients who received either Synchronous-Pancreas Kidney-Transplantation (SPK, n=123) or Pancreas-After-Kidney-Transplants(n=49)at our institution between August 2002 to January 2010. Donor and recipient demographics were similar. Time interval between kidney and pancreas transplantation was 5.9 ± 3.8 (4.8 [1.6-12.2]) years. The majority of kidney-recipients in PAK group were transplanted at outside institutions and referred to us for PAK. Most patients received thymoglobulin induction and were maintained on tacrolimus, MMF, and prednisone. For SPK versus PAK recipients, there was no difference in median of length of hospital stay or incidence of overall complications. All PAK recipients are alive with functioning kidney grafts, whereas the 1-, 3-, and 5-year SPK patient survival rates were 98%,96%,and 94%, P=0.09. The 1-,3-, and 5-yr uncensored pancreas survival rates for SPK versus PAK were 93% vs. 90%, 90% vs. 90%, and 82% versus 85%, respectively (P=0.4). Glycemic control and intermediate survival outcomes were similar in both groups. Pancreas-graft outcomes in SPK and PAK were equivalent in our study, but our specific population entailed among other factors a long K to PAK time interval; PAK could be a comparable option to SPK for patients with access to kidney grafts.

  8. ADAPTATION OF GROUP B COXSACKIE VIRUS TO ADULT MOUSE PANCREAS

    PubMed Central

    Dalldorf, Gilbert; Gifford, Rebecca

    1952-01-01

    An alteration of tissue tropism of a Coxsackie virus has been observed following different methods of propagation of the virus in animals. Tropism for the adult mouse pancreas, as described by Pappenheimer, appeared to be irrevocably lost following prolonged brain-to-brain transfer. It was present in the same strain on reisolation from human feces, was intensified following pancreas transfers, and suppressed by brain transfers. Pancreatotropism may be correlated with the titer of virus in the pancreas. PMID:13000059

  9. Pancreas graft salvage using pancreatico-duodenectomy with enteric drainage.

    PubMed

    Reddy, M S; White, S A; Jaques, B C; Torpey, N; Manas, D M

    2007-10-01

    As demand for donor pancreases increases, attempts are being made to utilize even marginal grafts for transplantation. Injury during pancreas recovery can predispose to posttransplant complications and graft loss. Early recognition and correction can salvage these grafts. The authors report an instance of poor segmental perfusion of the pancreas graft that was salvaged by pancreas head resection and enteric drainage through a Roux-en-Y pancreatico-jejunostomy.

  10. A Single-Cell Transcriptomic Map of the Human and Mouse Pancreas Reveals Inter- and Intra-cell Population Structure.

    PubMed

    Baron, Maayan; Veres, Adrian; Wolock, Samuel L; Faust, Aubrey L; Gaujoux, Renaud; Vetere, Amedeo; Ryu, Jennifer Hyoje; Wagner, Bridget K; Shen-Orr, Shai S; Klein, Allon M; Melton, Douglas A; Yanai, Itai

    2016-10-26

    Although the function of the mammalian pancreas hinges on complex interactions of distinct cell types, gene expression profiles have primarily been described with bulk mixtures. Here we implemented a droplet-based, single-cell RNA-seq method to determine the transcriptomes of over 12,000 individual pancreatic cells from four human donors and two mouse strains. Cells could be divided into 15 clusters that matched previously characterized cell types: all endocrine cell types, including rare epsilon-cells; exocrine cell types; vascular cells; Schwann cells; quiescent and activated stellate cells; and four types of immune cells. We detected subpopulations of ductal cells with distinct expression profiles and validated their existence with immuno-histochemistry stains. Moreover, among human beta- cells, we detected heterogeneity in the regulation of genes relating to functional maturation and levels of ER stress. Finally, we deconvolved bulk gene expression samples using the single-cell data to detect disease-associated differential expression. Our dataset provides a resource for the discovery of novel cell type-specific transcription factors, signaling receptors, and medically relevant genes. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. Nonproliferative and Proliferative Lesions of the Gastrointestinal Tract, Pancreas and Salivary Glands of the Rat and Mouse

    PubMed Central

    Nolte, Thomas; Brander-Weber, Patricia; Dangler, Charles; Deschl, Ulrich; Elwell, Michael R.; Greaves, Peter; Hailey, Richard; Leach, Michael W.; Pandiri, Arun R.; Rogers, Arlin; Shackelford, Cynthia C.; Spencer, Andrew; Tanaka, Takuji; Ward, Jerrold M.

    2016-01-01

    The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions in Rats and Mice) project is a joint initiative of the Societies of Toxicologic Pathology from Europe (ESTP), Great Britain (BSTP), Japan (JSTP), and North America (STP) to develop an internationally accepted nomenclature and diagnostic criteria for nonproliferative and proliferative lesions in laboratory animals. The purpose of this publication is to provide a standardized nomenclature and diagnostic criteria for classifying lesions in the digestive system including the salivary glands and the exocrine pancreas of laboratory rats and mice. Most lesions are illustrated by color photomicrographs. The standardized nomenclature, the diagnostic criteria, and the photomicrographs are also available electronically on the Internet (http://www.goreni.org/). Sources of material included histopathology databases from government, academia, and industrial laboratories throughout the world. Content includes spontaneous and age related lesions as well as lesions induced by exposure to test items. Relevant infectious and parasitic lesions are included as well. A widely accepted and utilized international harmonization of nomenclature and diagnostic criteria for the digestive system will decrease misunderstandings among regulatory and scientific research organizations in different countries and provide a common language to increase and enrich international exchanges of information among toxicologists and pathologists. PMID:26973378

  12. The Cyan Fluorescent Protein (CFP) Transgenic Mouse as a Model for Imaging Pancreatic Exocrine Cells

    PubMed Central

    Cao, Hop S Tran; Kimura, Hiroaki; Kaushal, Sharmeela; Snyder, Cynthia S; Reynoso, Jose; Hoffman, Robert M; Bouvet, Michael

    2015-01-01

    Context The use of fluorescent proteins for in vivo imaging has opened many new areas of research. Among the important advances in the field have been the development of transgenic mice expressing various fluorescent proteins. Objective To report whole-body and organ-specific fluorescence imaging to characterize the transgenic cyan fluorescent protein mouse. Design Mice were imaged using two devices. Brightfield images were obtained with the OV100 Small Animal Imaging System (Olympus Corp., Tokyo, Japan). Fluorescence imaging was performed under the cyan fluorescent protein filter using the iBox Small Animal Imaging System (UVP, Upland, CA, USA). Intervention All animals were sacrificed immediately before imaging. They were imaged before and throughout multiple steps of a complete necropsy. Harvested organs were also imaged with both devices. Selected organs were then frozen and processed for histology, fluorescence microscopy, and H&E staining. Fluorescence microscopy was performed with an Olympus IMT-2 inverted fluorescence microscope. Main outcome measure Determination of fluorescence intensity of different organs. Results Surprisingly, we found that there is differential enhancement of fluorescence among organs; most notably, the pancreas stands out from the rest of the gastrointestinal tract, displaying the strongest fluorescence of all organs in the mouse. Fluorescence microscopy demonstrated that the cyan fluorescent protein fluorescence resided in the acinar cells of the pancreas and not the islet cells. Conclusions The cyan fluorescent protein mouse should lead to a deeper understanding of pancreatic function and pathology, including cancer. PMID:19287108

  13. The cyan fluorescent protein (CFP) transgenic mouse as a model for imaging pancreatic exocrine cells.

    PubMed

    Tran Cao, Hop S; Kimura, Hiroaki; Kaushal, Sharmeela; Snyder, Cynthia S; Reynoso, Jose; Hoffman, Robert M; Bouvet, Michael

    2009-03-09

    The use of fluorescent proteins for in vivo imaging has opened many new areas of research. Among the important advances in the field have been the development of transgenic mice expressing various fluorescent proteins. To report whole-body and organ-specific fluorescence imaging to characterize the transgenic cyan fluorescent protein mouse. Mice were imaged using two devices. Brightfield images were obtained with the OV100 Small Animal Imaging System (Olympus Corp., Tokyo, Japan). Fluorescence imaging was performed under the cyan fluorescent protein filter using the iBox Small Animal Imaging System (UVP, Upland, CA, USA). All animals were sacrificed immediately before imaging. They were imaged before and throughout multiple steps of a complete necropsy. Harvested organs were also imaged with both devices. Selected organs were then frozen and processed for histology, fluorescence microscopy, and H&E staining. Fluorescence microscopy was performed with an Olympus IMT-2 inverted fluorescence microscope. Determination of fluorescence intensity of different organs. Surprisingly, we found that there is differential enhancement of fluorescence among organs; most notably, the pancreas stands out from the rest of the gastrointestinal tract, displaying the strongest fluorescence of all organs in the mouse. Fluorescence microscopy demonstrated that the cyan fluorescent protein fluorescence resided in the acinar cells of the pancreas and not the islet cells. The cyan fluorescent protein mouse should lead to a deeper understanding of pancreatic function and pathology, including cancer.

  14. Effects of pancreas transplantation on late complications of diabetes and metabolic effects of pancreas and islet transplantation.

    PubMed

    Caldara, R; La Rocca, E; Maffi, P; Secchi, A

    1999-01-01

    Pancreas transplantation has become an accepted therapeutic approach to treat insulin-dependent diabetes mellitus, successfully restoring normoglycemia. In contrast, islet transplantation is still in the experimental phase, only a few operations having being performed world-wide. The aim of this review is to analyze the effects of pancreas transplantation on the late complications of diabetes and to report the endocrino-metabolic effects of pancreas and islet transplantation.

  15. Neovascularisation is not an Innocent Bystander in Recurrence after Great Saphenous Vein Surgery

    PubMed Central

    Prakash, V

    2015-01-01

    Introduction This study sought to establish the causes of failure of great saphenous vein surgery among patients in whom there was confidence that accurate saphenofemoral ligation had been carried and the great saphenous vein had been stripped at least to knee level. Methods This was an observational study of 100 limbs (66 patients) operated on by a single surgeon 5–22 years previously (mean: 12 years). The index operation was primary in 54 limbs and for recurrence in 46 limbs. Thirty-two patients were studied having been re-referred for recurrence while 34 were recalled for review. All were examined clinically and with duplex ultrasonography, and all completed questionnaires (Aberdeen varicose vein questionnaire [AVVQ] and EQ-5D-3L). In order to measure the extent of visible recurrence, a scoring system similar to that in the venous clinical severity score was used but with a range of 0–8. Results There were visible varicosities in 77 of the 100 limbs. Duplex ultrasonography showed that recurrent saphenofemoral incompetence (SFI) was present in 27% of the limbs. This was judged to result from neovascularisation and was the most common source of reflux. AVVQ scores for the 27 limbs with recurrent SFI (median: 34, interquartile range [IQR]: 20–42) were higher than for the 73 with no recurrent SFI (median: 17, IQR: 11–29), which was a significant difference (Mann–Whitney U test, p<0.01). Analysing clinical scores with chi-squared tests indicated fewer visible varicosities in limbs without recurrent SFI than in those with recurrent SFI (p<0.01). Conclusions Neovascularisation remains poorly understood but it cannot be considered an innocent bystander. PMID:25723685

  16. Exocrine pancreatic function in children with coeliac disease before and after a gluten free diet.

    PubMed Central

    Carroccio, A; Iacono, G; Montalto, G; Cavataio, F; Di Marco, C; Balsamo, V; Notarbartolo, A

    1991-01-01

    This study was designed to determine the extent of pancreatic insufficiency in untreated coeliac disease and whether pancreatic secretion is impaired after a prolonged gluten free period. Three groups of patients were studied: group A comprised 44 patients, mean (SD) age 4.0 (3.1) years, with coeliac disease and total or subtotal atrophy of the intestinal mucosa; group B comprised 67 patients, mean age 4.4 (3.0) years, with coeliac disease but with normal morphology of the intestinal villi (after 12.9 months of a gluten free diet); group C comprised 49 control subjects, mean age 3.2 (3.0) years, with normal jejunal histology. In all subjects exocrine pancreatic function was determined by the secretin-caerulein test; bicarbonate concentration and lipase, phospholipase, and chymotrypsin activity were measured after an intravenous injection of secretin 1 clinical unit (CU) + caerulein 75 ng/kg body weight. Faecal chymotrypsin concentration was also assayed. No significant difference was found between values of the duodenal output of pancreatic enzymes and bicarbonate obtained in the three groups; however, 10 of 44 untreated coeliac patients showed tryptic or lipolytic activity, or both, below the normal limit for our laboratory. The mean value of the faecal chymotrypsin concentration was significantly lower in untreated than in treated coeliac patients (p less than 0.0001) or in control subjects (p less than 0.0001). It is concluded that untreated coeliac patients may have pancreatic deficiency independent of a decrease in enterohormone release. No primary or secondary pancreatic insufficiency was found in coeliac patients where the intestinal mucosa had returned to normal. PMID:1855688

  17. Relationships between occupational history and serum concentrations of organochlorine compounds in exocrine pancreatic cancer.

    PubMed

    Bosch de Basea, Magda; Porta, Miquel; Alguacil, Joan; Puigdomènech, Elisa; Gasull, Magda; Garrido, José A; López, Tomàs

    2011-05-01

    Previous studies investigating associations between occupational history and risk of exocrine pancreatic cancer (EPC) did not use biomarkers of exposure. The only two studies that measured internal concentrations of organochlorine compounds (OCs) in EPC did not analyse their relationship with occupation. To analyse the relationship between occupational history and blood concentrations of seven OCs in patients with EPC. Incident cases of EPC were prospectively identified, and during hospital admission were interviewed face-to-face on occupational history and life-style factors (n = 135). Occupations were coded according to the International Standard of Occupations 1988. Some occupational exposures were also assessed with the Finnish job-exposure matrix (Finjem). Serum concentrations of OCs were analysed by high-resolution gas chromatography with electron-capture detection. Craftsmen and related trades workers had significantly higher concentrations of polychlorinated biphenyl (PCB) congeners 138, 153 and 180. Years worked in agriculture did not influence concentrations of p,p'-DDT, p,p'-DDE, hexachlorobenzene or β-hexachlorocyclohexane. Subjects who ever worked in agriculture had lower concentrations of PCBs (all p < 0.05). Occupational exposure to lead, nickel and low frequency magnetic fields was significantly associated with higher concentrations of PCBs. Certain occupations were associated with higher concentrations of PCBs, suggesting that these compounds may account for some increased risks found in previous studies. The lack of association between work in agriculture and concentrations of OC pesticides is consistent with occupation playing a lesser role than diet in influencing OC concentrations. Occupational studies on the relationships among exposure to industrial agents and EPC risk may need to consider adjusting for exposure to PCBs.

  18. Monoclonal Antibodies as Probes for Unique Antigens in Secretory Cells of Mixed Exocrine Organs

    NASA Astrophysics Data System (ADS)

    Basbaum, C. B.; Mann, J. K.; Chow, A. W.; Finkbeiner, W. E.

    1984-07-01

    In the past, it has been difficult to identify the secretory product and control mechanisms associated with individual cell types making up mixed exocrine organs. This report establishes the feasibility of using immunological methods to characterize both the biochemical constituents and regulatory mechanisms associated with secretory cells in the trachea. Monoclonal antibodies directed against components of tracheal mucus were produced by immunizing mice with dialyzed, desiccated secretions harvested from tracheal organ culture. An immunofluorescence assay revealed that of the total 337 hybridomas screened, 100 produced antibodies recognizing goblet cell granules; 64, gland cell granules; and 3, antigen confined to the ciliated apical surface of the epithelium. The tracheal goblet cell antibody described in this report was strongly cross-reactive with intestinal goblet cells, as well as with a subpopulation of submandibular gland cells, but not with cells of Brunner's glands or the ciliated cell apical membrane. The serous cell antibody was not cross-reactive with goblet, Brunner's gland, or submandibular cells, or the ciliated cell apical membrane. The antibody directed against the apical membrane of ciliated cells did not cross-react with gland or goblet cells or the apical membrane of epithelial cells in the duodenum. Monoclonal antibodies, therefore, represent probes by which products unique to specific cells or parts of cells in the trachea can be distinguished. The antibodies, when used in enzyme immunoassays, can be used to quantitatively monitor secretion by individual cell types under a variety of physiological and pathological conditions. They also provide the means for purification and characterization of cell-specific products by immunoaffinity chromatography.

  19. Food and nutrient intakes and K‐ras mutations in exocrine pancreatic cancer

    PubMed Central

    Morales, Eva; Porta, Miquel; Vioque, Jesús; López, Tomàs; Mendez, Michelle A; Pumarega, José; Malats, Núria; Crous‐Bou, Marta; Ngo, Joy; Rifà, Juli; Carrato, Alfredo; Guarner, Luisa; Corominas, Josep M; Real, Francisco X

    2007-01-01

    Background No studies have investigated the relation between K‐ras mutations and dietary factors in exocrine pancreatic cancer (EPC), and fewer than 10 studies have done so in other neoplasms. Patients and Methods Incident cases of EPC were prospectively identified, and interviewed face‐to‐face during hospital admission. Food and nutrient intakes were measured with a food frequency questionnaire. Logistic regression was used to compare EPC cases (n = 107) with and without K‐ras mutations (case‐case study). Results K‐ras mutations were more common among daily consumers of milk and other dairy products than among non‐daily consumers: the odds ratio adjusted by total energy, age, sex, smoking, alcohol and coffee consumption (ORa) was 5.1 (95% CI 1.1 to 24.5, p = 0.040). For all dairy products, including butter, the ORa for the medium and upper tertiles of intake were 5.4 and 11.6, respectively (p for trend = 0.023). The ORa for regular coffee drinkers further adjusted by dairy consumption was 4.7 (95% CI 1.1 to 20.7, p = 0.043). K‐ras mutated cases reported a lower intake of vitamin E (ORa = 0.2, p for trend = 0.036), polyunsaturated fats and omega 3 fatty acids (ORa = 0.2; p for trend <0.03). Conclusions Results support the hypothesis that in EPC exposure to specific dietary components or contaminants may influence the occurrence or persistence of K‐ras mutations. PMID:17568059

  20. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21st century

    PubMed Central

    Trang, Tony; Chan, Johanna; Graham, David Y

    2014-01-01

    Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy. PMID:25206255

  1. Ultrastructural changes in exocrine tissues of a DeltaF-508 CFTR mouse model.

    PubMed

    Thomopoulos, G N; Shori, D K; Asking, B; Kosta, A; Dimopoulou, A; Paterson, K; Hartley, R; Colledge, W H

    2001-01-01

    Cystic fibrosis (CF) is characterized by abnormal secretion from epithelial cells. We wanted to detect changes in the ultrastructural characteristics of cells within a number of exocrine tissues, including the colon, submandibular and parotid salivary glands of DeltaF-508 CFTR animals. Therefore, in the present study a DeltaF-508 CFTR mouse model was compared to control, by applying conventional and complex carbohydrates staining techniques to tissue sections at the electron microscope level. The colon of DeltaF-508 CFTR mice contained thick mucous secretions that harbored many bacteria, along with cytoplasmic fragments and leukocytes. Leukocytes were also seen to infiltrate the cytoplasm of goblet cells. Tissues were taken before, 10 min after isoprenaline, and 30 min after a further injection of methacholine. In the submandibular gland, there is limited secretory activity after isoprenaline treatment, and this increases further with methacholine treatment. Depletion of the secretory granules of acinar cells is observed, following the combined isoprenaline and methacholine treatment, but no significant changes in granule numbers occurred in granular tubule cells. Glycogen, abundant before treatment, is reduced within 10 min of isoprenaline treatment and is completely exhausted by 30 min, especially in the convoluted granular tubule cells. A few secretory granules in acinar and in granular tubule cells of the DeltaF-508 CFTR submandibular glands displayed two electron densities. The secretory responses of the parotid gland cells were similar to those in submandibular gland cells, except that in these DeltaF-508 CFTR cells, secretory granules appeared more polymorphic in structure than those found in control animals.

  2. Relationships between leucine and the pancreatic exocrine function for improving starch digestibility in ruminants.

    PubMed

    Liu, K; Liu, Y; Liu, S M; Xu, M; Yu, Z P; Wang, X; Cao, Y C; Yao, J H

    2015-04-01

    Four Holstein heifers (215 ± 7 kg; means ± SD), fitted with one pancreatic pouch, duodenal re-entrant cannulas, and duodenal infusion catheters, were used in this experiment. In phase 1, the 24-h profile of pancreatic fluid was determined. Pancreatic fluid flow peaked 1h after feeding, but peaks of similar magnitude also occurred before the morning feed, necessitating 24-h collection of pancreatic fluid to estimate daily excretion. In phase 2, the effects of duodenal infusions of 0, 10, 20, or 30 g of leucine on pancreatic fluid flow were determined in a 4 × 4 Latin square design. The leucine was infused for 12h in 2,500 mL of the infusate, and samples of pancreatic fluid and jugular blood were collected in 1-h intervals from the beginning of the infusion for 36 h. The results showed that the secretion rate of pancreatic fluid (mL/h) was significantly higher in 10-g leucine group than the other groups (mL/h). Protein concentration (mg/mL) in pancreatic fluid was elevated proportional to the amount of leucine infused. Leucine infusions increased both the concentration (U/mL) and secretion rate (U/h) of α-amylase. Infusion of 10 g of leucine also increased the secretion rates (U/h) of trypsin, chymotrypsin, and lipase, but did not change their concentrations. No significant effects of leucine infusions on plasma glucose and insulin concentrations were found. The results indicate that leucine could act as a nutrient signal to stimulate α-amylase production and pancreatic exocrine function in dairy heifers.

  3. A morphometrical study of the exocrine pancreatic cell in fasted and fed frogs

    PubMed Central

    1979-01-01

    The influence of feeding on the ultrastruct of the frog exocrine pancreatic cell was studied by morphometrical procedures. Volume and surface of various cell structures were measured and expressed per unit cell volume. The average cellular size was not influenced by feeding. Though protein synthesis changes 5-to 10-fold (van Venrooij, W. J., and C. Poort. 1971. Biochim. Biophys. Acta. 247:468-470), no significant differences were observed in the amount of membrane that constitutes the rough endoplasmic reticulum (RER) and that represented the major part of total cellular membranes. The appearance of the RER changed. When fasted, most of its membrane was arranged in stacks of tightly packed, narrow cisternae. Within 4 h after feeding, these cisternae were separated and irregularly dilated, and ribosomes became ordered in typical rosettes on their surface. The total volume of the Golgi system increased twofold after feeding. The vesicular and tubular elements at the Golgi periphery did not change, but the volumes of the Golgi cisternae and the condensing vacuoles increased 2.5- and 6-fold, respectively. The increased in the amount of membrane present in these structures was only 1.6- and 3.5-fold, which reflects the more distended appearance of the cisternae and the rounded shape of the condensing vacuoles after feeding. Feeding halved the number of secretory granules per cell, and signs of exocytosis were more common than in fasted animals. These findings suggest that, in the frog pancreatic cell, fluctuations in the production of secretory proteins are not accompanied by an important breakdown and renewal of cellular membranes. This may favor a rapid and strong response of the cell to feeding. PMID:313397

  4. Current Perspectives on Laparoscopic Robot-Assisted Pancreas and Pancreas-Kidney Transplantation

    PubMed Central

    Boggi, Ugo; Signori, Stefano; Vistoli, Fabio; Amorese, Gabriella; Consani, Giovanni; De Lio, Nelide; Perrone, Vittorio; Croce, Chiara; Marchetti, Piero; Cantarovich, Diego; Mosca, Franco

    2011-01-01

    Pancreas transplant recipients continue to suffer high surgical morbidity. Current robotic technology provides a unique opportunity to test whether laparoscopy can improve the post-operative course of pancreas transplantation (PT). Current knowledge on robotic pancreas and renal transplantation was reviewed to determine feasibility and safety of robotic PT. Information available from literature was included in this review, together with personal experience including three PT, and two renal allotransplants. As of April 2011, the relevant literature provides two case reports on robotic renal transplantation. The author’s experience consists of one further renal allotransplantation, two solitary PT, and one simultaneous pancreas-kidney transplantation. Information obtained at international conferences include several other renal allotransplants, but no additional PT. Preliminary data show that PT is feasible laparoscopically under robotic assistance, but raises concerns regarding the effects of increased warm ischemia time on graft viability. Indeed, during construction of vascular anastomoses, graft temperature progressively increases, since maintenance of a stable graft temperature is difficult to achieve laparoscopically. There is no proof that progressive graft warming produces actual damage to transplanted organs, unless exceedingly long. However, this important question is likely to elicit a vibrant discussion in the transplant community. PMID:21720670

  5. Adenocarcinoma of the pancreas: CT imaging.

    PubMed

    Horton, Karen M; Fishman, Elliot K

    2002-12-01

    CT currently plays a vital role in pancreatic cancer staging. Continued advancements in computers, scanner technology, and 3D software have improved CT detection of smaller masses and staging. In particular, the introduction of MDCT and real-time 3D volume-rendering software have greatly improved the visualization of the pancreas and adjacent vasculature. This progress will continue as manufacturers introduce the next generation of scanners, which can acquire up to 32 slices per second with ever faster scan times. The impact of these new scanners on diagnostic accuracy will need to be carefully evaluated.

  6. Annular pancreas associated with duodenal carcinoma

    PubMed Central

    Brönnimann, Enrico; Potthast, Silke; Vlajnic, Tatjana; Oertli, Daniel; Heizmann, Oleg

    2010-01-01

    Annular pancreas (AP) is a rare congenital anomaly. Coexisting malignancy has been reported only in a few cases. We report what is, to the best of our knowledge, the first case in the English literature of duodenal adenocarcinoma in a patient with AP. In a 55-year old woman with duodenal outlet stenosis magnetic resonance cholangiopancreatography showed an aberrant pancreatic duct encircling the duodenum. Duodenojejunostomy was performed. Eight weeks later she presented with painless jaundice. Duodenopancreatectomy revealed a duodenal adenocarcinoma, surrounded by an incomplete AP. Thus, co-existent malignancy with AP can be present without obstructive jaundice and without being visible through preoperative diagnostics. PMID:20593508

  7. Noninvasive investigation of exocrine pancreatic function: Feasibility of cine dynamic MRCP with a spatially selective inversion-recovery pulse.

    PubMed

    Yasokawa, Kazuya; Ito, Katsuyoshi; Tamada, Tsutomu; Yamamoto, Akira; Hayashida, Minoru; Tanimoto, Daigo; Higaki, Atsushi; Noda, Yasufumi; Kido, Ayumu

    2015-11-01

    To investigate the feasibility of noncontrast-enhanced cine dynamic magnetic resonance cholangiopancreatography (MRCP) with a spatially selective inversion-recovery (IR) pulse for evaluating exocrine pancreatic function in comparison with the N-benzoyl-L-tyrosyl-p-aminobenzoic acid (BT-PABA) test as a pancreatic exocrine function test. Twenty subjects with or without chronic pancreatitis were included. MRCP with a spatially selective IR pulse was repeated every 15 seconds for 5 minutes to acquire a total of 20 images (cine-dynamic MRCP). The median and mean frequency of the observation (the number of times) and the moving distance (mean secretion grading scores) of pancreatic juice inflow on cine-dynamic MRCP were compared with a BT-PABA test. The urinary PABA excretion rate (%) had significant positive correlations with both the mean secretion grade (r = 0.66, P = 0.002) and frequency of secretory inflow (r = 0.62, P = 0.004) in cine dynamic MRCP. Both the mean frequency of observations of pancreatic secretory inflow (1.4 ± 1.6 times vs. 14.3 ± 4.2 times, P < 0.001) and the mean secretion grade (grade = 0.16 ± 0.24 vs. grade = 1.81 ± 0.81, P < 0.001) was significantly lower in the chronic pancreatitis group than in the normal subject group. Cine dynamic MRCP with a spatially selective IR pulse may have potential for estimating the pancreatic exocrine function noninvasively as a substitute for the BT-PABA test. © 2015 Wiley Periodicals, Inc.

  8. [Prevention of traumatic pancreatitis in injuries of the pancreas].

    PubMed

    Tolstoĭ, A D

    1985-05-01

    Based on the investigation of results of the treatment of more than 200 patients with various injuries of the pancreas recommendations are given for the prophylactics of traumatic pancreatitis. A combination of different surgical measures on the pancreas and other organs are recommended as well as a purposeful medicamental treatment.

  9. Squamous Cell Carcinoma of Pancreas: Mystery and Facts.

    PubMed

    Raghavapuram, Saikiran; Vaid, Arjun; Rego, Rayburn F

    2015-08-01

    Squamous cell carcinoma of the pancreas is very rare as pancreas does not have any squamous cells. Only a few cases have been reported in the literature so far. We describe such a case where in the patient presented with painless jaundice. CT and EUS confirmed the pancreatic mass biopsy of which showed squamous cell cancer.

  10. [Ectopic pancreas mimicking advanced gastric malignancy--case report].

    PubMed

    Zawada, Iwona; Lewosiuk, Agnieszka; Hnatyszyn, Krzysztof; Patalan, Michał; Woyke, Stanisław; Kostyrka, Roman; Marlicz, Krzysztof; Starzyńska, Teresa

    2012-04-01

    Ectopic pancreas is the most common type of ectopic tissue in gastrointestinal tract. It is typically asymptomatic, presenting as a small submucosal lesion in prepyloric region of stomach. The diagnosis is usually incidental, during gastroscopy. The patient with symptomatic heterotropic pancreas, mimicking gastric malignancy was described.

  11. Three types of simultaneous pancreas and kidney transplantation.

    PubMed

    Kobayashi, T; Gruessner, A C; Wakai, T; Sutherland, D E R

    2014-04-01

    The purposes of this study were to study and compare clinical and functional outcomes after simultaneous deceased donor pancreas and kidney transplantation (SPK DD), simultaneous deceased donor pancreas and living donor kidney transplantation (SPK DL), and simultaneous living donor pancreas and kidney transplantation (SPK LL). From January 1, 1996 to September 1, 2005, 8918 primary, simultaneous pancreas and kidney transplantation (SPK) procedures were reported to the International Pancreas Transplant Registry. Of these, 8764 (98.3%) were SPK DD, 115 (1.3%) were SPK DL, and 39 (0.4%) were SPK LL. We compared these 3 groups with regard to several endpoints including patient and pancreas and kidney graft survival rates. The 1-year and 3-year patient survival rates for SPK DD were 95% and 90%, 97% and 95% for SPK DL, and 100% and 100% for SPK LL recipients, respectively (P ≥ .07). The 1-year and 3-year pancreas graft survival rates for SPK DD were 84% and 77%, 83% and 71% for SPK DL, and 90% and 84% for SPK LL recipients, respectively (P ≥ .16). The 1-year and 3-year kidney graft survival rates for SPK DD were 92% and 84%, 94% and 86% for SPK DL, and 100% and 89% for SPK LL recipients, respectively (P ≥ .37). Patient survival rates and graft survival rates for pancreas and kidney were similar among the 3 groups evaluated in this study. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Artificial Pancreas Project at Cambridge 2013.

    PubMed

    Hovorka, R

    2015-08-01

    The development and clinical testing of closed-loop systems (the artificial pancreas) is underpinned by advances in continuous glucose monitoring and benefits from concerted academic and industry collaborative efforts. This review describes the progress of the Artificial Pancreas Project at the University of Cambridge from 2006 to 2014. Initial studies under controlled laboratory conditions, designed to collect representative safety and performance data, were followed by short to medium free-living unsupervised outpatient studies demonstrating the safety and efficacy of closed-loop insulin delivery using a model predictive control algorithm. Accompanying investigations included assessment of the psychosocial impact and key factors affecting glucose control such as insulin kinetics and glucose absorption. Translation to other disease conditions such as critical illness and Type 2 diabetes took place. It is concluded that innovation of iteratively enhanced closed-loop systems will provide tangible means to improve outcomes and quality of life in people with Type 1 diabetes and their families in the next decade. © 2015 The Author. Diabetic Medicine © 2015 Diabetes UK.

  13. Design Considerations for Artificial Pancreas Pivotal Studies.

    PubMed

    Russell, Steven J; Beck, Roy W

    2016-07-01

    The development of artificial pancreas systems has evolved to the point that pivotal studies designed to assess efficacy and safety are in progress or soon to be initiated. These pivotal studies are intended to provide the necessary data to gain clearance from the U.S. Food and Drug Administration, coverage by payers, and adoption by patients and clinicians. Although there will not be one design that is appropriate for every system, there are certain aspects of protocol design that will be considerations in all pivotal studies designed to assess efficacy and safety. One key aspect of study design is the intervention to be used by the control group. A case can be made that the control group should use the currently available best technology, which is sensor-augmented pump therapy. However, an equally, if not more, compelling case can be made that the control intervention should be usual care. In this Perspective, we elaborate on this issue and provide a pragmatic approach to the design of clinical trials of artificial pancreas systems.

  14. Two synchronous malignant tumors of the pancreas: a case report.

    PubMed

    De Silva, W S L; Pathirana, A A; Prematilleke, I; Rajapakse, S A P D; Hettiarachchi, P S H; Manawasinghe, D S; Dassanayake, B K

    2017-03-28

    Only a limited number of multiple synchronous primary malignancies of the pancreas have been reported in the medical literature. We report a case of two solid malignant tumors of the pancreas diagnosed preoperatively. We describe a 65-year-old Sri Lankan woman who presented with progressive obstructive jaundice. Initial contrast-enhanced computed tomography imaging detected a malignant tumor at the tail of her pancreas. A second tumor of the pancreatic head was detected with integrated imaging using multidetector computed tomography and multimodal magnetic resonance imaging. She underwent total pancreaticoduodenectomy and splenectomy. Gross examination of the specimen confirmed the presence of two separate tumors. Histology of the ampullary tumor showed pancreatic-type adenocarcinoma and the tumor in the tail of her pancreas showed a colloid-type adenocarcinoma. The possibility of multiple primary malignant solid tumors of different types with malignant potential has to be considered even without background pathology when managing multiple tumors in the pancreas.

  15. [Tuberculosis of the pancreas--a clinical rarity].

    PubMed

    Heitmann, P; Kratsch, B; Löschke, S; Klempa, I

    2001-06-01

    Pancreas tuberculosis is a rare diagnosis and is usually associated with miliary spread. Only a few cases are reported in the literature. A female patient was admitted with a history of uncharacteristic abdominal pain, weight loss, weakness, and intermittent fever. CA 19-9 was increased and the CT scan showed an irregular mass in the pancreatic tail. Suspecting the diagnosis of pancreatic cancer, a pancreas tail resection with splenectomy was performed. The histological examination showed pancreas tuberculosis. Mimicking pancreatic cancer or presenting with acute/chronic pancreatitis or obstructive jaundice, the diagnosis of pancreas tuberculosis is very difficult to make and is usually established after surgical treatment. Although pancreas tuberculosis is rare, it should be considered when evaluating a pancreatic mass.

  16. Technical failure of the pancreas after SPK transplant: are these patients good candidates for later pancreas retransplant?

    PubMed

    Wang, Shen-Nien; Sturdevant, Mark; Kandaswamy, Raja; Gruessner, Rainer G W; Sutherland, David E R; Humar, Abhinav

    2008-01-01

    Technical failure of the pancreas graft after a simultaneous pancreas-kidney (SPK) transplant is not uncommon, affecting roughly 10% of SPK recipients. These patients often recover with good kidney function, but have persistent issues related to their diabetes. The aim of this study was to determine if these patients were good candidates for a later pancreas retransplant. Outcomes were compared between 21 PASPK (pancreas after SPK) recipients and 361 recipients of a primary pancreas after kidney (PAK) transplant. Except for kidney graft source, there was no significant difference in the demographic characteristics between these two groups. In general, early surgical complications were more common in PASPK than PAK recipients (47.6% vs. 35.5%, p = 0.15), although the difference was not statistically significant. The incidence of acute rejection was no different between these two groups (28% vs. 33%, p = NS). At three yr post-transplant, patient and pancreas graft survival rates were also no different between the two groups (p = NS). The most common cause for graft loss in both groups was acute or chronic rejection. In conclusion, pancreas retransplant is a viable option for SPK recipients experiencing early technical failure of the pancreas graft. These recipients are not at higher immunologic risk vs. primary PAK recipients.

  17. Actinobaculum schaalii - invasive pathogen or innocent bystander? A retrospective observational study

    PubMed Central

    2011-01-01

    (42.5%) it is often overlooked or considered a contaminant. Detection of Actinobaculum schaalii in clinical isolates mainly reflects infection indicating that this Gram-positive rod is not an innocent bystander. PMID:22029906

  18. Intraductal papillary mucinous carcinoma of the pancreas associated with pancreas divisum: a case report and review of the literature.

    PubMed

    Nishi, Takeshi; Kawabata, Yasunari; Ishikawa, Noriyoshi; Araki, Asuka; Yano, Seiji; Maruyama, Riruke; Tajima, Yoshitsugu

    2015-07-08

    Pancreas divisum, the most common congenital anomaly of the pancreas, is caused by failure of the fusion of the ventral and dorsal pancreatic duct systems during embryological development. Although various pancreatic tumors can occur in patients with pancreas divisum, intraductal papillary mucinous neoplasm is rare. A 77-year-old woman was referred to our hospital because she was incidentally found to have a cystic tumor in her pancreas at a regular health checkup. Contrast-enhanced abdominal computed tomography images demonstrated a cystic tumor in the head of the pancreas measuring 40 mm in diameter with slightly enhancing mural nodules within the cyst. Endoscopic retrograde pancreatography via the major duodenal papilla revealed a cystic tumor and a slightly dilated main pancreatic duct with an abrupt interruption at the head of the pancreas. The orifice of the major duodenal papilla was remarkably dilated and filled with an abundant extrusion of mucin, and the diagnosis based on pancreatic juice cytology was "highly suspicious for adenocarcinoma". Magnetic resonance cholangiopancreatography depicted a normal, non-dilated dorsal pancreatic duct throughout the pancreas. The patient underwent a pylorus-preserving pancreaticoduodenectomy under the diagnosis of intraductal papillary mucinous neoplasm with suspicion of malignancy arising in the ventral part of the pancreas divisum. A pancreatography via the major and minor duodenal papillae on the surgical specimen revealed that the ventral and dorsal pancreatic ducts were not connected, and the tumor originated in the ventral duct, i.e., the Wirsung's duct. Microscopically, the tumor was diagnosed as intraductal papillary mucinous carcinoma with microinvasion. In addition, marked fibrosis with acinar cell depletion was evident in the ventral pancreas, whereas no fibrotic change was noted in the dorsal pancr