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Sample records for regulate exocrine granule

  1. PPARγ regulates exocrine pancreas lipase.

    Science.gov (United States)

    Danino, Hila; Naor, Ronny Peri-; Fogel, Chen; Ben-Harosh, Yael; Kadir, Rotem; Salem, Hagit; Birk, Ruth

    2016-12-01

    Pancreatic lipase (triacylglycerol lipase EC 3.1.1.3) is an essential enzyme in hydrolysis of dietary fat. Dietary fat, especially polyunsaturated fatty acids (PUFA), regulate pancreatic lipase (PNLIP); however, the molecular mechanism underlying this regulation is mostly unknown. As PUFA are known to regulate expression of proliferator-activated receptor gamma (PPARγ), and as we identified in-silico putative PPARγ binding sites within the putative PNLIP promoter sequence, we hypothesized that PUFA regulation of PNLIP might be mediated by PPARγ. We used in silico bioinformatics tools, reporter luciferase assay, PPARγ agonists and antagonists, PPARγ overexpression in exocrine pancreas AR42J and primary cells to study PPARγ regulation of PNLIP. Using in silico bioinformatics tools we mapped PPARγ binding sites (PPRE) to the putative promoter region of PNLIP. Reporter luciferase assay in AR42J rat exocrine pancreas acinar cells transfected with various constructs of the putative PNLIP promoter showed that PNLIP transcription is significantly enhanced by PPARγ dose-dependently, reaching maximal levels with multi PPRE sites. This effect was significantly augmented in the presence of PPARγ agonists and reduced by PPARγ antagonists or mutagenesis abrogating PPRE sites. Over-expression of PPARγ significantly elevated PNLIP transcript and protein levels in AR42J cells and in primary pancreas cells. Moreover, PNLIP expression was up-regulated by PPARγ agonists (pioglitazone and 15dPGJ2) and significantly down-regulated by PPARγ antagonists in non-transfected rat exocrine pancreas AR42J cell line cells. PPARγ transcriptionally regulates PNLIP gene expression. This transcript regulation resolves part of the missing link between dietary PUFA direct regulation of PNLIP. Copyright © 2016 Elsevier B.V. All rights reserved.

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

    International Nuclear Information System (INIS)

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

    1986-01-01

    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

  3. Serglycin proteoglycan is not implicated in localizing exocrine pancreas enzymes to zymogen granules

    DEFF Research Database (Denmark)

    Niemann, Carsten U; Cowland, Jack B; Ralfkiaer, Elisabeth

    2009-01-01

    Storage and release of proteins from granules forms the basis of cellular functions as diverse as cell mediated cytotoxicity, neuronal communication, activation of muscle fibres, and release of hormones or digestive enzymes from endocrine and exocrine glands, such as the pancreas. Serglycin...... is the major intracellular proteoglycan of haematopoietic cells. Serglycin is important for localization of proteins in granules of different haematopoietic cell types. Previous reports have indicated a role for serglycin in granule formation and localization of zymogens in granules of the exocrine pancreas...... in rat. We here present data showing that serglycin is not present at the protein level in human or murine pancreas. Furthermore, the amount and localization of three exocrine pancreas zymogens (amylase, trypsinogen, and carboxypeptidase A) is not affected by the absence of serglycin in a serglycin knock...

  4. Sorting of a HaloTag protein that has only a signal peptide sequence into exocrine secretory granules without protein aggregation.

    Science.gov (United States)

    Fujita-Yoshigaki, Junko; Matsuki-Fukushima, Miwako; Yokoyama, Megumi; Katsumata-Kato, Osamu

    2013-11-15

    The mechanism involved in the sorting and accumulation of secretory cargo proteins, such as amylase, into secretory granules of exocrine cells remains to be solved. To clarify that sorting mechanism, we expressed a reporter protein HaloTag fused with partial sequences of salivary amylase protein in primary cultured parotid acinar cells. We found that a HaloTag protein fused with only the signal peptide sequence (Met(1)-Ala(25)) of amylase, termed SS25H, colocalized well with endogenous amylase, which was confirmed by immunofluorescence microscopy. Percoll-density gradient centrifugation of secretory granule fractions shows that the distributions of amylase and SS25H were similar. These results suggest that SS25H is transported to secretory granules and is not discriminated from endogenous amylase by the machinery that functions to remove proteins other than granule cargo from immature granules. Another reporter protein, DsRed2, that has the same signal peptide sequence also colocalized with amylase, suggesting that the sorting to secretory granules is not dependent on a characteristic of the HaloTag protein. Whereas Blue Native PAGE demonstrates that endogenous amylase forms a high-molecular-weight complex, SS25H does not participate in the complex and does not form self-aggregates. Nevertheless, SS25H was released from cells by the addition of a β-adrenergic agonist, isoproterenol, which also induces amylase secretion. These results indicate that addition of the signal peptide sequence, which is necessary for the translocation in the endoplasmic reticulum, is sufficient for the transportation and storage of cargo proteins in secretory granules of exocrine cells.

  5. Exocrine gland dysfunction in MC5-R-deficient mice: evidence for coordinated regulation of exocrine gland function by melanocortin peptides.

    Science.gov (United States)

    Chen, W; Kelly, M A; Opitz-Araya, X; Thomas, R E; Low, M J; Cone, R D

    1997-12-12

    The effects of pituitary-derived melanocortin peptides are primarily attributed to ACTH-mediated adrenocortical glucocorticoid production. Identification of a widely distributed receptor for ACTH/MSH peptides, the melanocortin-5 receptor (MC5-R), suggested non-steroidally mediated systemic effects of these peptides. Targeted disruption of the MC5-R produced mice with a severe defect in water repulsion and thermoregulation due to decreased production of sebaceous lipids. High levels of MC5-R was found in multiple exocrine tissues, including Harderian, preputial, lacrimal, and sebaceous glands, and was also shown to be required for production and stress-regulated synthesis of porphyrins by the Harderian gland and ACTH/MSH-regulated protein secretion by the lacrimal gland. These data show a requirement for the MC5-R in multiple exocrine glands for the production of numerous products, indicative of a coordinated system for regulation of exocrine gland function by melanocortin peptides.

  6. Targeting developmental regulators of zebrafish exocrine pancreas as a therapeutic approach in human pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Nelson S. Yee

    2012-02-01

    Histone deacetylases (HDACs and RNA polymerase III (POLR3 play vital roles in fundamental cellular processes, and deregulation of these enzymes has been implicated in malignant transformation. Hdacs and Polr3 are required for exocrine pancreatic epithelial proliferation during morphogenesis in zebrafish. We aim to test the hypothesis that Hdacs and Polr3 cooperatively control exocrine pancreatic growth, and combined inhibition of HDACs and POLR3 produces enhanced growth suppression in pancreatic cancer. In zebrafish larvae, combination of a Hdac inhibitor (Trichostatin A and an inhibitor of Polr3 (ML-60218 synergistically prohibited the expansion of exocrine pancreas. In human pancreatic adenocarcinoma cells, combination of the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA and ML-60218 produced augmented suppression of colony formation and proliferation, and induction of cell cycle arrest and apoptotic cell death. The enhanced cytotoxicity was associated with supra-additive upregulation of the pro-apoptotic regulator BAX and the cyclin-dependent kinase inhibitor p21CDKN1A. tRNAs have been shown to have pro-proliferative and anti-apoptotic roles, and SAHA-stimulated expression of tRNAs was reversed by ML-60218. These findings demonstrate that chemically targeting developmental regulators of exocrine pancreas can be translated into an approach with potential impact on therapeutic response in pancreatic cancer, and suggest that counteracting the pro-malignant side effect of HDAC inhibitors can enhance their anti-tumor activity.

  7. Role of pancreatic polypeptide in the regulation of pancreatic exocrine secretion in dogs

    International Nuclear Information System (INIS)

    Shiratori, Keiko; Lee, K.Y.; Chang, Tamin; Jo, Y.H.; Coy, D.H.; Chey, W.Y.

    1988-01-01

    The effect of intravenous infusion of synthetic human pancreatic polypeptide (HPP) or a rabbit anti-PP serum on pancreatic exocrine secretion was studied in 10 dogs with gastric and Thomas duodenal cannulas. The infusion of HPP, achieved a plasma PP concentration that mimicked the peak plasma concentration of PP in both interdigestive and postprandial states. This dose of HPP significantly inhibited pancreatic secretion in the interdigestive state. By contrast, immunoneutralization of circulating PP by a rabbit anti-PP serum resulted in significant increases in both interdigestive and postprandial pancreatic secretion, including water, bicarbonate, and protein. The increase in the pancreatic secretion paralleled a decrease in circulating PP level, which lasted for as long as 5 days. Furthermore, the anti-PP serum blocked the inhibitory action of exogenous HPP on pancreatic exocrine secretion. The present study indicates that endogenous PP plays a significant role in the regulation of the pancreatic exocrine secretion in both interdigestive and digestive states. Thus the authors conclude that PP is another hormone regulating pancreatic exocrine secretion in dogs

  8. Gastrin is not a physiological regulator of pancreatic exocrine secretion in the dog

    International Nuclear Information System (INIS)

    Koehler, E.; Beglinger, C.; Eysselein, V.; Groetzinger, U.; Gyr, K.

    1987-01-01

    The role of gastrin as a regulator of exocrine pancreatic secretion has not been proven adequately. In the present study the authors therefore compared the relative molar potencies of sulfated and unsulfated gastrin 17 with structurally related CCK peptides (synthetic CCK-8 and natural porcine CCK-33) in stimulating exocrine pancreatic secretion in conscious dogs. Dose response curves were constructed for pancreatic and gastric acid secretion. Plasma gastrin levels after exogenous gastrin 17-I and -II were compared with postprandial gastrin concentrations. The molar potency estimates calculated with synthetic CCK8 as standard for pancreatic protein secretion were natural porcine 50% pure CCK-33 1.60, gastrin 17-I 0.12, and gastrin 17-II 0.16. All four peptides induced a dose-dependent increase in pancreatic bicarbonate output. However, the blood concentrations needed to stimulate pancreatic secretion were above the postprandial gastrin levels. The data indicate that both gastrin 17 peptides are not physiological regulators of pancreatic enzyme secretion in dogs

  9. PKCalpha regulates platelet granule secretion and thrombus formation in mice.

    Science.gov (United States)

    Konopatskaya, Olga; Gilio, Karen; Harper, Matthew T; Zhao, Yan; Cosemans, Judith M E M; Karim, Zubair A; Whiteheart, Sidney W; Molkentin, Jeffery D; Verkade, Paul; Watson, Steve P; Heemskerk, Johan W M; Poole, Alastair W

    2009-02-01

    Platelets are central players in atherothrombosis development in coronary artery disease. The PKC family provides important intracellular mechanisms for regulating platelet activity, and platelets express several members of this family, including the classical isoforms PKCalpha and PKCbeta and novel isoforms PKCdelta and PKCtheta. Here, we used a genetic approach to definitively demonstrate the role played by PKCalpha in regulating thrombus formation and platelet function. Thrombus formation in vivo was attenuated in Prkca-/- mice, and PKCalpha was required for thrombus formation in vitro, although this PKC isoform did not regulate platelet adhesion to collagen. The ablation of in vitro thrombus formation in Prkca-/- platelets was rescued by the addition of ADP, consistent with the key mechanistic finding that dense-granule biogenesis and secretion depend upon PKCalpha expression. Furthermore, defective platelet aggregation in response to either collagen-related peptide or thrombin could be overcome by an increase in agonist concentration. Evidence of overt bleeding, including gastrointestinal and tail bleeding, was not seen in Prkca-/- mice. In summary, the effects of PKCalpha ablation on thrombus formation and granule secretion may implicate PKCalpha as a drug target for antithrombotic therapy.

  10. Transient receptor potential ion channel Trpm7 regulates exocrine pancreatic epithelial proliferation by Mg2+-sensitive Socs3a signaling in development and cancer

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    Nelson S. Yee

    2011-03-01

    Genetic analysis of pancreatic development has provided new insights into the mechanisms underlying the formation of exocrine pancreatic neoplasia. Zebrafish sweetbread (swd mutants develop hypoplastic acini and dysmorphic ducts in the exocrine pancreas, with impeded progression of cell division cycle and of epithelial growth. Positional cloning and allelic complementation have revealed that the swd mutations affect the transient receptor potential melastatin-subfamily member 7 (trpm7 gene, which encodes a divalent cation-permeable channel with kinase activity. Supplementary Mg2+ partially rescued the exocrine pancreatic defects of the trpm7 mutants by improving cell-cycle progression and growth and repressing the suppressor of cytokine signaling 3a (socs3a gene. The role of Socs3a in Trpm7-mediated signaling is supported by the findings that socs3a mRNA level is elevated in the trpm7 mutants, and antisense inhibition of socs3a expression improved their exocrine pancreatic growth. TRPM7 is generally overexpressed in human pancreatic adenocarcinoma. TRPM7-deficient cells are impaired in proliferation and arrested in the G0-G1 phases of the cell division cycle. Supplementary Mg2+ rescued the proliferative defect of the TRPM7-deficient cells. Results of this study indicate that Trpm7 regulates exocrine pancreatic development via the Mg2+-sensitive Socs3a pathway, and suggest that aberrant TRPM7-mediated signaling contributes to pancreatic carcinogenesis.

  11. The Prohormone VGF Regulates β Cell Function via Insulin Secretory Granule Biogenesis

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    Samuel B. Stephens

    2017-09-01

    Full Text Available The prohormone VGF is expressed in neuroendocrine and endocrine tissues and regulates nutrient and energy status both centrally and peripherally. We and others have shown that VGF-derived peptides have direct action on the islet β cell as secretagogues and cytoprotective agents; however, the endogenous function of VGF in the β cell has not been described. Here, we demonstrate that VGF regulates secretory granule formation. VGF loss-of-function studies in both isolated islets and conditional knockout mice reveal a profound decrease in stimulus-coupled insulin secretion. Moreover, VGF is necessary to facilitate efficient exit of granule cargo from the trans-Golgi network and proinsulin processing. It also functions to replenish insulin granule stores following nutrient stimulation. Our data support a model in which VGF operates at a critical node of granule biogenesis in the islet β cell to coordinate insulin biosynthesis with β cell secretory capacity.

  12. Purinergic receptors in the endocrine and exocrine pancreas.

    Science.gov (United States)

    Novak, I

    2008-09-01

    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 beta cells, stimulation of P2Y(1) 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 P2Y(1) receptors, there is also evidence for other P2 and adenosine receptors in beta cells (P2Y(2), P2Y(4), P2Y(6), P2X subtypes and A(1) receptors) and in glucagon-secreting alpha cells (P2X(7), A(2) 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 P2Y(2), P2Y(4), P2Y(11), P2X(4) and P2X(7) receptors could regulate secretion, primarily by affecting Cl(-) and K(+) channels and intracellular Ca(2+) 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.

  13. Ca2+-dependent K+ Channels in Exocrine Salivary Glands

    Science.gov (United States)

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

    2014-01-01

    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, Ca2+-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 Ca2+-activated K+ channel of intermediate single channel conductance encoded by the KCNN4 gene; and, 2) a voltage- and Ca2+-dependent K+ channel of large single channel conductance encoded by the KCNMA1 gene. This review focuses on the physiological roles of Ca2+-dependent K+ channels in exocrine salivary glands. We also discuss interesting recent findings on the regulation of Ca2+-dependent K+ channels by protein-protein interactions that may significantly impact exocrine gland physiology. PMID:24559652

  14. Granule protein processing and regulated secretion in neutrophils

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    Avinash eSheshechalam

    2014-09-01

    Full Text Available Neutrophils are part of a family of granulocytes that, together with eosinophils and basophils, play an essential role in innate immunity. Neutrophils are the most abundant circulating leukocytes and are vital for rapid immune responses, being recruited to sites of injury or infection within minutes, where they can act as specialized phagocytic cells. However, another prominent function of neutrophils is the release of pro-inflammatory compounds, including cytokines, chemokines and digestive enzymes, which are stored in intracellular compartments and released through regulated exocytosis. Hence, an important feature that contributes to rapid immune responses is capacity of neutrophils to synthesize and store pre-formed pro-inflammatory mediators in specialized intracellular vesicles and thus no new synthesis is required. This review will focus on advancement in three topics relevant to neutrophil secretion. First we will examine what is known about basal level pro-inflammatory mediator synthesis, trafficking and storage in secretory compartments. Second, we will review recent advancements in the mechanisms that control vesicle mobilization and the release of pre-formed mediators. Third, we will examine the upregulation and de novo synthesis of pro-inflammatory mediators by neutrophils engaged at sites of infection.

  15. TIA-1 Self-Multimerization, Phase Separation, and Recruitment into Stress Granules Are Dynamically Regulated by Zn2+

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    Joseph B. Rayman

    2018-01-01

    Full Text Available Summary: Stress granules are non-membranous structures that transiently form in the cytoplasm during cellular stress, where they promote translational repression of non-essential RNAs and modulate cell signaling by sequestering key signal transduction proteins. These and other functions of stress granules facilitate an adaptive cellular response to environmental adversity. A key component of stress granules is the prion-related RNA-binding protein, T cell intracellular antigen-1 (TIA-1. Here, we report that recombinant TIA-1 undergoes rapid multimerization and phase separation in the presence of divalent zinc, which can be reversed by the zinc chelator, TPEN. Similarly, the formation and maintenance of TIA-1-positive stress granules in arsenite-treated cells are inhibited by TPEN. In addition, Zn2+ is released in cells treated with arsenite, before stress granule formation. These findings suggest that Zn2+ is a physiological ligand of TIA-1, acting as a stress-inducible second messenger to promote multimerization of TIA-1 and subsequent localization into stress granules. : Rayman et al. show that Zn2+ is a stress-inducible second messenger that triggers self-multimerization and phase separation of TIA-1 and regulates dynamic recruitment of TIA-1 into stress granules. This mechanism is part of an adaptive cellular response to environmental adversity. Keywords: TIA-1, TIA1, stress granules, cellular stress, functional prion, phase separation, zinc regulation

  16. Pancreatic exocrine function testing

    International Nuclear Information System (INIS)

    Goff, J.S.

    1981-01-01

    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

  17. Pancreatic Exocrine Function Testing

    OpenAIRE

    Berk, J. Edward

    1982-01-01

    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 par...

  18. MMP-13 regulates growth of wound granulation tissue and modulates gene expression signatures involved in inflammation, proteolysis, and cell viability.

    Directory of Open Access Journals (Sweden)

    Mervi Toriseva

    Full Text Available Proteinases play a pivotal role in wound healing by regulating cell-matrix interactions and availability of bioactive molecules. The role of matrix metalloproteinase-13 (MMP-13 in granulation tissue growth was studied in subcutaneously implanted viscose cellulose sponge in MMP-13 knockout (Mmp13(-/- and wild type (WT mice. The tissue samples were harvested at time points day 7, 14 and 21 and subjected to histological analysis and gene expression profiling. Granulation tissue growth was significantly reduced (42% at day 21 in Mmp13(-/- mice. Granulation tissue in Mmp13(-/- mice showed delayed organization of myofibroblasts, increased microvascular density at day 14, and virtual absence of large vessels at day 21. Gene expression profiling identified differentially expressed genes in Mmp13(-/- mouse granulation tissue involved in biological functions including inflammatory response, angiogenesis, cellular movement, cellular growth and proliferation and proteolysis. Among genes linked to angiogenesis, Adamts4 and Npy were significantly upregulated in early granulation tissue in Mmp13(-/- mice, and a set of genes involved in leukocyte motility including Il6 were systematically downregulated at day 14. The expression of Pdgfd was downregulated in Mmp13(-/- granulation tissue in all time points. The expression of matrix metalloproteinases Mmp2, Mmp3, Mmp9 was also significantly downregulated in granulation tissue of Mmp13(-/- mice compared to WT mice. Mmp13(-/- mouse skin fibroblasts displayed altered cell morphology and impaired ability to contract collagen gel and decreased production of MMP-2. These results provide evidence for an important role for MMP-13 in wound healing by coordinating cellular activities important in the growth and maturation of granulation tissue, including myofibroblast function, inflammation, angiogenesis, and proteolysis.

  19. Who Regulates Whom? An Overview of RNA Granules and Viral Infections

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    Natalia Poblete-Durán

    2016-06-01

    Full Text Available After viral infection, host cells respond by mounting an anti-viral stress response in order to create a hostile atmosphere for viral replication, leading to the shut-off of mRNA translation (protein synthesis and the assembly of RNA granules. Two of these RNA granules have been well characterized in yeast and mammalian cells, stress granules (SGs, which are translationally silent sites of RNA triage and processing bodies (PBs, which are involved in mRNA degradation. This review discusses the role of these RNA granules in the evasion of anti-viral stress responses through virus-induced remodeling of cellular ribonucleoproteins (RNPs.

  20. COUP-TFI mitotically regulates production and migration of dentate granule cells and modulates hippocampal Cxcr4 expression.

    Science.gov (United States)

    Parisot, Joséphine; Flore, Gemma; Bertacchi, Michele; Studer, Michèle

    2017-06-01

    Development of the dentate gyrus (DG), the primary gateway for hippocampal inputs, spans embryonic and postnatal stages, and involves complex morphogenetic events. We have previously identified the nuclear receptor COUP-TFI as a novel transcriptional regulator in the postnatal organization and function of the hippocampus. Here, we dissect its role in DG morphogenesis by inactivating it in either granule cell progenitors or granule neurons. Loss of COUP-TFI function in progenitors leads to decreased granule cell proliferative activity, precocious differentiation and increased apoptosis, resulting in a severe DG growth defect in adult mice. COUP-TFI-deficient cells express high levels of the chemokine receptor Cxcr4 and migrate abnormally, forming heterotopic clusters of differentiated granule cells along their paths. Conversely, high COUP-TFI expression levels downregulate Cxcr4 expression, whereas increased Cxcr4 expression in wild-type hippocampal cells affects cell migration. Finally, loss of COUP-TFI in postmitotic cells leads to only minor and transient abnormalities, and to normal Cxcr4 expression. Together, our results indicate that COUP-TFI is required predominantly in DG progenitors for modulating expression of the Cxcr4 receptor during granule cell neurogenesis and migration. © 2017. Published by The Company of Biologists Ltd.

  1. Dynamic development of starch granules and the regulation of starch biosynthesis in Brachypodium distachyon: comparison with common wheat and Aegilops peregrina.

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    Chen, Guanxing; Zhu, Jiantang; Zhou, Jianwen; Subburaj, Saminathan; Zhang, Ming; Han, Caixia; Hao, Pengchao; Li, Xiaohui; Yan, Yueming

    2014-08-06

    Thorough understanding of seed starch biosynthesis and accumulation mechanisms is of great importance for agriculture and crop improvement strategies. We conducted the first comprehensive study of the dynamic development of starch granules and the regulation of starch biosynthesis in Brachypodium distachyon and compared the findings with those reported for common wheat (Chinese Spring, CS) and Aegilops peregrina. Only B-granules were identified in Brachypodium Bd21, and the shape variation and development of starch granules were similar in the B-granules of CS and Bd21. Phylogenetic analysis showed that most of the Bd21 starch synthesis-related genes were more similar to those in wheat than in rice. Early expression of key genes in Bd21 starch biosynthesis mediate starch synthesis in the pericarp; intermediate-stage expression increases the number and size of starch granules. In contrast, these enzymes in CS and Ae. peregrina were mostly expressed at intermediate stages, driving production of new B-granules and increasing the granule size, respectively. Immunogold labeling showed that granule-bound starch synthase (GBSSI; related to amylose synthesis) was mainly present in starch granules: at lower levels in the B-granules of Bd21 than in CS. Furthermore, GBSSI was phosphorylated at threonine 183 and tyrosine 185 in the starch synthase catalytic domain in CS and Ae. peregrina, but neither site was phosphorylated in Bd21, suggesting GBSSI phosphorylation could improve amylose biosynthesis. Bd21 contains only B-granules, and the expression of key genes in the three studied genera is consistent with the dynamic development of starch granules. GBSSI is present in greater amounts in the B-granules of CS than in Bd21; two phosphorylation sites (Thr183 and Tyr185) were found in Triticum and Aegilops; these sites were not phosphorylated in Bd21. GBSSI phosphorylation may reflect its importance in amylose synthesis.

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

    Science.gov (United States)

    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...

  3. Constitutive protein secretion from the exocrine pancreas of fetal rats

    International Nuclear Information System (INIS)

    Arvan, P.; Chang, A.

    1987-01-01

    Two general kinds of exocytotic secretion of proteins are known: that which is stimulated by secretagogues; and constitutive exocytosis, which is unable to be stimulated. The exocrine pancreas has often been cited as a model system for the first kind of secretion. However, the release of digestive enzymes from the exocrine pancreas of 1-day prenatal rats cannot be stimulated by secretagogues; therefore, its secretion is constitutive. To gain insight into the intracellular pathways which mediate secretion in the fetal gland, we examined the kinetics of release of newly synthesized proteins. We find that fetal pancreas in a steady state of secretion releases pulse-labeled secretory proteins in two kinetically distinct phases. The first phase occurring during 0-6.5 h of chase comprises approximately 12% of total incorporated radioactivity, the second phase beginning at greater than 7 h of chase comprises the remainder. Based on analysis by electron microscope autoradiography, radiolabel is localized during the first phase of secretion in immature granules/condensing vacuoles, Golgi compartments, and few mature granules. The second phase of secretion occurs when radiolabel is predominantly in mature granules. We propose that secretion occurs via (at least) 2 exocytotic routes, both of which are constitutive in fetal pancreatic tissue

  4. Photoautotrophic Polyhydroxybutyrate Granule Formation Is Regulated by Cyanobacterial Phasin PhaP in Synechocystis sp. Strain PCC 6803

    Science.gov (United States)

    Hauf, Waldemar; Watzer, Björn; Roos, Nora; Klotz, Alexander

    2015-01-01

    Cyanobacteria are photoautotrophic microorganisms which fix atmospheric carbon dioxide via the Calvin-Benson cycle to produce carbon backbones for primary metabolism. Fixed carbon can also be stored as intracellular glycogen, and in some cyanobacterial species like Synechocystis sp. strain PCC 6803, polyhydroxybutyrate (PHB) accumulates when major nutrients like phosphorus or nitrogen are absent. So far only three enzymes which participate in PHB metabolism have been identified in this organism, namely, PhaA, PhaB, and the heterodimeric PHB synthase PhaEC. In this work, we describe the cyanobacterial PHA surface-coating protein (phasin), which we term PhaP, encoded by ssl2501. Translational fusion of Ssl2501 with enhanced green fluorescent protein (eGFP) showed a clear colocalization to PHB granules. A deletion of ssl2501 reduced the number of PHB granules per cell, whereas the mean PHB granule size increased as expected for a typical phasin. Although deletion of ssl2501 had almost no effect on the amount of PHB, the biosynthetic activity of PHB synthase was negatively affected. Secondary-structure prediction and circular dichroism (CD) spectroscopy of PhaP revealed that the protein consists of two α-helices, both of them associating with PHB granules. Purified PhaP forms oligomeric structures in solution, and both α-helices of PhaP contribute to oligomerization. Together, these results support the idea that Ssl2501 encodes a cyanobacterial phasin, PhaP, which regulates the surface-to-volume ratio of PHB granules. PMID:25911471

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

    Science.gov (United States)

    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. Published by Elsevier Ltd.

  6. RhoG protein regulates platelet granule secretion and thrombus formation in mice.

    Science.gov (United States)

    Goggs, Robert; Harper, Matthew T; Pope, Robert J; Savage, Joshua S; Williams, Christopher M; Mundell, Stuart J; Heesom, Kate J; Bass, Mark; Mellor, Harry; Poole, Alastair W

    2013-11-22

    Rho GTPases such as Rac, RhoA, and Cdc42 are vital for normal platelet function, but the role of RhoG in platelets has not been studied. In other cells, RhoG orchestrates processes integral to platelet function, including actin cytoskeletal rearrangement and membrane trafficking. We therefore hypothesized that RhoG would play a critical role in platelets. Here, we show that RhoG is expressed in human and mouse platelets and is activated by both collagen-related peptide (CRP) and thrombin stimulation. We used RhoG(-/-) mice to study the function of RhoG in platelets. Integrin activation and aggregation were reduced in RhoG(-/-) platelets stimulated by CRP, but responses to thrombin were normal. The central defect in RhoG(-/-) platelets was reduced secretion from α-granules, dense granules, and lysosomes following CRP stimulation. The integrin activation and aggregation defects could be rescued by ADP co-stimulation, indicating that they are a consequence of diminished dense granule secretion. Defective dense granule secretion in RhoG(-/-) platelets limited recruitment of additional platelets to growing thrombi in flowing blood in vitro and translated into reduced thrombus formation in vivo. Interestingly, tail bleeding times were normal in RhoG(-/-) mice, suggesting that the functions of RhoG in platelets are particularly relevant to thrombotic disorders.

  7. [Change of peripheral blood appetite regulation factor of anorexia children and infect of child anorexia granule].

    Science.gov (United States)

    Hu, Ai-Hua; Xu, Hui-Min; Hu, Guo-Hua; Jin, Fang; Li, Zhong; Fang, Guo-Xing

    2014-12-01

    Study the infect of child anorexia granule on serum ghrelin and leptin of anorexia children and its clinical efficacy. Selected 81 cases of anorexia children aged 1-6 years old into treatment group (42 cases) and control group (39 cases), in addition, 30 case healthy children as healthy control group. The control group children were treated with domperidone suspension 0.3 mg x kg(-1) x d(-1), tid, orally 30 minutes before meals. Treatment group were treated with child anorexia granule, 1-3 years 1 package, bid; 4-6 years 1 package, tid; po, 4 weeks as a course of treatment. Study the change of serum ghrelin and leptin before and after therapy. The study demonstrates that before treatment, the serum ghrelin level of disease group was lower than healthy group (P anorexia granule can facilitate secretion of ghrelin, and inhibit secretion of leptin, so as to work up an appetite. And the molecular mechanism is its infect on serum ghrelin, leptin.

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

    International Nuclear Information System (INIS)

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

    1988-01-01

    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 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 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

  9. CXCL12-mediated feedback from granule neurons regulates generation and positioning of new neurons in the dentate gyrus.

    Science.gov (United States)

    Abe, Philipp; Wüst, Hannah M; Arnold, Sebastian J; van de Pavert, Serge A; Stumm, Ralf

    2018-03-14

    Adult hippocampal neurogenesis is implicated in learning and memory processing. It is tightly controlled at several levels including progenitor proliferation as well as migration, differentiation and integration of new neurons. Hippocampal progenitors and immature neurons reside in the subgranular zone (SGZ) and are equipped with the CXCL12-receptor CXCR4 which contributes to defining the SGZ as neurogenic niche. The atypical CXCL12-receptor CXCR7 functions primarily by sequestering extracellular CXCL12 but whether CXCR7 is involved in adult neurogenesis has not been assessed. We report that granule neurons (GN) upregulate CXCL12 and CXCR7 during dentate gyrus maturation in the second postnatal week. To test whether GN-derived CXCL12 regulates neurogenesis and if neuronal CXCR7 receptors influence this process, we conditionally deleted Cxcl12 and Cxcr7 from the granule cell layer. Cxcl12 deletion resulted in lower numbers, increased dispersion and abnormal dendritic growth of immature GN and reduced neurogenesis. Cxcr7 ablation caused an increase in progenitor proliferation and progenitor numbers and reduced dispersion of immature GN. Thus, we provide a new mechanism where CXCL12-signals from GN prevent dispersion and support maturation of newborn GN. CXCR7 receptors of GN modulate the CXCL12-mediated feedback from GN to the neurogenic niche. © 2018 Wiley Periodicals, Inc.

  10. The histone demethylase Kdm6b regulates a mature gene expression program in differentiating cerebellar granule neurons.

    Science.gov (United States)

    Wijayatunge, Ranjula; Liu, Fang; Shpargel, Karl B; Wayne, Nicole J; Chan, Urann; Boua, Jane-Valeriane; Magnuson, Terry; West, Anne E

    2018-03-01

    The histone H3 lysine 27 (H3K27) demethylase Kdm6b (Jmjd3) can promote cellular differentiation, however its physiological functions in neurons remain to be fully determined. We studied the expression and function of Kdm6b in differentiating granule neurons of the developing postnatal mouse cerebellum. At postnatal day 7, Kdm6b is expressed throughout the layers of the developing cerebellar cortex, but its expression is upregulated in newborn cerebellar granule neurons (CGNs). Atoh1-Cre mediated conditional knockout of Kdm6b in CGN precursors either alone or in combination with Kdm6a did not disturb the gross morphological development of the cerebellum. Furthermore, RNAi-mediated knockdown of Kdm6b in cultured CGN precursors did not alter the induced expression of early neuronal marker genes upon cell cycle exit. By contrast, knockdown of Kdm6b significantly impaired the induction of a mature neuronal gene expression program, which includes gene products required for functional synapse maturation. Loss of Kdm6b also impaired the ability of Brain-Derived Neurotrophic Factor (BDNF) to induce expression of Grin2c and Tiam1 in maturing CGNs. Taken together, these data reveal a previously unknown role for Kdm6b in the postmitotic stages of CGN maturation and suggest that Kdm6b may work, at least in part, by a transcriptional mechanism that promotes gene sensitivity to regulation by BDNF. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. ANGUSTIFOLIA, a Plant Homolog of CtBP/BARS Localizes to Stress Granules and Regulates Their Formation

    Directory of Open Access Journals (Sweden)

    Hemal Bhasin

    2017-06-01

    Full Text Available The ANGUSTIFOLIA (AN gene in Arabidopsis is important for a plethora of morphological phenotypes. Recently, AN was also reported to be involved in responses to biotic and abiotic stresses. It encodes a homolog of the animal C-terminal binding proteins (CtBPs. In contrast to animal CtBPs, AN does not appear to function as a transcriptional co-repressor and instead functions outside nucleus where it might be involved in Golgi-associated membrane trafficking. In this study, we report a novel and unexplored role of AN as a component of stress granules (SGs. Interaction studies identified several RNA binding proteins that are associated with AN. AN co-localizes with several messenger ribonucleoprotein granule markers to SGs in a stress dependent manner. an mutants exhibit an altered SG formation. We provide evidence that the NAD(H binding domain of AN is relevant in this context as proteins carrying mutations in this domain localize to a much higher degree to SGs and strongly reduce AN dimerization and its interaction with one interactor but not the others. Finally, we show that AN is a negative regulator of salt and osmotic stress responses in Arabidopsis suggesting a functional relevance in SGs.

  12. The F-actin modifier villin regulates insulin granule dynamics and exocytosis downstream of islet cell autoantigen 512

    Directory of Open Access Journals (Sweden)

    Hassan Mziaut

    2016-08-01

    Full Text Available Objective: Insulin release from pancreatic islet β cells should be tightly controlled to avoid hypoglycemia and insulin resistance. The cortical actin cytoskeleton is a gate for regulated exocytosis of insulin secretory granules (SGs by restricting their mobility and access to the plasma membrane. Prior studies suggest that SGs interact with F-actin through their transmembrane cargo islet cell autoantigen 512 (Ica512 (also known as islet antigen 2/Ptprn. Here we investigated how Ica512 modulates SG trafficking and exocytosis. Methods: Transcriptomic changes in Ica512−/− mouse islets were analyzed. Imaging as well as biophysical and biochemical methods were used to validate if and how the Ica512-regulated gene villin modulates insulin secretion in mouse islets and insulinoma cells. Results: The F-actin modifier villin was consistently downregulated in Ica512−/− mouse islets and in Ica512-depleted insulinoma cells. Villin was enriched at the cell cortex of β cells and dispersed villin−/− islet cells were less round and less deformable. Basal mobility of SGs in villin-depleted cells was enhanced. Moreover, in cells depleted either of villin or Ica512 F-actin cages restraining cortical SGs were enlarged, basal secretion was increased while glucose-stimulated insulin release was blunted. The latter changes were reverted by overexpressing villin in Ica512-depleted cells, but not vice versa. Conclusion: Our findings show that villin controls the size of the F-actin cages restricting SGs and, thus, regulates their dynamics and availability for exocytosis. Evidence that villin acts downstream of Ica512 also indicates that SGs directly influence the remodeling properties of the cortical actin cytoskeleton for tight control of insulin secretion. Keywords: F-actin, Granules, Ica512, Insulin, Secretion, Villin

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

    Directory of Open Access Journals (Sweden)

    Anita Giglio

    2011-05-01

    Full Text Available 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.

  14. Is there adaptation of the exocrine pancreas in wild animal? The case of the Roe Deer

    OpenAIRE

    Guilloteau, Paul; Vitari, Francesca; Meuth, Valérie Metzinger-Le; Le Normand, Laurence; Romé, Véronique; Savary, Gérard; Delaby, Luc; Domeneghini, Cinzia; Morisset, Jean

    2012-01-01

    Abstract Background Physiology of the exocrine pancreas has been well studied in domestic and in laboratory animals as well as in humans. However, it remains quite unknown in wildlife mammals. Roe deer and cattle (including calf) belong to different families but have a common ancestor. This work aimed to evaluate in the Roe deer, the adaptation to diet of the exocrine pancreatic functions and regulations related to animal evolution and domestication. Results Forty bovine were distributed into...

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

    Science.gov (United States)

    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.

  16. Cdk5 regulates accurate maturation of newborn granule cells in the adult hippocampus.

    Directory of Open Access Journals (Sweden)

    Sebastian Jessberger

    2008-11-01

    Full Text Available Newborn granule cells become functionally integrated into the synaptic circuitry of the adult dentate gyrus after a morphological and electrophysiological maturation process. The molecular mechanisms by which immature neurons and the neurites extending from them find their appropriate position and target area remain largely unknown. Here we show that single-cell-specific knockdown of cyclin-dependent kinase 5 (cdk5 activity in newborn cells using a retrovirus-based strategy leads to aberrant growth of dendritic processes, which is associated with an altered migration pattern of newborn cells. Even though spine formation and maturation are reduced in cdk5-deficient cells, aberrant dendrites form ectopic synapses onto hilar neurons. These observations identify cdk5 to be critically involved in the maturation and dendrite extension of newborn neurons in the course of adult neurogenesis. The data presented here also suggest a mechanistic dissociation between accurate dendritic targeting and subsequent synapse formation.

  17. The life cycle of platelet granules.

    Science.gov (United States)

    Sharda, Anish; Flaumenhaft, Robert

    2018-01-01

    Platelet granules are unique among secretory vesicles in both their content and their life cycle. Platelets contain three major granule types-dense granules, α-granules, and lysosomes-although other granule types have been reported. Dense granules and α-granules are the most well-studied and the most physiologically important. Platelet granules are formed in large, multilobulated cells, termed megakaryocytes, prior to transport into platelets. The biogenesis of dense granules and α-granules involves common but also distinct pathways. Both are formed from the trans -Golgi network and early endosomes and mature in multivesicular bodies, but the formation of dense granules requires trafficking machinery different from that of α-granules. Following formation in the megakaryocyte body, both granule types are transported through and mature in long proplatelet extensions prior to the release of nascent platelets into the bloodstream. Granules remain stored in circulating platelets until platelet activation triggers the exocytosis of their contents. Soluble N -ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins, located on both the granules and target membranes, provide the mechanical energy that enables membrane fusion during both granulogenesis and exocytosis. The function of these core fusion engines is controlled by SNARE regulators, which direct the site, timing, and extent to which these SNAREs interact and consequently the resulting membrane fusion. In this review, we assess new developments in the study of platelet granules, from their generation to their exocytosis.

  18. Mathematical modeling and statistical analysis of calcium-regulated insulin granule exocytosis in ß-cells from mice and humans

    DEFF Research Database (Denmark)

    Pedersen, Morten Gram; Cortese, Giuliana; Eliasson, Lena

    2011-01-01

    Insulin is released from pancreatic ß-cells as a result of Ca2+-evoked exocytosis of dense-core granules. Secretion is biphasic, which has been suggested to correspond to the release of different granule pools. Here we review and carefully reanalyze previously published patch-clamp data on depola......Insulin is released from pancreatic ß-cells as a result of Ca2+-evoked exocytosis of dense-core granules. Secretion is biphasic, which has been suggested to correspond to the release of different granule pools. Here we review and carefully reanalyze previously published patch-clamp data...... on depolarization-evoked Ca2+-currents and corresponding capacitance measurements. Using a statistical mixed-effects model, we show that the data indicate that pool depletion is negligible in response to short depolarizations in mouse ß-cells. We then review mathematical models of granule dynamics and exocytosis...

  19. Vacuolization of mucolipidosis type II mouse exocrine gland cells represents accumulation of autolysosomes.

    Science.gov (United States)

    Boonen, Marielle; van Meel, Eline; Oorschot, Viola; Klumperman, Judith; Kornfeld, Stuart

    2011-04-15

    We previously reported that mice deficient in UDP-GlcNAc:lysosomal enzyme GlcNAc-1-phosphotransferase (mucolipidosis type II or Gnptab -/- mice), the enzyme that initiates the addition of the mannose 6-phosphate lysosomal sorting signal on acid hydrolases, exhibited extensive vacuolization of their exocrine gland cells, while the liver, brain, and muscle appeared grossly unaffected. Similar pathological findings were observed in several exocrine glands of patients with mucolipidosis II. To understand the basis for this cell type-specific abnormality, we analyzed these tissues in Gnptab -/- mice using a combined immunoelectron microscopy and biochemical approach. We demonstrate that the vacuoles in the exocrine glands are enlarged autolysosomes containing undigested cytoplasmic material that accumulate secondary to deficient lysosomal function. Surprisingly, the acid hydrolase levels in these tissues ranged from normal to modestly decreased, in contrast to skin fibroblasts, which accumulate enlarged lysosomes and/or autolysosomes also but exhibit very low levels of acid hydrolases. We propose that the lysosomal defect in the exocrine cells is caused by the combination of increased secretion of the acid hydrolases via the constitutive pathway along with their entrapment in secretory granules. Taken together, our results provide new insights into the mechanisms of the tissue-specific abnormalities seen in mucolipidosis type II.

  20. Casein Kinase 1δ Is an APC/CCdh1 Substrate that Regulates Cerebellar Granule Cell Neurogenesis

    Directory of Open Access Journals (Sweden)

    Clara Penas

    2015-04-01

    Full Text Available Although casein kinase 1δ (CK1δ is at the center of multiple signaling pathways, its role in the expansion of CNS progenitor cells is unknown. Using mouse cerebellar granule cell progenitors (GCPs as a model for brain neurogenesis, we demonstrate that the loss of CK1δ or treatment of GCPs with a highly selective small molecule inhibits GCP expansion. In contrast, CK1δ overexpression increases GCP proliferation. Thus, CK1δ appears to regulate GCP neurogenesis. CK1δ is targeted for proteolysis via the anaphase-promoting complex/cyclosome (APC/CCdh1 ubiquitin ligase, and conditional deletion of the APC/CCdh1 activator Cdh1 in cerebellar GCPs results in higher levels of CK1δ. APC/CCdh1 also downregulates CK1δ during cell-cycle exit. Therefore, we conclude that APC/CCdh1 controls CK1δ levels to balance proliferation and cell-cycle exit in the developing CNS. Similar studies in medulloblastoma cells showed that CK1δ holds promise as a therapeutic target.

  1. TIA-1 Self-Multimerization, Phase Separation, and Recruitment into Stress Granules Are Dynamically Regulated by Zn2.

    Science.gov (United States)

    Rayman, Joseph B; Karl, Kevin A; Kandel, Eric R

    2018-01-02

    Stress granules are non-membranous structures that transiently form in the cytoplasm during cellular stress, where they promote translational repression of non-essential RNAs and modulate cell signaling by sequestering key signal transduction proteins. These and other functions of stress granules facilitate an adaptive cellular response to environmental adversity. A key component of stress granules is the prion-related RNA-binding protein, T cell intracellular antigen-1 (TIA-1). Here, we report that recombinant TIA-1 undergoes rapid multimerization and phase separation in the presence of divalent zinc, which can be reversed by the zinc chelator, TPEN. Similarly, the formation and maintenance of TIA-1-positive stress granules in arsenite-treated cells are inhibited by TPEN. In addition, Zn 2+ is released in cells treated with arsenite, before stress granule formation. These findings suggest that Zn 2+ is a physiological ligand of TIA-1, acting as a stress-inducible second messenger to promote multimerization of TIA-1 and subsequent localization into stress granules. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  2. A comparative study of the ultrastructure of submandibular, parotid and exocrine pancreas in diabetes and fasting

    International Nuclear Information System (INIS)

    Take, G.; Ilgaz, C.; Erdogan, D.; Ozogul, C.; Elmas, C.

    2007-01-01

    To comparatively analyze the ultrastructural changes in the submandibular and parotid glands and in the exocrine pancreas following diabetes induced by Streptozotocin exposure and the effects of fasting and insulin treatment on these alterations. For experimental procedure, we included 48 Sprague-Dawley type rats in July 2001-March 2002 at Gazi University, Turkey. We divided the rats into 8 groups following the infusion of Streptozotocin. While the degeneration manifested itself as accumulation of secretions within the mucous cells in the submandibular gland, lipid droplets were absent, being replaced by vacuolar structures. The parotid gland and exocrine pancreas, having similar properties, were affected similarly. Diabetes-induced loss of granules was observed in the serous cells in both glands. There was diffuse lipid accumulation within these cells. Regarding granule content, we observed the most prominent degenerative changes in the parotid gland. While cellular loss was observed in neither the submandibular, nor the parotid gland, we noted presence of apoptotic cells was noted in the pancreas. State of fasting was found to cause alterations within the glands indicating increased activity. While insulin treatment was seen to restore the structure to normal in general was in both of the 3 glands. This study demonstrated that both of the 3 glands are affected by diabetes and concomitant fasting, and this effect manifests itself via the granule content. (author)

  3. Pancreatic Exocrine Insufficiency in Pancreatic Cancer.

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

    Hashimoto, Osamu; Ushiro, Yuuki; Sekiyama, Kazunari; Yamaguchi, Osamu; Yoshioka, Kazuki; Mutoh, Ken-Ichiro; Hasegawa, Yoshihisa

    2006-01-01

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

  5. Hepatitis C virus (HCV) induces formation of stress granules whose proteins regulate HCV RNA replication and virus assembly and egress.

    Science.gov (United States)

    Garaigorta, Urtzi; Heim, Markus H; Boyd, Bryan; Wieland, Stefan; Chisari, Francis V

    2012-10-01

    Stress granules (SGs) are cytoplasmic structures that are induced in response to environmental stress, including viral infections. Here we report that hepatitis C virus (HCV) triggers the appearance of SGs in a PKR- and interferon (IFN)-dependent manner. Moreover, we show an inverse correlation between the presence of stress granules and the induction of IFN-stimulated proteins, i.e., MxA and USP18, in HCV-infected cells despite high-level expression of the corresponding MxA and USP18 mRNAs, suggesting that interferon-stimulated gene translation is inhibited in stress granule-containing HCV-infected cells. Finally, in short hairpin RNA (shRNA) knockdown experiments, we found that the stress granule proteins T-cell-restricted intracellular antigen 1 (TIA-1), TIA1-related protein (TIAR), and RasGAP-SH3 domain binding protein 1 (G3BP1) are required for efficient HCV RNA and protein accumulation at early time points in the infection and that G3BP1 and TIA-1 are required for intracellular and extracellular infectious virus production late in the infection, suggesting that they are required for virus assembly. In contrast, TIAR downregulation decreases extracellular infectious virus titers with little effect on intracellular RNA content or infectivity late in the infection, suggesting that it is required for infectious particle release. Collectively, these results illustrate that HCV exploits the stress granule machinery at least two ways: by inducing the formation of SGs by triggering PKR phosphorylation, thereby downregulating the translation of antiviral interferon-stimulated genes, and by co-opting SG proteins for its replication, assembly, and egress.

  6. Adiponectin regulates contextual fear extinction and intrinsic excitability of dentate gyrus granule neurons through AdipoR2 receptors.

    Science.gov (United States)

    Zhang, D; Wang, X; Wang, B; Garza, J C; Fang, X; Wang, J; Scherer, P E; Brenner, R; Zhang, W; Lu, X-Y

    2017-07-01

    Post-traumatic stress disorder (PTSD) is characterized by exaggerated fear expression and impaired fear extinction. The underlying molecular and cellular mechanisms of PTSD are largely unknown. The current pharmacological and non-pharmacological treatments for PTSD are either ineffective or temporary with high relapse rates. Here we report that adiponectin-deficient mice exhibited normal contextual fear conditioning but displayed slower extinction learning. Infusions of adiponectin into the dentate gyrus (DG) of the hippocampus in fear-conditioned mice facilitated extinction of contextual fear. Whole-cell patch-clamp recordings in brain slices revealed that intrinsic excitability of DG granule neurons was enhanced by adiponectin deficiency and suppressed after treatment with the adiponectin mimetic AdipoRon, which were associated with increased input resistance and hyperpolarized resting membrane potential, respectively. Moreover, deletion of AdipoR2, but not AdipoR1 in the DG, resulted in augmented fear expression and reduced extinction, accompanied by intrinsic hyperexcitability of DG granule neurons. Adiponectin and AdipoRon failed to induce facilitation of fear extinction and elicit inhibition of intrinsic excitability of DG neurons in AdipoR2 knockout mice. These results indicated that adiponectin action via AdipoR2 was both necessary and sufficient for extinction of contextual fear and intrinsic excitability of DG granule neurons, implying that enhancing or dampening DG neuronal excitability may cause resistance to or facilitation of extinction. Therefore, our findings provide a functional link between adiponectin/AdipoR2 activation, DG neuronal excitability and contextual fear extinction, and suggest that targeting adiponectin/AdipoR2 may be used to strengthen extinction-based exposure therapies for PTSD.

  7. Time-regulated drug delivery system based on coaxially incorporated platelet alpha-granules for biomedical use

    Czech Academy of Sciences Publication Activity Database

    Buzgo, Matej; Jakubová, Radka; Míčková, Andrea; Rampichová, Michala; Prosecká, Eva; Kochová, P.; Lukáš, D.; Amler, Evžen

    2013-01-01

    Roč. 8, č. 7 (2013), s. 1137-1154 ISSN 1743-5889 R&D Projects: GA ČR GAP304/10/1307 Grant - others:GA UK(CZ) 330611; GA UK(CZ) 384311; GA UK(CZ) 626012; GA MŠk(CZ) ME10145; GA MZd(CZ) NT12156 Institutional research plan: CEZ:AV0Z50390703; CEZ:AV0Z50390512 Keywords : Core-shell nanofibers * alpha granules * cartilage tissue engineering Subject RIV: FP - Other Medical Disciplines Impact factor: 5.824, year: 2013

  8. Pancreatic exocrine secretion in atomic bomb survivors

    International Nuclear Information System (INIS)

    Hiraoka, Masataka; Kawanishi, Masahiro; Ohtaki, Megu

    1989-01-01

    This study was designed to examine the effect of A-bombing on pancreatic exocrine secretion in 6 A-bomb survivors (an average age of 57 years) and the age- and sex-matched non-exposed 6 persons (an average age of 58 years). Six A-bomb survivors consisted of: three who had been directly exposed to A-bombing, one who had entered the city within 3 days after bombing, one who had worked in caring for A-bomb survivors, and one who had later entered the city. Caerulein-Secretin test revealed no significant difference in the total secretion of lipase, maximum bicarbonate, amylase output, or lipase output between the exposed and non-exposed groups. The concentration of lipase ten min after stimulation was significantly decreased in the exposed group than the control group. This suggests that radiation may be responsible for abnormality in the ability of pancreatic exocrine secretion. (N.K.)

  9. Pancreatic Exocrine Insufficiency in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Miroslav Vujasinovic

    2017-02-01

    Full Text Available 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.

  10. The type II cGMP dependent protein kinase regulates GluA1 levels at the plasma membrane of developing cerebellar granule cells

    Science.gov (United States)

    Incontro, Salvatore; Ciruela, Francisco; Ziff, Edward; Hofmann, Franz; Sánchez-Prieto, José; Torres, Magdalena

    2014-01-01

    Trafficking of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) is regulated by specific interactions with other proteins and by post-translational mechanisms, such as phosphorylation. We have found that the type II cGMP-dependent protein kinase (cGKII) phosphorylates GluA1 (formerly GluR1) at S845, augmenting the surface expression of AMPARs at both synaptic and extrasynaptic sites. Activation of cGKII by 8-Br-cGMP enhances the surface expression of GluA1, whereas its inhibition or suppression effectively diminished the expression of this protein at the cell surface. In granule cells, NMDA receptor activation (NMDAR) stimulates nitric oxide and cGMP production, which in turn activates cGKII and induces the phosphorylation of GluA1, promoting its accumulation in the plasma membrane. GluA1 is mainly incorporated into calcium permeable AMPARs as exposure to 8-Br-cGMP or NMDA activation enhanced AMPA-elicited calcium responses that are sensitive to NASPM inhibition. We summarize evidence for an increase of calcium permeable AMPA receptors downstream of NMDA receptor activation that might be relevant for granule cell development and plasticity. PMID:23545413

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

    Science.gov (United States)

    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.

  12. Diagnosis and management of pancreatic exocrine insufficiency.

    Science.gov (United States)

    Nikfarjam, Mehrdad; Wilson, Jeremy S; Smith, Ross C

    2017-08-21

    In 2015, the Australasian Pancreatic Club (APC) published the Australasian guidelines for the management of pancreatic exocrine insufficiency (http://pancreas.org.au/2016/01/pancreatic-exocrine-insufficiency-guidelines). Pancreatic exocrine insufficiency (PEI) occurs when normal digestion cannot be sustained due to insufficient pancreatic digestive enzyme activity. This may be related to a breakdown, at any point, in the pancreatic digestive chain: pancreatic stimulation; synthesis, release or transportation of pancreatic enzymes; or synchronisation of secretions to mix with ingested food. Main recommendations: The guidelines provide advice on diagnosis and management of PEI, noting the following: A high prevalence of PEI is seen in certain diseases and conditions, such as cystic fibrosis, acute and chronic pancreatitis, pancreatic cancer and pancreatic surgery. The main symptoms of PEI are steatorrhoea or diarrhoea, abdominal pain, bloating and weight loss. These symptoms are non-specific and often go undetected and untreated. PEI diagnosis is predominantly based on clinical findings and the presence of underlying disease. The likelihood of PEI in suspected patients has been categorised into three groups: definite, possible and unlikely. If left untreated, PEI may lead to complications related to fat malabsorption and malnutrition, and have an impact on quality of life. Pancreatic enzyme replacement therapy (PERT) remains the mainstay of PEI treatment with the recommended adult initial enzyme dose being 25 000-40 000 units of lipase per meal, titrating up to a maximum of 75 000-80 000 units of lipase per meal. Adjunct acid-suppressing therapy may be useful when patients still experience symptoms of PEI on high dose PERT. Nutritional management by an experienced dietitian is essential. Changes in management as a result of these guidelines: These are the first guidelines to classify PEI as being definite, possible or unlikely, and provide a diagnostic algorithm to

  13. Neurotrophin and FGF Signaling Adapter Proteins, FRS2 and FRS3, Regulate Dentate Granule Cell Maturation and Excitatory Synaptogenesis.

    Science.gov (United States)

    Nandi, Sayan; Alviña, Karina; Lituma, Pablo J; Castillo, Pablo E; Hébert, Jean M

    2018-01-15

    Dentate granule cells (DGCs) play important roles in cognitive processes. Knowledge about how growth factors such as FGFs and neurotrophins contribute to the maturation and synaptogenesis of DGCs is limited. Here, using brain-specific and germline mouse mutants we show that a module of neurotrophin and FGF signaling, the FGF Receptor Substrate (FRS) family of intracellular adapters, FRS2 and FRS3, are together required for postnatal brain development. In the hippocampus, FRS promotes dentate gyrus morphogenesis and DGC maturation during developmental neurogenesis, similar to previously published functions for both neurotrophins and FGFs. Consistent with a role in DGC maturation, two-photon imaging revealed that Frs2,3-double mutants have reduced numbers of dendritic branches and spines in DGCs. Functional analysis further showed that double-mutant mice exhibit fewer excitatory synaptic inputs onto DGCs. These observations reveal roles for FRS adapters in DGC maturation and synaptogenesis and suggest that FRS proteins may act as an important node for FGF and neurotrophin signaling in postnatal hippocampal development. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Maria J Lima

    Full Text Available 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.

  15. Staging chronic pancreatitis with exocrine function tests: Are we better?

    Science.gov (United States)

    Sperti, Cosimo; Moletta, Lucia

    2017-10-14

    Chronic pancreatitis (CP) is an inflammatory disease of the pancreas evolving in progressive fibrotic disruption of the gland with exocrine and endocrine pancreatic insufficiency. Although imaging features of CP are well known, their correlation with exocrine pancreatic function tests are not obvious, particularly in the early stage of the disease. There are many clinical classification of CP, all suggested for better distinguish and manage different forms based on etiological and clinical factors, and severity of the disease. Recently, a new classification of CP has been suggested: the M-ANNHEIM multiple risk factor classification that includes etiology, stage classification and degree of clinical severity. However, more accurate determination of clinical severity of CP requires a correct determination of exocrine function of the pancreas and fecal fat excretion. Recently, Kamath et al demonstrated that the evaluation of exocrine pancreatic function by acid steatocrit and fecal elastase-1 (EF-1) was helpful, but EF-1 was able to detect exocrine pancreatic insufficiency in more patients, upgrading some patients in higher stage of disease according to M-ANNHEIM classification. So, EF-1 is a more accurate test to determine exocrine pancreatic insufficiency and to stage chronic pancreatitis in the M-ANNHEIM classification. On the contrary, EF-1 determination shows low sensitivity in detecting exocrine pancreatic insufficiency in early stage of the disease.

  16. Extracellular ATP in the Exocrine Pancreas – ATP Release, Signalling and Metabolism

    DEFF Research Database (Denmark)

    Kowal, Justyna Magdalena

    release. So far, the contribution of duct cells in purinergic signalling has never been studied. This work presents that both acinar and duct cells are sources of extracellular ATP in the exocrine pancreas. Here we show that duct cells release ATP in response to several physiological......ATP plays an important role as an autocrine/paracrine signalling molecule, being released from a number of tissues, in response to physiological and pathophysiological stimuli. Released ATP induces Ca2+ - and/or cAMP - dependent cellular responses via activation of ubiquitously expressed P2X and P2......, particularly during Ca2+ stress conditions. In conclusion, these studies demonstrate a complex regulation of purinergic signalling in exocrine pancreas. A crucial role for duct cells in mediating extracellular nucleotides homeostasis, involving ATP release, subsequent hydrolysis and conversion via...

  17. Relationship between the exocrine and endocrine pancreas after acute pancreatitis.

    Science.gov (United States)

    Das, Stephanie L M; Kennedy, James I C; Murphy, Rinki; Phillips, Anthony R J; Windsor, John A; Petrov, Maxim S

    2014-12-07

    To determine the prevalence and time course of pancreatic exocrine insufficiency in individuals with newly diagnosed prediabetes or diabetes mellitus after acute pancreatitis. Relevant literature cited in three major biomedical journal databases (EMBASE, MEDLINE, and Scopus) was reviewed independently by two authors. There were no language constraints but the search was limited to human studies. Studies included were cohort studies of adult patients who were discharged after an attack of acute pancreatitis. Patients were excluded if they were under 18 years of age or had a previous diagnosis of prediabetes or diabetes mellitus, pancreatic exocrine insufficiency, or chronic pancreatitis. The main outcome measure was the prevalence of concomitant pancreatic exocrine insufficiency in patients who were diagnosed with prediabetes and diabetes mellitus after an attack of acute pancreatitis. Subgroup analysis was conducted for patients who were diagnosed with prediabetes only and those who were diagnosed with diabetes mellitus only. Subgroup analysis looking at the time course of concomitant pancreatic exocrine and endocrine insufficiency was also conducted. Pooled prevalence and corresponding 95% confidence intervals were calculated for all outcome measures and P-values pancreatitis was 43% (95%CI: 30%-56%). The pooled prevalence of pancreatic exocrine insufficiency in individuals after acute pancreatitis was 29% (95%CI: 19%-39%). The prevalence of concomitant pancreatic exocrine insufficiency in individuals with newly diagnosed prediabetes or diabetes was 40% (95%CI: 25%-55%). The prevalence of concomitant pancreatic exocrine insufficiency among individuals with prediabetes alone and diabetes mellitus alone was 41% (95%CI: 12%-75%) and 39% (95%CI: 28%-51%), respectively. Further analysis showed that the prevalence of concomitant pancreatic exocrine insufficiency in individuals with prediabetes or diabetes decreases over time after an attack of acute pancreatitis

  18. Purinergic receptors in the endocrine and exocrine pancreas

    DEFF Research Database (Denmark)

    Novak, I

    2008-01-01

    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......, there is also evidence for other P2 and adenosine receptors in beta cells (P2Y(2), P2Y(4), P2Y(6), P2X subtypes and A(1) receptors) and in glucagon-secreting alpha cells (P2X(7), A(2) receptors). In the exocrine pancreas, acini release ATP and ATP-hydrolysing and ATP-generating enzymes. P2 receptors...

  19. Pheromones and exocrine glands in Isoptera.

    Science.gov (United States)

    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.

  20. Dynamics of starch granule biogenesis - the role of redox-regulated enzymes and low-affinity carbohydrate-binding modules

    DEFF Research Database (Denmark)

    Blennow, A.; Svensson, Birte

    2010-01-01

    The deposition and degradation of starch in plants is subject to extensive post-translational regulation. To permit degradation of B-type crystallites present in tuberous and leaf starch these starch types are phosphorylated by glucan, water dikinase (GWD). At the level of post-translational redo...

  1. Nuclear receptor 4a3 (nr4a3 regulates murine mast cell responses and granule content.

    Directory of Open Access Journals (Sweden)

    Gianni Garcia-Faroldi

    Full Text Available Nuclear receptor 4a3 (Nr4a3 is a transcription factor implicated in various settings such as vascular biology and inflammation. We have recently shown that mast cells dramatically upregulate Nuclear receptor 4a3 upon activation, and here we investigated the functional impact of Nuclear receptor 4a3 on mast cell responses. We show that Nuclear receptor 4a3 is involved in the regulation of cytokine/chemokine secretion in mast cells following activation via the high affinity IgE receptor. Moreover, Nuclear receptor 4a3 negatively affects the transcript and protein levels of mast cell tryptase as well as the mast cell's responsiveness to allergen. Together, these findings identify Nuclear receptor 4a3 as a novel regulator of mast cell function.

  2. Morphology and diversity of exocrine glands in lepidopteran larvae.

    Science.gov (United States)

    Vegliante, Francesca; Hasenfuss, Ivar

    2012-01-01

    The morphology of 21 exocrine glands and 13 supposedly exocrine structures recorded for lepidopteran larvae is reviewed. The epitracheal glands, for which a double role (exocrine and endocrine) has been demonstrated, are examined as well. Function is well known for at least 8 glands but completely unknown for 6 glands, for 10 putative glandular structures, and for the exocrine component of the epitracheal glands. Functional studies on the remaining structures are insufficient; in some cases (mandibular gland and adenosma) homologous glands may play a different role depending on the species, and only a few taxa have been examined. The secretions of 13 glandular types have been analyzed chemically. The histology of 11 glands is known at the ultrastructural level, whereas that of 6 glands and 7 putative glandular structures is completely unknown. Comparative anatomical studies of the osmeterium, adenosma, and Verson's glands may yield useful information for phylogenetic reconstructions. Copyright © 2012 by Annual Reviews. All rights reserved.

  3. Acute effects of irradiation on exocrine pancreatic secretion in the pig

    International Nuclear Information System (INIS)

    Monti, P.; Scanff, P.; Joubert, C.; Vergnet, M.; Grison, S.

    1997-01-01

    Several reports on irradiation damages to the pancreas deal essentially with long-term morphologic changes but give few informations on pancreatic exocrine function. Therefore, the aim of the present work was to study the effects of a whole body gamma irradiation on the volume and enzyme activities of the pancreatic juice. The volume of pancreatic juice daily secreted decreased one day after irradiation (-40%, p < 0.01) and remained lower that the control value all over the experimental period (-65%, p < 0.01). Same response was observed for the total proteins secreted in the pancreatic juice but significant decrease was observed only the fourth and the fifth days after irradiation. Therefore, concentration of total protein secreted in the pancreatic juice was not altered all over the experimental period. Total activities of proteolytic enzymes, lipase and amylase led to decrease on day after irradiation and except for trypsin, the attenuated activity became significant from the third day after exposure. On the other hand, specific activities of the proteolytic enzymes and amylase did not show marked modifications after irradiation, whereas lipase specific activity was decreased. In conclusion, a whole body gamma irradiation resulted in a rapid and marked decrease of exocrine pancreatic secretion, in terms of volume as well as secreted enzymes. These modifications may, in part, contribute to the malabsorption of nutrients and these acute effects may be due to some modifications in the regulation of the exocrine pancreatic secretion

  4. Acute effects of irradiation on exocrine pancreatic secretion in the pig

    Energy Technology Data Exchange (ETDEWEB)

    Monti, P; Scanff, P; Joubert, C; Vergnet, M; Grison, S [CEA Fontenay-aux-Roses, 92 (France). Inst. de Protection et de Surete Nucleaire

    1997-03-01

    Several reports on irradiation damages to the pancreas deal essentially with long-term morphologic changes but give few informations on pancreatic exocrine function. Therefore, the aim of the present work was to study the effects of a whole body gamma irradiation on the volume and enzyme activities of the pancreatic juice. The volume of pancreatic juice daily secreted decreased one day after irradiation (-40%, p < 0.01) and remained lower that the control value all over the experimental period (-65%, p < 0.01). Same response was observed for the total proteins secreted in the pancreatic juice but significant decrease was observed only the fourth and the fifth days after irradiation. Therefore, concentration of total protein secreted in the pancreatic juice was not altered all over the experimental period. Total activities of proteolytic enzymes, lipase and amylase led to decrease on day after irradiation and except for trypsin, the attenuated activity became significant from the third day after exposure. On the other hand, specific activities of the proteolytic enzymes and amylase did not show marked modifications after irradiation, whereas lipase specific activity was decreased. In conclusion, a whole body gamma irradiation resulted in a rapid and marked decrease of exocrine pancreatic secretion, in terms of volume as well as secreted enzymes. These modifications may, in part, contribute to the malabsorption of nutrients and these acute effects may be due to some modifications in the regulation of the exocrine pancreatic secretion

  5. Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy.

    Science.gov (United States)

    Tran, T C K; van 't Hof, G; Kazemier, G; Hop, W C; Pek, C; van Toorenenbergen, A W; van Dekken, H; van Eijck, C H J

    2008-01-01

    Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Fifty-five patients who were treated for pancreatic and periampullary carcinoma and 19 patients with chronic pancreatitis were evaluated. Exocrine pancreatic function was evaluated by fecal elastase-1 test, while endocrine pancreatic function was assessed by plasma glucose level. The extent of fibrosis, duct dilation and endocrine tissue loss was examined histopathologically. A strong correlation was found between pancreatic fibrosis and elastase-1 level less than 100 microg/g (p pancreatic insufficiency. A strong correlation was found between pancreatic fibrosis and endocrine tissue loss (p pancreatic fibrosis nor endocrine tissue loss were correlated with the development of postoperative diabetes mellitus. Duct dilation alone was neither correlated with exocrine nor with endocrine function loss. The majority of patients develop severe exocrine pancreatic insufficiency after pancreatoduodenectomy. The extent of exocrine pancreatic insufficiency is strongly correlated with preoperative fibrosis. The loss of endocrine tissue does not correlate with postoperative diabetes mellitus. Preoperative dilation of the pancreatic duct per se does not predict exocrine or endocrine pancreatic insufficiency postoperatively. Copyright 2008 S. Karger AG, Basel.

  6. GDF15 regulates Kv2.1-mediated outward K+ current through the Akt/mTOR signalling pathway in rat cerebellar granule cells.

    Science.gov (United States)

    Wang, Chang-Ying; Huang, An-Qi; Zhou, Meng-Hua; Mei, Yan-Ai

    2014-05-15

    GDF15 (growth/differentiation factor 15), a novel member of the TGFβ (transforming growth factor β) superfamily, plays critical roles in the central and peripheral nervous systems, but the signal transduction pathways and receptor subtypes involved are not well understood. In the present paper, we report that GDF15 specifically increases the IK (delayed-rectifier outward K+ current) in rat CGNs (cerebellar granule neurons) in time- and concentration-dependent manners. The GDF15-induced amplification of the IK is mediated by the increased expression and reduced lysosome-dependent degradation of the Kv2.1 protein, the main α-subunit of the IK channel. Exposure of CGNs to GDF15 markedly induced the phosphorylation of ERK (extracellular-signal-regulated kinase), Akt and mTOR (mammalian target of rapamycin), but the GDF15-induced IK densities and increased expression of Kv2.1 were attenuated only by Akt and mTOR, and not ERK, inhibitors. Pharmacological inhibition of the Src-mediated phosphorylation of TGFβR2 (TGFβ receptor 2), not TGFβR1, abrogated the effect of GDF15 on IK amplification and Kv2.1 induction. Immunoprecipitation assays showed that GDF15 increased the tyrosine phosphorylation of TGFβRII in the CGN lysate. The results of the present study reveal a novel regulation of Kv2.1 by GDF15 mediated through the TGFβRII-activated Akt/mTOR pathway, which is a previously uncharacterized Smad-independent mechanism of GDF15 signalling.

  7. Interleukin-6 inhibits apoptosis of exocrine gland tissues under inflammatory conditions.

    Science.gov (United States)

    Zhou, Jing; Jin, Jun-O; Patel, Ekta S; Yu, Qing

    2015-12-01

    Interleukin (IL)-6 is a multi-functional cytokine that can either promote or suppress tissue inflammation depending on the specific disease context. IL-6 is elevated in the exocrine glands and serum of patients with Sjögren's syndrome (SS), but the specific role of IL-6 in the pathogenesis of this disease has not been defined. In this study, we showed that IL-6 expression levels were increased with age in C56BL/6.NOD-Aec1Aec2 mice, a primary SS model, and higher than the control C57BL/6 mice. To assess the role of IL-6 during the immunological phase of SS development, a neutralizing anti-IL-6 antibody was administered into 16 week-old female C56BL/6.NOD-Aec1Aec2 mice, 3 times weekly for a consecutive 8 weeks. Neutralization of endogenous IL-6 throughout the immunological phase of SS development led to increased apoptosis, caspase-3 activation, leukocytic infiltration, and IFN-γ- and TNF-α production in the salivary gland. To further determine the effect of IL-6 on the apoptosis of exocrine gland cells, recombinant human IL-6 or the neutralizing anti-IL-6 antibody was injected into female C57BL/6 mice that received concurrent injection of anti-CD3 antibody to induce the apoptosis of exocrine gland tissues. Neutralization of IL-6 enhanced, whereas administration of IL-6 inhibited apoptosis and caspase-3 activation in salivary and lacrimal glands in this model. The apoptosis-suppressing effect of IL-6 was associated with up-regulation of Bcl-xL and Mcl-1 in both glands. Moreover, IL-6 treatment induced activation of STAT3 and up-regulated Bcl-xL and Mcl-1 gene expression in a human salivary gland epithelial cell line. In conclusion, IL-6 inhibits the apoptosis of exocrine gland tissues and exerts a tissue-protective effect under inflammatory conditions including SS. These findings suggest the possibility of using this property of IL-6 to preserve exocrine gland tissue integrity and function under autoimmune and inflammatory conditions. Copyright © 2015 Elsevier

  8. Exocrine pancreatic insufficiency in diabetic patients: prevalence, mechanisms, and treatment.

    Science.gov (United States)

    Piciucchi, Matteo; Capurso, Gabriele; Archibugi, Livia; Delle Fave, Martina Maria; Capasso, Marina; Delle Fave, Gianfranco

    2015-01-01

    Pancreas is a doubled-entity organ, with both an exocrine and an endocrine component, reciprocally interacting in a composed system whose function is relevant for digestion, absorption, and homeostasis of nutrients. Thus, it is not surprising that disorders of the exocrine pancreas also affect the endocrine system and vice versa. It is well-known that patients with chronic pancreatitis develop a peculiar form of diabetes (type III), caused by destruction and fibrotic injury of islet cells. However, less is known on the influence of diabetes on pancreatic exocrine function. Pancreatic exocrine insufficiency (PEI) has been reported to be common in diabetics, with a prevalence widely ranging, in different studies, in both type I (25-74%) and type II (28-54%) diabetes. A long disease duration, high insulin requirement, and poor glycemic control seem to be risk factors for PEI occurrence. The impact of pancreatic exocrine replacement therapy on glycemic, insulin, and incretins profiles has not been fully elucidated. The present paper is aimed at reviewing published studies investigating the prevalence of PEI in diabetic patients and factors associated with its occurrence.

  9. Predictive factors for exocrine pancreatic insufficiency after pancreatoduodenectomy with pancreaticogastrostomy.

    Science.gov (United States)

    Nakamura, Hiroyuki; Murakami, Yoshiaki; Uemura, Kenichiro; Hayashidani, Yasuo; Sudo, Takeshi; Ohge, Hiroki; Sueda, Taijiro

    2009-07-01

    The aim of this study was to determine risk factors for exocrine pancreatic insufficiency after pancreatoduodenectomy (PD) with pancreaticogastrostomy (PG). A (13)C-labeled mixed triglyceride breath test was performed in 61 patients after PD to assess exocrine pancreatic function. Percent (13)CO(2) cumulative dose at 7 h pancreatic insufficiency. Abdominal computed tomography scans were utilized to assess the dilatation of the main pancreatic duct (MPD dilatation) in the remnant. Thirty-eight of 61 patients (62.3%) were diagnosed with exocrine pancreatic insufficiency. Univariate analysis identified significant associations between two preoperative factors (preoperative impaired endocrine function and a hard pancreatic texture induced by preexisting obstructive pancreatitis), plus one postoperative factor (MPD dilatation caused by PG stricture) and exocrine pancreatic insufficiency (P pancreatic insufficiency after PD may be partly explainable by preexisting obstructive pancreatitis prior to surgery, surgeons desiring to obtain better postoperative exocrine pancreatic function after PD would be well-advised to devote considerable attention to preventing PG stricture.

  10. Exocrine Pancreatic Insufficiency in Diabetic Patients: Prevalence, Mechanisms, and Treatment

    Directory of Open Access Journals (Sweden)

    Matteo Piciucchi

    2015-01-01

    Full Text Available Pancreas is a doubled-entity organ, with both an exocrine and an endocrine component, reciprocally interacting in a composed system whose function is relevant for digestion, absorption, and homeostasis of nutrients. Thus, it is not surprising that disorders of the exocrine pancreas also affect the endocrine system and vice versa. It is well-known that patients with chronic pancreatitis develop a peculiar form of diabetes (type III, caused by destruction and fibrotic injury of islet cells. However, less is known on the influence of diabetes on pancreatic exocrine function. Pancreatic exocrine insufficiency (PEI has been reported to be common in diabetics, with a prevalence widely ranging, in different studies, in both type I (25–74% and type II (28–54% diabetes. A long disease duration, high insulin requirement, and poor glycemic control seem to be risk factors for PEI occurrence. The impact of pancreatic exocrine replacement therapy on glycemic, insulin, and incretins profiles has not been fully elucidated. The present paper is aimed at reviewing published studies investigating the prevalence of PEI in diabetic patients and factors associated with its occurrence.

  11. Expression of the GABA(A) receptor alpha6 subunit in cultured cerebellar granule cells is developmentally regulated by activation of GABA(A) receptors

    DEFF Research Database (Denmark)

    Carlson, B X; Belhage, B; Hansen, Gert Helge

    1997-01-01

    Da (alpha6 subunit) radioactive peaks in sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In contrast, THIP-treated granule cells at 8 DIV demonstrated a small but significant decrease from control cultures in the photoincorporation of [3H]Ro15-4513 in the 51-kDa peak; however...... that the major effect of THIP was to increase alpha6 subunit clustering on granule cell bodies as well as neurites, 15-fold and sixfold, respectively. Using in situ hybridization, a small THIP-induced increase in alpha6 mRNA was detected at 4 DIV; however, no effect was apparent at 8 DIV. These data suggest...

  12. Kinetic test of pancreatic exocrine function

    International Nuclear Information System (INIS)

    Sawabu, Norio; Hirose, Shoichiro; Nakazima, Shin; Yoneda, Masao; Nishimura, Keigo

    1975-01-01

    In order to improve the diagnostic evaluation of pancreatic exocrine function, 75 Se-activity in the duodenal aspirate of twenty control subjects and 131 subjects with pancertic and/or gastrointestinal disease was measured following intravenous injection of 75 Se-selenomethionine. Radioactivity in the duodenal aspirate of the control subjects remained low until 80 min. It then rose rapidly and reached a plateau at 115 min. In contrast, radioactivity in the subjects with pancreatic diseases remained low, or rose only slowly throughout the period of collection. Radioactivity of the protein fraction (TCA-precipitable) in the 80 to 130 min. duodenal aspirates showed good separation between controls and subjects with pancreatic disease. The incidence of abnormalities of TCA-precipitable radioactivity in the 80 to 130 min. duodenal aspirates was significantly higher than that of the conventional PS-test parameters in groups with various pancreatic diseases. All of the subjects having an abnormal maximal ratio of TCA-precipitable radioactivity to protein (representing pancreatic enzyme synthesis) showed an abnormal distribution in output of TCA-precipitable radioactivity in 80 to 130 min. collection (representing both enzyme synthesis and excretion). On the other hand, subjects with an abnormal output of TCA-precipitable radioactivity in 80 to 130 min. could be separated into those with normal and abnormal ratios of TCA-precipitable radioactivity, suggesting the presence of two types of disturbance in pancreatic function. In the latter group both synthesis and secretion of enzyme were impaired. In the former group, secretion of enzyme was depressed, although enzyme synthesis was fairly well preserved. (author)

  13. Kinetic test of pancreatic exocrine function

    Energy Technology Data Exchange (ETDEWEB)

    Sawabu, N; Hirose, S; Nakazima, S; Yoneda, M; Nishimura, K [Kanazawa Univ. (Japan). School of Medicine

    1975-01-01

    In order to improve the diagnostic evaluation of pancreatic exocrine function, /sup 75/Se-activity in the duodenal aspirate of twenty control subjects and 131 subjects with pancertic and/or gastrointestinal disease was measured following intravenous injection of /sup 75/Se-selenomethionine. Radioactivity in the duodenal aspirate of the control subjects remained low until 80 min. It then rose rapidly and reached a plateau at 115 min. In contrast, radioactivity in the subjects with pancreatic diseases remained low, or rose only slowly throughout the period of collection. Radioactivity of the protein fraction (TCA-precipitable) in the 80 to 130 min. duodenal aspirates showed good separation between controls and subjects with pancreatic disease. The incidence of abnormalities of TCA-precipitable radioactivity in the 80 to 130 min. duodenal aspirates was significantly higher than that of the conventional PS-test parameters in groups with various pancreatic diseases. All of the subjects having an abnormal maximal ratio of TCA-precipitable radioactivity to protein (representing pancreatic enzyme synthesis) showed an abnormal distribution in output of TCA-precipitable radioactivity in 80 to 130 min. collection (representing both enzyme synthesis and excretion). On the other hand, subjects with an abnormal output of TCA-precipitable radioactivity in 80 to 130 min. could be separated into those with normal and abnormal ratios of TCA-precipitable radioactivity, suggesting the presence of two types of disturbance in pancreatic function. In the latter group both synthesis and secretion of enzyme were impaired. In the former group, secretion of enzyme was depressed, although enzyme synthesis was fairly well preserved.

  14. The life cycle of platelet granules [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Anish Sharda

    2018-02-01

    Full Text Available Platelet granules are unique among secretory vesicles in both their content and their life cycle. Platelets contain three major granule types—dense granules, α-granules, and lysosomes—although other granule types have been reported. Dense granules and α-granules are the most well-studied and the most physiologically important. Platelet granules are formed in large, multilobulated cells, termed megakaryocytes, prior to transport into platelets. The biogenesis of dense granules and α-granules involves common but also distinct pathways. Both are formed from the trans-Golgi network and early endosomes and mature in multivesicular bodies, but the formation of dense granules requires trafficking machinery different from that of α-granules. Following formation in the megakaryocyte body, both granule types are transported through and mature in long proplatelet extensions prior to the release of nascent platelets into the bloodstream. Granules remain stored in circulating platelets until platelet activation triggers the exocytosis of their contents. Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE proteins, located on both the granules and target membranes, provide the mechanical energy that enables membrane fusion during both granulogenesis and exocytosis. The function of these core fusion engines is controlled by SNARE regulators, which direct the site, timing, and extent to which these SNAREs interact and consequently the resulting membrane fusion. In this review, we assess new developments in the study of platelet granules, from their generation to their exocytosis.

  15. Mining the granule proteome

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Goetze, Jens P; Johnsen, Anders H

    2015-01-01

    Proteomics of secretory granules is an emerging strategy for identifying secreted proteins, including potentially novel candidate biomarkers and peptide hormones. In addition, proteomics can provide information about the abundance, localization and structure (post-translational modification) of g...

  16. Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy

    NARCIS (Netherlands)

    T.C. Tran; G. van 't Hof; G. Kazemier (Geert); W.C.J. Hop (Wim); C.J. Pek (Chulja); A.W. van Toorenenbergen (Albert); H. van Dekken (Herman); C.H.J. van Eijck (Casper)

    2008-01-01

    textabstractBackground: Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Methods: Fifty-five patients who were treated for pancreatic and

  17. Exocrine glands of Schwarziana quadripunctata (Hymenoptera, Apinae, Meliponini

    Directory of Open Access Journals (Sweden)

    C. CRUZ-LANDIM

    Full Text Available This article describes the location, anatomy, histology and ontogeny of adult Schwarziana quadripunctata exocrine glands. These glands appear either as individualized organs (salivary gland system and Dufour gland or as epidermis differentiation (tegumentary glands. Variations in the occurrence and degree of development among colony components with regard to their degree of maturity are also described.

  18. Jiang Tang Xiao Ke Granule Play an Anti-diabetic Role in Diabetic Mice Pancreatic Tissue by Regulating the mRNAs and MicroRNAs Associated with PI3K-Akt Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Fang-Fang Mo

    2017-11-01

    Full Text Available Purpose: To investigate the effect of JTXK granule on the expression pattern of miRNA in pancreatic tissue of KKAy diabetic mice, and to explore the molecular mechanism and pathways of JTXK granule in anti-diabetic effect.Methods: We used high fat diet (HFD to induce the KKAy diabetic mice and screened the differentially expressed miRNAs (DEMs between JTXK-treated group (n = 6 and the diabetic group (n = 6 using MicroRNA (miRNA Microarray. C57BL/6J mice were given a normal diet as the control group (n = 6. Subsequently, miRNA target gene prediction, GO and Pathway analysis were used to explore the function of DEMs. Finally, the mechanism of anti-diabetic effects of JTXK granule was tested by in vitro INS-1 pancreatic β-cell experiment.Results: The blood glucose and body weight of JTXK-treated group was significantly lower compared with the model group. Moreover, a total of 45 miRNAs with significant differences were detected in the model group and the JTXK-treated group (P ≤ 0.05, Fold Change > 2. Further, miRNA-mRNA analysis showed that the differential expression of mmu-miR-192-5p, mmu-miR-291a-3p, mmu-miR-320-3p, mmu-miR-139-5p and mmu-miR-378a-3p are closely related to pancreatic histological changes. In addition, pathway analysis showed that the DEMs were closely related to PI3K-Akt Signaling Pathway. Furthermore, the levels of serine/threonine-protein kinase (Akt, phosphorylated Akt (p-Akt and phosphorylated forkhead transcription factor O1 (p-Foxo1 in INS-1-FOXO1 overexpressing model cells were lower than those in normal group, while JTXK granules could increase the expression of Akt, p-Akt and p-Foxo1.Conclusions: The results showed that JTXK granule could play an anti-diabetic role by regulating the mRNA and miRNAs associated with PI3K-Akt pathway in diabetic mice pancreatic tissue.

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

    Energy Technology Data Exchange (ETDEWEB)

    Loo, Jr., Billy W. [Univ. of California, Berkeley, CA (United States)

    2000-06-01

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

  20. Roles of EDTA washing and Ca{sup 2+} regulation on the restoration of anammox granules inhibited by copper(II)

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Zheng-Zhe; Cheng, Ya-Fei; Zhou, Yu-Huang; Buayi, Xiemuguli [Department of Environmental Science and Engineering, Hangzhou Normal University, Hangzhou 310036 (China); Key Laboratory of Hangzhou City for Ecosystem Protection and Restoration, Hangzhou Normal University, Hangzhou 310036 (China); Jin, Ren-Cun, E-mail: jrczju@aliyun.com [Department of Environmental Science and Engineering, Hangzhou Normal University, Hangzhou 310036 (China); Key Laboratory of Hangzhou City for Ecosystem Protection and Restoration, Hangzhou Normal University, Hangzhou 310036 (China)

    2016-01-15

    Highlights: • 80.5% of the Cu in anammox granules was introduced via adsorption. • Cu(II) internalized on/into AnAOB cells plays a crucial role in toxicity. • EDTA washing contributes to the detoxification of anammox granules. • Ca{sup 2+} can stimulate the re-growth of damaged anammox consortium. - Abstract: We investigated the feasibility of using ethylene diamine tetraacetic acid (EDTA) washing followed by Ca{sup 2+} enhancement for the recovery of anammox reactors inhibited by Cu(II). Kinetic experiments and batch activity assays were employed to determine the optimal concentration of EDTA and washing time; and the performance and physiological dynamics were tracked by continuous-flow monitoring to evaluate the long-term effects. The two-step desorption process revealed that the Cu in anammox granules was primarily introduced via adsorption (approximately, 80.5%), and the portion of Cu in the dispersible layer was predominant (accounting for 71.1%). Afterwards, the Cu internalized in the cells (approximately, 14.7%) could diffuse out of the cells and be gradually washed out of the reactor over the next 20 days. The Ca{sup 2+} addition that followed led to an accelerated nitrogen removal rate recovery slope (0.1491 kgN m{sup −3} d{sup −2}) and a normal biomass growth rate (0.054 d{sup −1}). The nitrogen removal rate returned to normal levels within 90 days and gradual improvements in granular characteristics were also achieved. Therefore, this study provides a new insight that externally removing the adsorbed heavy metals followed by internally repairing the metabolic system may represent an optimal restoration strategy for anammox consortium damaged by heavy metals.

  1. Disintegration of aerobic granules induced by trans-2-decenoic acid.

    Science.gov (United States)

    Cai, Pei-Jie; Xiao, Xiang; He, Yan-Rong; Li, Wen-Wei; Yu, Lei; Yu, Han-Qing

    2013-01-01

    One current major hurdle to practical implementation of aerobic granule technology is the frequent occurrence of granule disintegration during long-term operation. However, the mechanism behind this is largely unclear today. Here, 2-decenoic acid, which has been previously demonstrated to be released by Pseudomonas aeruginosa and disperse biofilms, was found to also induce the disintegration of aerobic granules. A comparison of the solution compositions from samples of only trans-2-decenoic acid, only aerobic granules, and granules added with trans-2-decenoic acid shows that bacteria and extracellular polymeric substances (EPS) were stripped from granule surface upon trans-2-decenoic acid dosing. Due to the possible toxicity of trans-2-decenoic acid at a saturation concentration, the disintegrated granules and the milky suspension in the disintegration test showed a significantly lower oxygen uptake rate than the un-integrated granules. This work suggests that trans-2-decenoic acid released by microbes might play a critical role in regulating the disintegration of aerobic granules. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Rab3A, a possible marker of cortical granules, participates in cortical granule exocytosis in mouse eggs

    Energy Technology Data Exchange (ETDEWEB)

    Bello, Oscar Daniel; Cappa, Andrea Isabel; Paola, Matilde de; Zanetti, María Natalia [Instituto de Histología y Embriología, CONICET – Universidad Nacional de Cuyo, Av. Libertador 80, 5500 Mendoza (Argentina); Fukuda, Mitsunori [Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578 (Japan); Fissore, Rafael A. [Department of Veterinary and Animal Sciences, University of Massachusetts Amherst, 661 North Pleasant Street, Amherst, MA 01003 (United States); Mayorga, Luis S. [Instituto de Histología y Embriología, CONICET – Universidad Nacional de Cuyo, Av. Libertador 80, 5500 Mendoza (Argentina); Michaut, Marcela A., E-mail: mmichaut@gmail.com [Instituto de Histología y Embriología, CONICET – Universidad Nacional de Cuyo, Av. Libertador 80, 5500 Mendoza (Argentina); Facultad de Ciencias Exactas y Naturales, Universidad Nacional de Cuyo (Argentina)

    2016-09-10

    Fusion of cortical granules with the oocyte plasma membrane is the most significant event to prevent polyspermy. This particular exocytosis, also known as cortical reaction, is regulated by calcium and its molecular mechanism is still not known. Rab3A, a member of the small GTP-binding protein superfamily, has been implicated in calcium-dependent exocytosis and is not yet clear whether Rab3A participates in cortical granules exocytosis. Here, we examine the involvement of Rab3A in the physiology of cortical granules, particularly, in their distribution during oocyte maturation and activation, and their participation in membrane fusion during cortical granule exocytosis. Immunofluorescence and Western blot analysis showed that Rab3A and cortical granules have a similar migration pattern during oocyte maturation, and that Rab3A is no longer detected after cortical granule exocytosis. These results suggested that Rab3A might be a marker of cortical granules. Overexpression of EGFP-Rab3A colocalized with cortical granules with a Pearson correlation coefficient of +0.967, indicating that Rab3A and cortical granules have almost a perfect colocalization in the egg cortical region. Using a functional assay, we demonstrated that microinjection of recombinant, prenylated and active GST-Rab3A triggered cortical granule exocytosis, indicating that Rab3A has an active role in this secretory pathway. To confirm this active role, we inhibited the function of endogenous Rab3A by microinjecting a polyclonal antibody raised against Rab3A prior to parthenogenetic activation. Our results showed that Rab3A antibody microinjection abolished cortical granule exocytosis in parthenogenetically activated oocytes. Altogether, our findings confirm that Rab3A might function as a marker of cortical granules and participates in cortical granule exocytosis in mouse eggs. - Highlights: • Rab3A has a similar migration pattern to cortical granules in mouse oocytes. • Rab3A can be a marker of

  3. NEDDylation promotes stress granule assembly.

    Science.gov (United States)

    Jayabalan, Aravinth Kumar; Sanchez, Anthony; Park, Ra Young; Yoon, Sang Pil; Kang, Gum-Yong; Baek, Je-Hyun; Anderson, Paul; Kee, Younghoon; Ohn, Takbum

    2016-07-06

    Stress granules (SGs) harbour translationally stalled messenger ribonucleoproteins and play important roles in regulating gene expression and cell fate. Here we show that neddylation promotes SG assembly in response to arsenite-induced oxidative stress. Inhibition or depletion of key components of the neddylation machinery concomitantly inhibits stress-induced polysome disassembly and SG assembly. Affinity purification and subsequent mass-spectrometric analysis of Nedd8-conjugated proteins from translationally stalled ribosomal fractions identified ribosomal proteins, translation factors and RNA-binding proteins (RBPs), including SRSF3, a previously known SG regulator. We show that SRSF3 is selectively neddylated at Lys85 in response to arsenite. A non-neddylatable SRSF3 (K85R) mutant do not prevent arsenite-induced polysome disassembly, but fails to support the SG assembly, suggesting that the neddylation pathway plays an important role in SG assembly.

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

    Science.gov (United States)

    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

  5. Diabetes mellitus and exocrine pancreatic insufficiency (review of literature

    Directory of Open Access Journals (Sweden)

    L.T. Daminova

    2018-02-01

    Full Text Available Currently, an increasing importance is given to the study of the problem of exocrine pancreatic insufficiency, which is observed in a significant number of patients with diabetes mellitus (DM type 1 and 2 and can potentially affect the compensation of DM. The mechanism of reducing the external secretion of the pancreas in DM is associated with an imbalance of inhibitory and stimulating pancreatic secretion of hormones, with fibrosis of the gland as a result of diabetic angiopathy. In type 2 DM, the mechanisms that result from the metabolic syndrome are involved in the pathogenesis of exocrine pancreatic insufficiency. Enzyme replacement the­rapy should be considered as one of the promising methods of treating DM patients.

  6. Obstructed pancreaticojejunostomy partly explains exocrine insufficiency after pancreatic head resection.

    Science.gov (United States)

    Nordback, Isto; Parviainen, Mickael; Piironen, Anneli; Räty, Sari; Sand, Juhani

    2007-02-01

    The majority of patients with long-term survival after pancreatic head resection suffer from pancreatic exocrine insufficiency. The objective of this study was to investigate whether this is due to glandular malfunction or obstructed pancreaticojejunal anastomosis. Twenty-six patients (10 M, 16 F, mean age 61 years, range 34-81 years) were re-examined a median of 52 months (range 3-76 months) after pancreatic head resection and end-to-end invaginated pancreaticojejunostomy. Pancreatic exocrine function was measured by fecal elastase-1 assay. The size of the pancreatic remnant, glandular secretion and the flow through the anastomosis were analyzed with secretin-stimulated dynamic magnetic resonance pancreatography (D-MRP). All patients had pancreatic exocrine insufficiency, 24 (92%) of them having severe insufficiency. Eighteen patients (69%) reported moderate to severe diarrhea. Lowest fecal elastase-1 concentrations were associated with the initial diagnosis of chronic pancreatitis or ductal adenocarcinoma, suggesting preoperative primary or secondary chronic pancreatitis as important determinants. The size of the remnant gland did not correlate with the fecal elastase-1 concentrations. D-MRP failed in three patients. Severe glandular malfunctions were found in 7 (30%) of the 23 successful D-MRP examinations. The anastomosis was totally obstructed in 5 patients (22%) or partially obstructed in 6 (26%) but remained perfectly open in 5 patients (22%). The five patients with perfect anastomoses had the highest measured median fecal elastase-1 activity. Although late diarrhea and pancreatic exocrine insufficiency may be partly induced already by the disease treated with resection, at least half may be explained by obstructed anastomosis. To obtain better late functional results, improvements may be required in the surgical techniques.

  7. The cystic fibrosis of exocrine pancreas

    DEFF Research Database (Denmark)

    Wilschanski, Michael; Novak, Ivana

    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 acina...... (CF) and pancreatitis, and outline present and potential therapeutic approaches in CF treatment relevant to the pancreas....

  8. The biology and dynamics of mammalian cortical granules

    Directory of Open Access Journals (Sweden)

    Liu Min

    2011-11-01

    Full Text Available Abstract Cortical granules are membrane bound organelles located in the cortex of unfertilized oocytes. Following fertilization, cortical granules undergo exocytosis to release their contents into the perivitelline space. This secretory process, which is calcium dependent and SNARE protein-mediated pathway, is known as the cortical reaction. After exocytosis, the released cortical granule proteins are responsible for blocking polyspermy by modifying the oocytes' extracellular matrices, such as the zona pellucida in mammals. Mammalian cortical granules range in size from 0.2 um to 0.6 um in diameter and different from most other regulatory secretory organelles in that they are not renewed once released. These granules are only synthesized in female germ cells and transform an egg upon sperm entry; therefore, this unique cellular structure has inherent interest for our understanding of the biology of fertilization. Cortical granules are long thought to be static and awaiting in the cortex of unfertilized oocytes to be stimulated undergoing exocytosis upon gamete fusion. Not till recently, the dynamic nature of cortical granules is appreciated and understood. The latest studies of mammalian cortical granules document that this organelle is not only biochemically heterogeneous, but also displays complex distribution during oocyte development. Interestingly, some cortical granules undergo exocytosis prior to fertilization; and a number of granule components function beyond the time of fertilization in regulating embryonic cleavage and preimplantation development, demonstrating their functional significance in fertilization as well as early embryonic development. The following review will present studies that investigate the biology of cortical granules and will also discuss new findings that uncover the dynamic aspect of this organelle in mammals.

  9. Exocrine Gland Morphogenesis: Insights into the Role of Amphiregulin from Development to Disease.

    Science.gov (United States)

    Sisto, Margherita; Lorusso, Loredana; Ingravallo, Giuseppe; Lisi, Sabrina

    2017-12-01

    Amphiregulin (AREG) is a well-characterized member of the epidermal growth factor (EGF) family and is one of the ligands of the EGF receptor (EGFR). AREG plays a key role in mammalian development and in the control of branching morphogenesis in various organs. Furthermore, AREG participates in a wide range of physiological and pathological processes activating the major intracellular signalling cascades governing cell survival, proliferation and motility. In this article, we review current advances in exocrine glands morphogenesis, focusing on the salivary gland, and discuss the essential aspects of AREG structure, function and regulation, and its differential role within the EGFR family of ligands. Finally, we identify emerging aspects in AREG research applied to mammary gland development and the salivary gland autoimmune disease, Sjögren's syndrome.

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

    Science.gov (United States)

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

    2017-06-01

    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, 300:1104-1113, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  11. [Exocrine function of the pancreas in rats with experimental obesity].

    Science.gov (United States)

    Leshchenko, I V; Shevchuk, V H; Savcheniuk, O A; Falalieieva, T M; Sukhodolia, S A; Berehova, T V

    2014-01-01

    The influence of neonatal administration of hyperosmolar sodium chloride and sodium glutamate on the exocrine function of the pancreas in rats has been investigated. It was observed the development of acute pancreatitis under experimental obesity. The cross-section area of acini reduced by 12%, the cross-section area of acinocytes nuclei increased by 10%, the length between the lobes of the gland has grown by 48%. The level of amylase was increased by 43%, the levels of pancreatic amylase and lipase were increased by 68% and 24%, respectively.

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

    International Nuclear Information System (INIS)

    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 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 3 H-α-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 α-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

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

    Science.gov (United States)

    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.

  14. Liquid‐to‐solid ratio control as an advanced process control solution for continuous twin‐screw wet granulation

    DEFF Research Database (Denmark)

    Nicolaï, Niels; Leersnyder, Fien De; Copot, Dana

    2018-01-01

    for the dynamic behavior of the granule liquid‐to‐solid ratio (w) at the end of the granulation unit of a commercial ConsiGmaTM‐25 production line. Near‐infrared spectroscopy was used to monitor the granule composition in‐line. The outcome for both the tracking and regulator problem using either conventional...

  15. Collages of granulation pictures

    International Nuclear Information System (INIS)

    Dunn, R.B.; November, L.J.

    1985-01-01

    This paper describes two small-area selection schemes that the authors have applied to CCD observations of solar granulation. The first scheme, which the authors call the ''mosaic,'' divides the 128 x 128 array into 64 subarrays each containing 16 x 16 pixels. On each picture in the burst the RMS contrast of the fine structure is measured in each subarray and compared to the corresponding value in a table that contains the highest previous RMS values. The second scheme, which the authors call a ''collage,'' is similar except the RMS value is calculated smoothly within a sliding Gaussian window over the entire scene and the value of an individual pixel is gated into the final collage whenever the RMS contrast at that pixel location exceeds that of all previous frames taken during the burst

  16. Management of pancreatic exocrine insufficiency: Australasian Pancreatic Club recommendations.

    Science.gov (United States)

    Toouli, James; Biankin, Andrew V; Oliver, Mark R; Pearce, Callum B; Wilson, Jeremy S; Wray, Nicholas H

    2010-10-18

    Pancreatic exocrine insufficiency (PEI) occurs when the amounts of enzymes secreted into the duodenum in response to a meal are insufficient to maintain normal digestive processes. The main clinical consequence of PEI is fat maldigestion and malabsorption, resulting in steatorrhoea. Pancreatic exocrine function is commonly assessed by conducting a 3-day faecal fat test and by measuring levels of faecal elastase-1 and serum trypsinogen. Pancreatic enzyme replacement therapy is the mainstay of treatment for PEI. In adults, the initial recommended dose of pancreatic enzymes is 25,000 units of lipase per meal, titrating up to a maximum of 80,000 units of lipase per meal. In infants and children, the initial recommended dose of pancreatic enzymes is 500 units of lipase per gram of dietary fat; the maximum daily dose should not exceed 10,000 units of lipase per kilogram of bodyweight. Oral pancreatic enzymes should be taken with meals to ensure adequate mixing with the chyme. Adjunct therapy with acid-suppressing agents may be useful in patients who continue to experience symptoms of PEI despite high-dose enzyme therapy. A dietitian experienced in treating PEI should be involved in patient management. Dietary fat restriction is not recommended for patients with PEI. Patients with PEI should be encouraged to consume small, frequent meals and to abstain from alcohol. Medium-chain triglycerides do not provide any clear nutritional advantage over long-chain triglycerides, but can be trialled in patients who fail to gain or to maintain adequate bodyweight in order to increase energy intake.

  17. Identification of proteins involved in the pancreatic exocrine by exogenous ghrelin administration in Sprague-Dawley rats.

    Science.gov (United States)

    Lee, Kyung-Hoon; Wang, Tao; Jin, Yong-Cheng; Lee, Sang-Bum; Oh, Jin-Ju; Hwang, Jin-Hee; Lim, Ji-Na; Lee, Jae-Sung; Lee, Hong-Gu

    2014-01-01

    The aims of study were to investigate the effects of intraperitoneal (i.p.) infusion of ghrelin on pancreatic α-amylase outputs and the responses of pancreatic proteins to ghrelin that may relate to the pancreatic exocrine. Six male Sprague-Dawley rats (300 g) were randomly divided into two groups, a control group (C, n = 3) and a treatment group (T, 10.0μg/kg BW, n = 3). Blood samples were collected from rat caudal vein once time after one hour injection. The concentrations of plasma ghrelin, cholecystokinin (CCK) and alfa-amylase activity were evaluated by enzyme immunoassay (EIA) kit. Two-dimensional gel electrophoresis (2-DE) analysis was conducted to separate the proteins in pancreas tissue. Results showed that the i.p. infusion of ghrelin at doses of 10.0 μg/kg body weight (BW) increased the plasma ghrelin concentrations (p = 0.07) and elevated the plasma CCK level significantly (p amylase activity tended to increase. The proteomics analysis indicated that some pancreatic proteins with various functions were up- or down- regulated compared with control group. In conclusion, ghrelin may have role in the pancreatic exocrine, but the signaling pathway was still not clear. Therefore, much more functional studies focus on these found proteins are needed in the near future.

  18. Diabetes and exocrine pancreatic insufficiency in E2F1/E2F2 double-mutant mice.

    Science.gov (United States)

    Iglesias, Ainhoa; Murga, Matilde; Laresgoiti, Usua; Skoudy, Anouchka; Bernales, Irantzu; Fullaondo, Asier; Moreno, Bernardino; Lloreta, José; Field, Seth J; Real, Francisco X; Zubiaga, Ana M

    2004-05-01

    E2F transcription factors are thought to be key regulators of cell growth control. Here we use mutant mouse strains to investigate the function of E2F1 and E2F2 in vivo. E2F1/E2F2 compound-mutant mice develop nonautoimmune insulin-deficient diabetes and exocrine pancreatic dysfunction characterized by endocrine and exocrine cell dysplasia, a reduction in the number and size of acini and islets, and their replacement by ductal structures and adipose tissue. Mutant pancreatic cells exhibit increased rates of DNA replication but also of apoptosis, resulting in severe pancreatic atrophy. The expression of genes involved in DNA replication and cell cycle control was upregulated in the E2F1/E2F2 compound-mutant pancreas, suggesting that their expression is repressed by E2F1/E2F2 activities and that the inappropriate cell cycle found in the mutant pancreas is likely the result of the deregulated expression of these genes. Interestingly, the expression of ductal cell and adipocyte differentiation marker genes was also upregulated, whereas expression of pancreatic cell marker genes were downregulated. These results suggest that E2F1/E2F2 activity negatively controls growth of mature pancreatic cells and is necessary for the maintenance of differentiated pancreatic phenotypes in the adult.

  19. Cascade reactor: granule fabrication processes

    International Nuclear Information System (INIS)

    Erlandson, O.D.; Winkler, E.O.; Maya, I.; Pitts, J.H.

    1985-01-01

    A key feature of Cascade is the granular blanket. Of the many blanket material options open to Cascade, fabrication of Li 2 O granules was felt to offer the greatest challenge. The authors explored available methods for initial Li 2 O granule fabrication. They identified three cost-effective processes for fabricating Li 2 O granules: the VSM drop-melt furnace process, which is based on melting and spheroidizing irregularly shaped Li 2 O feed granules; the LiOH process, which spheroidizes liquefied LiOH and uses GA Technologies' sphere-forming procedures; and the Li 2 CO 3 sol-gel process, used for making spherical fuel particles for the high-temperature gas-cooled reactor (HTGR). Each process is described below

  20. Collages of granulation pictures

    Science.gov (United States)

    Dunn, R. B.; November, L. J.

    Two small-area selection schemes are applied to CCD observations of solar granulation. One procedure, referred to as mosaic, divides a 128 x 128 array into 64 subarrays of 16 x 16 pixels; the rms contrast of the fine structure is measured and compared in order to develop a mosaic of the subarrays. The second technique, collage, involves calculating rms values within a sliding Gaussian window and gating the pixel into the final image. Methods for assessing seeing quality, which involve the calculation of rms after high-pass filtering, are examined; a simple high-pass filter or an edge-locating function can be utilized for filtering. The rms map is then formed from the convolution of a Gaussian with either the high-pass or the Laplacian filters. The usefulness of the two procedures is demonstrated by applying the mosaic and collage processes to data recorded on July 17, 1983 with a CCD device on the NSO/Sac Peak Vacuum Tower Telescope.

  1. Proteins are secreted from heterogeneous prestored sources in the exocrine pancreas

    International Nuclear Information System (INIS)

    Miller, P.E.; Adelson, J.W.

    1987-01-01

    Recent studies demonstrating nonparallel regulated secretion of prestored digestive enzymes in tightly linked groups consistent with the exocytosis mechanisms led the authors to predict that digestive enzymes would be found to be secreted from heterogeneous sources within the exocrine pancreas. They explored whether the gland was heterogeneous with respect to its sources of prestored secretory proteins with a double isotopic label method not dependent on activity of secreted digestive enzymes. Rabbit pancreatic proteins were double labeled in vivo by injection of each animal with chemically identical but isotopically distinct mixtures of 3 H- and 14 C-labeled amino acids, which were administered separately or together on consecutive days after partial depletion of prestored proteins by administration of cholecystokinin (CCK), methacholine chloride, or saline in a protocol in which order of both isotope and secretagogue administration was varied. Three days after labeling, proteins were recovered by collection from cannulated pancreatic ducts of anesthetized animals after stimulation with alternating increasing doses of CCK and methacholine chloride. Correlation and regression analysis of isotopic outputs and variance analysis of specific radioactivities of secreted proteins showed sequestration into and secretion from heterogeneous pools of secretory proteins, directly confirming the hypothesis. These results provide a cell biological mechanism explaining regulated nonparallel secretion of digestive enzymes

  2. Is there adaptation of the exocrine pancreas in wild animal? The case of the Roe deer.

    Science.gov (United States)

    Guilloteau, Paul; Vitari, Francesca; Metzinger-Le Meuth, Valérie; Le Normand, Laurence; Romé, Véronique; Savary, Gérard; Delaby, Luc; Domeneghini, Cinzia; Morisset, Jean

    2012-05-28

    Physiology of the exocrine pancreas has been well studied in domestic and in laboratory animals as well as in humans. However, it remains quite unknown in wildlife mammals. Roe deer and cattle (including calf) belong to different families but have a common ancestor. This work aimed to evaluate in the Roe deer, the adaptation to diet of the exocrine pancreatic functions and regulations related to animal evolution and domestication. Forty bovine were distributed into 2 groups of animals either fed exclusively with a milk formula (monogastric) or fed a dry feed which allowed for rumen function to develop, they were slaughtered at 150 days of age. The 35 Roe deer were wild animals living in the temperate broadleaf and mixed forests, shot during the hunting season and classified in two groups adult and young. Immediately after death, the pancreas was removed for tissue sample collection and then analyzed. When expressed in relation to body weight, pancreas, pancreatic protein weights and enzyme activities measured were higher in Roe deer than in calf. The 1st original feature is that in Roe deer, the very high content in pancreatic enzymes seems to be related to specific digestive products observed (proline-rich proteins largely secreted in saliva) which bind tannins, reducing their deleterious effects on protein digestion. The high chymotrypsin and elastase II quantities could allow recycling of proline-rich proteins. In contrast, domestication and rearing cattle resulted in simplified diet with well digestible components. The 2nd feature is that in wild animal, both receptor subtypes of the CCK/gastrin family peptides were present in the pancreas as in calf, although CCK-2 receptor subtype was previously identified in higher mammals. Bovine species could have lost some digestive capabilities (no ingestion of great amounts of tannin-rich plants, capabilities to secrete high amounts of proline-rich proteins) compared with Roe deer species. CCK and gastrin could play

  3. Is there adaptation of the exocrine pancreas in wild animal? The case of the Roe Deer

    Directory of Open Access Journals (Sweden)

    Guilloteau Paul

    2012-05-01

    Full Text Available Abstract Background Physiology of the exocrine pancreas has been well studied in domestic and in laboratory animals as well as in humans. However, it remains quite unknown in wildlife mammals. Roe deer and cattle (including calf belong to different families but have a common ancestor. This work aimed to evaluate in the Roe deer, the adaptation to diet of the exocrine pancreatic functions and regulations related to animal evolution and domestication. Results Forty bovine were distributed into 2 groups of animals either fed exclusively with a milk formula (monogastric or fed a dry feed which allowed for rumen function to develop, they were slaughtered at 150 days of age. The 35 Roe deer were wild animals living in the temperate broadleaf and mixed forests, shot during the hunting season and classified in two groups adult and young. Immediately after death, the pancreas was removed for tissue sample collection and then analyzed. When expressed in relation to body weight, pancreas, pancreatic protein weights and enzyme activities measured were higher in Roe deer than in calf. The 1st original feature is that in Roe deer, the very high content in pancreatic enzymes seems to be related to specific digestive products observed (proline-rich proteins largely secreted in saliva which bind tannins, reducing their deleterious effects on protein digestion. The high chymotrypsin and elastase II quantities could allow recycling of proline-rich proteins. In contrast, domestication and rearing cattle resulted in simplified diet with well digestible components. The 2nd feature is that in wild animal, both receptor subtypes of the CCK/gastrin family peptides were present in the pancreas as in calf, although CCK-2 receptor subtype was previously identified in higher mammals. Conclusions Bovine species could have lost some digestive capabilities (no ingestion of great amounts of tannin-rich plants, capabilities to secrete high amounts of proline-rich proteins

  4. The Relation Between Malnutrition and the Exocrine Pancreas: A Systematic Review

    NARCIS (Netherlands)

    Bartels, Rosalie H.; van den Brink, Deborah A.; Bandsma, Robert H.; Boele van Hensbroek, Michael; Tabbers, Merit M.; Voskuijl, Wieger P.

    2018-01-01

    Objective: The relation between malnutrition and exocrine pancreatic insufficiency (EPI) has been described previously, but it is unclear if malnutrition leads to EPI or vice versa. We systematically synthesized current evidence evaluating the association between malnutrition and EPI in children.

  5. [Roles of protease-activated receptor-2 (PAR-2), a G protein-coupled receptor, in modulation of exocrine gland functions].

    Science.gov (United States)

    Nishikawa, Hiroyuki

    2006-07-01

    Protease-activated receptor-2 (PAR-2), a G protein-coupled receptor, is activated by proteolytic unmasking of the N-terminal extracellular tethered ligand that presumably binds to the extracellular loop 2 of the receptor itself. PAR-2 is widely distributed in the mammalian body and plays various roles in biological events in the cardiovascular, respiratory, alimentary, and central neurons systems. PAR-2-activating peptides administered systemically to mice and rats trigger prompt salivation in vivo. In an in vitro study, PAR-2 agonists including the endogenous PAR-2 activator trypsin induce secretion of amylase and mucin from isolated rat parotid glands and sublingual glands, respectively. PAR-2-activating peptides administered systemically also modulate pancreatic exocrine secretion in vivo as well as in vitro. In the gastric mucosa, PAR-2 stimulation enhances secretion of mucus and pepsinogen and suppresses acid secretion. Tear secretion can also be caused by PAR-2-related peptides in PAR-2-dependent and -independent manners. PAR-2 thus plays a general or key role in the regulation of exocrine secretion. This review focuses on the physiologic and/or pathophysiologic roles of PAR-2 in glandular exocrine secretion. The possibility of PAR-2 as a target for drug development is also discussed.

  6. Inducible tertiary lymphoid structures, autoimmunity and exocrine dysfunction in a novel model of salivary gland inflammation in C57BL/6 mice§

    Science.gov (United States)

    Bombardieri, Michele; Barone, Francesca; Lucchesi, Davide; Nayar, Saba; van den Berg, Wim B; Proctor, Gordon; Buckley, Christopher D; Pitzalis, Costantino

    2012-01-01

    Salivary glands in patients with Sjögren’s syndrome (SS) develop ectopic lymphoid structures (ELS) characterized by B/T cell compartmentalization, the formation of high endothelial venules (HEV), follicular dendritic cell networks (FDCs), functional B cell activation with expression of activation-induced cytidine deaminase (AID) as well as local differentiation of autoreactive plasma cells. The mechanisms triggering ELS formation, autoimmunity and exocrine dysfunction in SS are largely unknown. Here we present a novel model of inducible ectopic lymphoid tissue formation, breach of humoral self-tolerance and salivary hypofunction following delivery of a replication-deficient adenovirus-5 (AdV5) in submandibular glands of C57BL/6 mice through retrograde excretory duct cannulation. In this model, inflammation rapidly and consistently evolves from diffuse infiltration towards the development of SS-like periductal lymphoid aggregates within 2 weeks from AdV delivery. These infiltrates progressively acquire ELS features and support functional GL7+/AID+ germinal centers. Formation of ELS is preceded by ectopic expression of lymphoid chemokines CXCL13, CCL19 and lymphotoxin-β and is associated with development of anti-nuclear antibodies in up to 75% of mice. Finally, reduction in salivary flow was observed over 3 weeks post AdV infection consistent with exocrine gland dysfunction as a consequence of the inflammatory response. This novel model has the potential to unravel the cellular and molecular mechanisms regulating ELS formation and their role in exocrine dysfunction and autoimmunity in SS. PMID:22942425

  7. Inducible tertiary lymphoid structures, autoimmunity, and exocrine dysfunction in a novel model of salivary gland inflammation in C57BL/6 mice.

    Science.gov (United States)

    Bombardieri, Michele; Barone, Francesca; Lucchesi, Davide; Nayar, Saba; van den Berg, Wim B; Proctor, Gordon; Buckley, Christopher D; Pitzalis, Costantino

    2012-10-01

    Salivary glands in patients with Sjögren's syndrome (SS) develop ectopic lymphoid structures (ELS) characterized by B/T cell compartmentalization, the formation of high endothelial venules, follicular dendritic cell networks, functional B cell activation with expression of activation-induced cytidine deaminase, as well as local differentiation of autoreactive plasma cells. The mechanisms that trigger ELS formation, autoimmunity, and exocrine dysfunction in SS are largely unknown. In this article, we present a novel model of inducible ectopic lymphoid tissue formation, breach of humoral self-tolerance, and salivary hypofunction after delivery of a replication-deficient adenovirus-5 in submandibular glands of C57BL/6 mice through retrograde excretory duct cannulation. In this model, inflammation rapidly and consistently evolves from diffuse infiltration toward the development of SS-like periductal lymphoid aggregates within 2 wk from AdV delivery. These infiltrates progressively acquire ELS features and support functional GL7(+)/activation-induced cytidine deaminase(+) germinal centers. Formation of ELS is preceded by ectopic expression of lymphoid chemokines CXCL13, CCL19, and lymphotoxin-β, and is associated with development of anti-nuclear Abs in up to 75% of mice. Finally, reduction in salivary flow was observed over 3 wk post-AdV infection, consistent with exocrine gland dysfunction as a consequence of the inflammatory response. This novel model has the potential to unravel the cellular and molecular mechanisms that regulate ELS formation and their role in exocrine dysfunction and autoimmunity in SS.

  8. Rice starch granule amylolysis--differentiating effects of particle size, morphology, thermal properties and crystalline polymorph.

    Science.gov (United States)

    Dhital, Sushil; Butardo, Vito M; Jobling, Stephen A; Gidley, Michael J

    2015-01-22

    The underlying mechanism of amylolysis of rice starch granules was investigated using isolated starch granules from wild-type, as well as SBEIIb mutant and down-regulated lines. Fused granule agglomerates isolated from mutant and transgenic lines were hydrolysed at similar rates by amylases, and had similar crystalline patterns and thermal properties as individual granules. Surface pores, a feature previously only reported for A-polymorphic starch granules, were also observed in B- and C-polymorphic rice starch granules. Although the microscopic patterns of hydrolysis among granules with different crystalline polymorphs were qualitatively similar, the extent and the rate of amylolysis were different, suggesting that B-type crystalline polymorphs are intrinsically more resistant to enzymatic hydrolysis than A-type in rice starch granules. It is proposed that the slightly longer branch lengths of amylopectin which leads to the formation of more stable B-type double helical structures compared to their A-type counterparts is the major parameter, with other factors such as granule size, surface pores and interior channels having secondary roles, in determining the rate of enzymatic hydrolysis of rice starch granules. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Abnormal ion content, hydration and granule expansion of the secretory granules from cystic fibrosis airway glandular cells

    International Nuclear Information System (INIS)

    Baconnais, S.; Delavoie, F.; Zahm, J.M.; Milliot, M.; Terryn, C.; Castillon, N.; Banchet, V.; Michel, J.; Danos, O.; Merten, M.; Chinet, T.; Zierold, K.; Bonnet, N.; Puchelle, E.; Balossier, G.

    2005-01-01

    The absence or decreased expression of cystic fibrosis transmembrane conductance regulator (CFTR) induces increased Na + absorption and hyperabsorption of the airway surface liquid (ASL) resulting in a dehydrated and hyperviscous ASL. Although the implication of abnormal airway submucosal gland function has been suggested, the ion and water content in the Cystic Fibrosis (CF) glandular secretory granules, before exocytosis, is unknown. We analyzed, in non-CF and CF human airway glandular cell lines (MM-39 and KM4, respectively), the ion content in the secretory granules by electron probe X-ray microanalysis and the water content by quantitative dark field imaging on freeze-dried cryosections. We demonstrated that the ion content (Na + , Mg 2+ , P, S and Cl - ) is significantly higher and the water content significantly lower in secretory granules from the CF cell line compared to the non-CF cell line. Using videomicroscopy, we observed that the secretory granule expansion was deficient in CF glandular cells. Transfection of CF cells with CFTR cDNA or inhibition of non-CF cells with CFTR inh -172, respectively restored or decreased the water content and granule expansion, in parallel with changes in ion content. We hypothesize that the decreased water and increased ion content in glandular secretory granules may contribute to the dehydration and increased viscosity of the ASL in CF

  10. Pancreatic endocrine and exocrine function in children following near-total pancreatectomy for diffuse congenital hyperinsulinism.

    Science.gov (United States)

    Arya, Ved Bhushan; Senniappan, Senthil; Demirbilek, Huseyin; Alam, Syeda; Flanagan, Sarah E; Ellard, Sian; Hussain, Khalid

    2014-01-01

    Congenital hyperinsulinism (CHI), the commonest cause of persistent hypoglycaemia, has two main histological subtypes: diffuse and focal. Diffuse CHI, if medically unresponsive, is managed with near-total pancreatectomy. Post-pancreatectomy, in addition to persistent hypoglycaemia, there is a very high risk of diabetes mellitus and pancreatic exocrine insufficiency. International referral centre for the management of CHI. Medically unresponsive diffuse CHI patients managed with near-total pancreatectomy between 1994 and 2012. Near-total pancreatectomy. Persistent hypoglycaemia post near-total pancreatectomy, insulin-dependent diabetes mellitus, clinical and biochemical (faecal elastase 1) pancreatic exocrine insufficiency. Of more than 300 patients with CHI managed during this time period, 45 children had medically unresponsive diffuse disease and were managed with near-total pancreatectomy. After near-total pancreatectomy, 60% of children had persistent hypoglycaemia requiring medical interventions. The incidence of insulin dependent diabetes mellitus was 96% at 11 years after surgery. Thirty-two patients (72%) had biochemical evidence of severe pancreatic exocrine insufficiency (Faecal elastase 1insufficiency was observed in 22 (49%) patients. No statistically significant difference in weight and height standard deviation score (SDS) was found between untreated subclinical pancreatic exocrine insufficiency patients and treated clinical pancreatic exocrine insufficiency patients. The outcome of diffuse CHI patients after near-total pancreatectomy is very unsatisfactory. The incidence of persistent hypoglycaemia and insulin-dependent diabetes mellitus is very high. The presence of clinical rather than biochemical pancreatic exocrine insufficiency should inform decisions about pancreatic enzyme supplementation.

  11. Thirty-day outcomes underestimate endocrine and exocrine insufficiency after pancreatic resection.

    Science.gov (United States)

    Lim, Pei-Wen; Dinh, Kate H; Sullivan, Mary; Wassef, Wahid Y; Zivny, Jaroslav; Whalen, Giles F; LaFemina, Jennifer

    2016-04-01

    Long-term incidence of endocrine and exocrine insufficiency after pancreatectomy is poorly described. We analyze the long-term risks of pancreatic insufficiency after pancreatectomy. Subjects who underwent pancreatectomy from 2002 to 2012 were identified from a prospective database (n = 227). Subjects who underwent total pancreatectomy or pancreatitis surgery were excluded. New post-operative endocrine and exocrine insufficiency was defined as the need for new pharmacologic intervention within 1000 days from resection. 28 (16%) of 178 subjects without pre-existing endocrine insufficiency developed post-operative endocrine insufficiency: 7 (25%) did so within 30 days, 8 (29%) between 30 and 90 days, and 13 (46%) after 90 days. 94 (43%) of 214 subjects without pre-operative exocrine insufficiency developed exocrine insufficiency: 20 (21%) did so within 30 days, 29 (31%) between 30 and 90 days, and 45 (48%) after 90 days. Adjuvant radiation was associated with new endocrine insufficiency. On multivariate regression, pancreaticoduodenectomy and chemotherapy were associated with a greater risk of exocrine insufficiency. Reporting 30-day functional outcomes for pancreatic resection is insufficient, as nearly 45% of subjects who develop disease do so after 90 days. Reporting of at least 90-day outcomes may more reliably assess risk for post-operative endocrine and exocrine insufficiency. Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  12. Plant RNA Regulatory Network and RNA Granules in Virus Infection

    Directory of Open Access Journals (Sweden)

    Kristiina Mäkinen

    2017-12-01

    Full Text Available Regulation of post-transcriptional gene expression on mRNA level in eukaryotic cells includes translocation, translation, translational repression, storage, mRNA decay, RNA silencing, and nonsense-mediated decay. These processes are associated with various RNA-binding proteins and cytoplasmic ribonucleoprotein complexes many of which are conserved across eukaryotes. Microscopically visible aggregations formed by ribonucleoprotein complexes are termed RNA granules. Stress granules where the translationally inactive mRNAs are stored and processing bodies where mRNA decay may occur present the most studied RNA granule types. Diverse RNP-granules are increasingly being assigned important roles in viral infections. Although the majority of the molecular level studies on the role of RNA granules in viral translation and replication have been conducted in mammalian systems, some studies link also plant virus infection to RNA granules. An increasing body of evidence indicates that plant viruses require components of stress granules and processing bodies for their replication and translation, but how extensively the cellular mRNA regulatory network is utilized by plant viruses has remained largely enigmatic. Antiviral RNA silencing, which is an important regulator of viral RNA stability and expression in plants, is commonly counteracted by viral suppressors of RNA silencing. Some of the RNA silencing suppressors localize to cellular RNA granules and have been proposed to carry out their suppression functions there. Moreover, plant nucleotide-binding leucine-rich repeat protein-mediated virus resistance has been linked to enhanced processing body formation and translational repression of viral RNA. Many interesting questions relate to how the pathways of antiviral RNA silencing leading to viral RNA degradation and/or repression of translation, suppression of RNA silencing and viral RNA translation converge in plants and how different RNA granules and

  13. Plant RNA Regulatory Network and RNA Granules in Virus Infection.

    Science.gov (United States)

    Mäkinen, Kristiina; Lõhmus, Andres; Pollari, Maija

    2017-01-01

    Regulation of post-transcriptional gene expression on mRNA level in eukaryotic cells includes translocation, translation, translational repression, storage, mRNA decay, RNA silencing, and nonsense-mediated decay. These processes are associated with various RNA-binding proteins and cytoplasmic ribonucleoprotein complexes many of which are conserved across eukaryotes. Microscopically visible aggregations formed by ribonucleoprotein complexes are termed RNA granules. Stress granules where the translationally inactive mRNAs are stored and processing bodies where mRNA decay may occur present the most studied RNA granule types. Diverse RNP-granules are increasingly being assigned important roles in viral infections. Although the majority of the molecular level studies on the role of RNA granules in viral translation and replication have been conducted in mammalian systems, some studies link also plant virus infection to RNA granules. An increasing body of evidence indicates that plant viruses require components of stress granules and processing bodies for their replication and translation, but how extensively the cellular mRNA regulatory network is utilized by plant viruses has remained largely enigmatic. Antiviral RNA silencing, which is an important regulator of viral RNA stability and expression in plants, is commonly counteracted by viral suppressors of RNA silencing. Some of the RNA silencing suppressors localize to cellular RNA granules and have been proposed to carry out their suppression functions there. Moreover, plant nucleotide-binding leucine-rich repeat protein-mediated virus resistance has been linked to enhanced processing body formation and translational repression of viral RNA. Many interesting questions relate to how the pathways of antiviral RNA silencing leading to viral RNA degradation and/or repression of translation, suppression of RNA silencing and viral RNA translation converge in plants and how different RNA granules and their individual

  14. Effect of P2X(7) receptor knockout on exocrine secretion of pancreas, salivary glands and lacrimal glands.

    Science.gov (United States)

    Novak, Ivana; Jans, Ida M; Wohlfahrt, Louise

    2010-09-15

    The purinergic P2X(7) receptors are expressed in different cell types where they have varied functions, including regulation of cell survival. The P2X(7) receptors are also expressed in exocrine glands, but their integrated role in secretion is unclear. The aim of our study was to determine whether the P2X(7) receptors affect fluid secretion in pancreas, salivary glands and tear glands. We monitored gland secretions in in vivo preparations of wild-type and P2X(7)(-/-) (Pfizer) mice stimulated with pilocarpine. In cell preparations from pancreas, parotid and lacrimal glands we measured ATP release and intracellular Ca(2+) activity using Fura-2. The data showed that pancreatic secretion and salivary secretions were reduced in P2X(7)(-/-) mice, and in contrast, tear secretion was increased in P2X(7)(-/-) mice. The secretory phenotype was also dependent on the sex of the animal, such that males were more dependent on the P2X(7) receptor expression. ATP release in all cell preparations could be elicited by carbachol and other agonists, and this was independent of the P2X(7) receptor expression. ATP and carbachol increased intracellular Ca(2+) activity, but responses depended on the gland type, presence of the P2X(7) receptor and the sex of the animal. Together, these results demonstrate that cholinergic stimulation leads to release of ATP that can via P2X(7) receptors up-regulate pancreatic and salivary secretion but down-regulate tear secretion. Our data also indicate that there is an interaction between purinergic and cholinergic receptor signalling and that function of the P2X(7) receptor is suppressed in females. We conclude that the P2X(7) receptors are important in short-term physiological regulation of exocrine gland secretion.

  15. Effect of P2X7 receptor knockout on exocrine secretion of pancreas, salivary glands and lacrimal glands

    Science.gov (United States)

    Novak, Ivana; Jans, Ida M; Wohlfahrt, Louise

    2010-01-01

    The purinergic P2X7 receptors are expressed in different cell types where they have varied functions, including regulation of cell survival. The P2X7 receptors are also expressed in exocrine glands, but their integrated role in secretion is unclear. The aim of our study was to determine whether the P2X7 receptors affect fluid secretion in pancreas, salivary glands and tear glands. We monitored gland secretions in in vivo preparations of wild-type and P2X7−/− (Pfizer) mice stimulated with pilocarpine. In cell preparations from pancreas, parotid and lacrimal glands we measured ATP release and intracellular Ca2+ activity using Fura-2. The data showed that pancreatic secretion and salivary secretions were reduced in P2X7−/− mice, and in contrast, tear secretion was increased in P2X7−/− mice. The secretory phenotype was also dependent on the sex of the animal, such that males were more dependent on the P2X7 receptor expression. ATP release in all cell preparations could be elicited by carbachol and other agonists, and this was independent of the P2X7 receptor expression. ATP and carbachol increased intracellular Ca2+ activity, but responses depended on the gland type, presence of the P2X7 receptor and the sex of the animal. Together, these results demonstrate that cholinergic stimulation leads to release of ATP that can via P2X7 receptors up-regulate pancreatic and salivary secretion but down-regulate tear secretion. Our data also indicate that there is an interaction between purinergic and cholinergic receptor signalling and that function of the P2X7 receptor is suppressed in females. We conclude that the P2X7 receptors are important in short-term physiological regulation of exocrine gland secretion. PMID:20643770

  16. Platelet granule exocytosis: A comparison with chromaffin cells

    Directory of Open Access Journals (Sweden)

    Jennifer eFitch-Tewfik

    2013-06-01

    Full Text Available The rapid secretion of bioactive amines from chromaffin cells constitutes an important component of the fight or flight response of mammals to stress. Platelets respond to stresses within the vasculature by rapidly secreting cargo at sites of injury, inflammation, or infection. Although chromaffin cells derive from the neural crest and platelets from bone marrow megakaryocytes, both have evolved a heterogeneous assemblage of granule types and a mechanism for efficient release. This article will provide an overview of granule formation and exocytosis in platelets with an emphasis on areas in which the study of chromaffin cells has influenced that of platelets and on similarities between the two secretory systems. Commonalities include the use of transporters to concentrate bioactive amines and other cargos into granules, the role of cytoskeletal remodeling in granule exocytosis, and the use of granules to provide membrane for cytoplasmic projections. The SNAREs and SNARE accessory proteins used by each cell type will also be considered. Finally, we will discuss the newly appreciated role of dynamin family proteins in regulated fusion pore formation. This evaluation of the comparative cell biology of regulated exocytosis in platelets and chromaffin cells demonstrates a convergence of mechanisms between two disparate cell types both tasked with responding rapidly to physiological stimuli.

  17. [Relation between gene mutations and pancreatic exocrine function in patients with cystic fibrosis].

    Science.gov (United States)

    Radivojević, D; Guć-Sćekić, M; Djurisić, M; Lalić, T; Minić, P; Kanavakis, E

    2001-01-01

    Cystic fibrosis (CF), is the most common autosomal-recessive disease in Caucasians, with an incidence of approximately 1:2500 live births and a carrier frequency of approximately 4-5%. Causes of the disease are mutations in the CF gene which is located on chromosome 7 (region 7q31). Although a single mutation, a deletion of phenylalanine at position 508 (DF508) in exon 10, accounts for almost 70% of all CF chromosomes, over 900 other mutations have been identified in this large gene. CF gene encodes a membrane protein, which functions as aion channel- CFTR (cystic fibrosis transmembrane regulator protein). The exocrine pancreas is a gland that secretes water, enzymes and electrolytes into the intestinal lumen. These enzymes are needed for the normal digestion of food, and their reduced secretion in cystic fibrosis will cause malabsortion and malnutrition in CF patients. Pancreatic dysfunction in CF begins in uteri. Most patients with CF typically present insufficient pancreatic exocrine function (PI phenotype) and 10-15% of CF patients are pancreatic sufficient (PS phenotype). It has been shown elsewhere that the pancreatic function status in CF could be correlated to mutations in the CFTR gene. To determine the relation between genotype and pancreatic status, we analyzed 32 CF patients in whom both CF gene mutant alleles were identified (Table 1). Patients included in this study attended the Paediatric Department of Mother and Child Health Institute in Belgrade. The diagnosis was based on typical clinical manifestations and high levels of sweat chloride concentration (higher than 60 mmol/L). Of the 32 patients studied, only one (3.12%) was PS and the rest (96.88%) had PI phenotype. For each CF genotype the number of patients who were PI or PS is given in Table 1. The most striking observation was that all given genotypes correlated with either PI or PS, but not with both. On the basis of both preceding hypotheses and our present data (Table 2 and Table 3), it was

  18. Mouse Pancreas Tissue Slice Culture Facilitates Long-Term Studies of Exocrine and Endocrine Cell Physiology in situ

    OpenAIRE

    Marciniak, Anja; Selck, Claudia; Friedrich, Betty; Speier, Stephan

    2013-01-01

    Studies on pancreatic cell physiology rely on the investigation of exocrine and endocrine cells in vitro. Particularly, in the case of the exocrine tissue these studies have suffered from a reduced functional viability of acinar cells in culture. As a result not only investigations on dispersed acinar cells and isolated acini were limited in their potential, but also prolonged studies on pancreatic exocrine and endocrine cells in an intact pancreatic tissue environment were unfeasible. To ove...

  19. Pancreatic endocrine and exocrine function in children following near-total pancreatectomy for diffuse congenital hyperinsulinism.

    Directory of Open Access Journals (Sweden)

    Ved Bhushan Arya

    Full Text Available Congenital hyperinsulinism (CHI, the commonest cause of persistent hypoglycaemia, has two main histological subtypes: diffuse and focal. Diffuse CHI, if medically unresponsive, is managed with near-total pancreatectomy. Post-pancreatectomy, in addition to persistent hypoglycaemia, there is a very high risk of diabetes mellitus and pancreatic exocrine insufficiency.International referral centre for the management of CHI.Medically unresponsive diffuse CHI patients managed with near-total pancreatectomy between 1994 and 2012.Near-total pancreatectomy.Persistent hypoglycaemia post near-total pancreatectomy, insulin-dependent diabetes mellitus, clinical and biochemical (faecal elastase 1 pancreatic exocrine insufficiency.Of more than 300 patients with CHI managed during this time period, 45 children had medically unresponsive diffuse disease and were managed with near-total pancreatectomy. After near-total pancreatectomy, 60% of children had persistent hypoglycaemia requiring medical interventions. The incidence of insulin dependent diabetes mellitus was 96% at 11 years after surgery. Thirty-two patients (72% had biochemical evidence of severe pancreatic exocrine insufficiency (Faecal elastase 1<100 µg/g. Clinical exocrine insufficiency was observed in 22 (49% patients. No statistically significant difference in weight and height standard deviation score (SDS was found between untreated subclinical pancreatic exocrine insufficiency patients and treated clinical pancreatic exocrine insufficiency patients.The outcome of diffuse CHI patients after near-total pancreatectomy is very unsatisfactory. The incidence of persistent hypoglycaemia and insulin-dependent diabetes mellitus is very high. The presence of clinical rather than biochemical pancreatic exocrine insufficiency should inform decisions about pancreatic enzyme supplementation.

  20. The forced swimming-induced behavioural immobility response involves histone H3 phospho-acetylation and c-Fos induction in dentate gyrus granule neurons via activation of the N-methyl-D-aspartate/extracellular signal-regulated kinase/mitogen- and stress-activated kinase signalling pathway.

    Science.gov (United States)

    Chandramohan, Yalini; Droste, Susanne K; Arthur, J Simon C; Reul, Johannes M H M

    2008-05-01

    The hippocampus is involved in learning and memory. Previously, we have shown that the acquisition of the behavioural immobility response after a forced swim experience is associated with chromatin modifications and transcriptional induction in dentate gyrus granule neurons. Given that both N-methyl-D-aspartate (NMDA) receptors and the extracellular signal-regulated kinases (ERK) 1/2 signalling pathway are involved in neuroplasticity processes underlying learning and memory, we investigated in rats and mice whether these signalling pathways regulate chromatin modifications and transcriptional events participating in the acquisition of the immobility response. We found that: (i) forced swimming evoked a transient increase in the number of phospho-acetylated histone H3-positive [P(Ser10)-Ac(Lys14)-H3(+)] neurons specifically in the middle and superficial aspects of the dentate gyrus granule cell layer; (ii) antagonism of NMDA receptors and inhibition of ERK1/2 signalling blocked forced swimming-induced histone H3 phospho-acetylation and the acquisition of the behavioural immobility response; (iii) double knockout (DKO) of the histone H3 kinase mitogen- and stress-activated kinases (MSK) 1/2 in mice completely abolished the forced swimming-induced increases in histone H3 phospho-acetylation and c-Fos induction in dentate granule neurons and the behavioural immobility response; (iv) blocking mineralocorticoid receptors, known not to be involved in behavioural immobility in the forced swim test, did not affect forced swimming-evoked histone H3 phospho-acetylation in dentate neurons; and (v) the pharmacological manipulations and gene deletions did not affect behaviour in the initial forced swim test. We conclude that the forced swimming-induced behavioural immobility response requires histone H3 phospho-acetylation and c-Fos induction in distinct dentate granule neurons through recruitment of the NMDA/ERK/MSK 1/2 pathway.

  1. Enterovirus Control of Translation and RNA Granule Stress Responses.

    Science.gov (United States)

    Lloyd, Richard E

    2016-03-30

    Enteroviruses such as poliovirus (PV) and coxsackievirus B3 (CVB3) have evolved several parallel strategies to regulate cellular gene expression and stress responses to ensure efficient expression of the viral genome. Enteroviruses utilize their encoded proteinases to take over the cellular translation apparatus and direct ribosomes to viral mRNAs. In addition, viral proteinases are used to control and repress the two main types of cytoplasmic RNA granules, stress granules (SGs) and processing bodies (P-bodies, PBs), which are stress-responsive dynamic structures involved in repression of gene expression. This review discusses these processes and the current understanding of the underlying mechanisms with respect to enterovirus infections. In addition, the review discusses accumulating data suggesting linkage exists between RNA granule formation and innate immune sensing and activation.

  2. Linking granulation performance with residence time and granulation liquid distributions in twin-screw granulation: An experimental investigation

    DEFF Research Database (Denmark)

    Kumar, Ashish; Alakarjula, Maija; Vanhoorne, Valérie

    2016-01-01

    Twin-screw granulation is a promising wet granulation technique for the continuous manufacturing of pharmaceutical solid dosage forms. A twin screw granulator displays a short residence time. Thus, the solid-liquid mixing must be achieved quickly by appropriate arrangement of transport and kneading...

  3. The Proteomic Analysis of Pancreatic Exocrine Insufficiency Protein Marker in Type 2 Diabetes Mellitus Patients

    Science.gov (United States)

    Srihardyastutie, Arie; Soeatmadji, DW; Fatchiyah; Aulanni'am

    2018-01-01

    Type 2 Diabetes Mellitus (T2D) is the vast majority case of diabetes. Patient with T2D is at higher risk for developing acute or chronic pancreatitis. Prolonged hyperglycemia results in damages to tissue, which also causes dysfunctions of some organ systems, including enzyme or hormone secretions. Commonly, dysfunction or insufficiency of pancreatic exocrine is evaluated by increasing activity of serum pancreatic enzyme, such as amylase and lipase. Although incidence of pancreatitis was found in Indonesian T2D, the pathogenic mechanism still unclear. The aim of this study was to characterize the marker protein that indicated the correlation of pancreatic exocrine insufficiency with progression of T2D. Proteomic analysis using LC-MS/MS was used in identification and characterization of protein marker which indicates insufficiency pancreatic exocrine. First step, protein profile was analyzed by SDS-PAGE methods using serum sample of T2D compared with normal or healthy control, as negative control, and pancreatitis patients, as positive control. Protein with 18 kDa was found as a candidate protein marker which indicated the pancreatic exocrine insufficiency in T2D. The further identification of that protein using LC-MS/MS showed 4 peptide fragments. In silico analysis of the peptide fragment indicated the correlation of pancreatic exocrine insufficiency with progression of T2D was METTL10 - methyltransferase like protein-10.

  4. Multidimensional modelling of anaerobic granules

    DEFF Research Database (Denmark)

    Picioreanu, C.; Batstone, Damien J.; van Loosdrecht, M.C.M.

    2005-01-01

    A multispecies, two- and three-dimensional model was developed, based on a previously published planar biofilm model, and the biochemical structure of the ADM1. Several soluble substrates diffuse and react in the granule. Local pH is calculated from acid-base equilibria and charge balance. The mo...

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Bert Hölldobler

    Full Text Available 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.

  7. Gene delivery to pancreatic exocrine cells in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Houbracken Isabelle

    2012-10-01

    Full Text Available Abstract Background Effective gene transfer to the pancreas or to pancreatic cells has remained elusive although it is essential for studies of genetic lineage tracing and modulation of gene expression. Different transduction methods and viral vectors were tested in vitro and in vivo, in rat and mouse pancreas. Results For in vitro transfection/transduction of rat exocrine cells lipofection reagents, adenoviral vectors, and Mokola- and VSV-G pseudotyped lentiviral vectors were used. For in vivo transduction of mouse and rat pancreas adenoviral vectors and VSV-G lentiviral vectors were injected into the parenchymal tissue. Both lipofection of rat exocrine cell cultures and transduction with Mokola pseudotyped lentiviral vectors were inefficient and resulted in less than 4% EGFP expressing cells. Adenoviral transduction was highly efficient but its usefulness for gene delivery to rat exocrine cells in vitro was hampered by a drastic increase in cell death. In vitro transduction of rat exocrine cells was most optimal with VSV-G pseudotyped lentiviral vectors, with stable transgene expression, no significant effect on cell survival and about 40% transduced cells. In vivo, pancreatic cells could not be transduced by intra-parenchymal administration of lentiviral vectors in mouse and rat pancreas. However, a high efficiency could be obtained by adenoviral vectors, resulting in transient transduction of mainly exocrine acinar cells. Injection in immune-deficient animals diminished leukocyte infiltration and prolonged transgene expression. Conclusions In summary, our study remarkably demonstrates that transduction of pancreatic exocrine cells requires lentiviral vectors in vitro but adenoviral vectors in vivo.

  8. Exocrine dysfunction correlates with endocrinal impairment of pancreas in Type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    H R Prasanna Kumar

    2018-01-01

    Full Text Available Background: Diabetes mellitus (DM is a chronic abnormal metabolic condition, which manifests elevated blood sugar level over a prolonged period. The pancreatic endocrine system generally gets affected during diabetes, but often abnormal exocrine functions are also manifested due to its proximity to the endocrine system. Fecal elastase-1 (FE-1 is found to be an ideal biomarker to reflect the exocrine insufficiency of the pancreas. Aim: The aim of this study was conducted to assess exocrine dysfunction of the pancreas in patients with type-2 DM (T2DM by measuring FE levels and to associate the level of hyperglycemia with exocrine pancreatic dysfunction. Methodology: A prospective, cross-sectional comparative study was conducted on both T2DM patients and healthy nondiabetic volunteers. FE-1 levels were measured using a commercial kit (Human Pancreatic Elastase ELISA BS 86-01 from Bioserv Diagnostics. Data analysis was performed based on the important statistical parameters such as mean, standard deviation, standard error, t-test-independent samples, and Chi-square test/cross tabulation using SPSS for Windows version 20.0. Results: Statistically nonsignificant (P = 0.5051 relationship between FE-1 deficiency and age was obtained, which implied age as a noncontributing factor toward exocrine pancreatic insufficiency among diabetic patients. Statistically significant correlation (P = 0.003 between glycated hemoglobin and FE-1 levels was also noted. The association between retinopathy (P = 0.001 and peripheral pulses (P = 0.001 with FE-1 levels were found to be statistically significant. Conclusion: This study validates the benefit of FE-1 estimation, as a surrogate marker of exocrine pancreatic insufficiency, which remains unmanifest and subclinical.

  9. Exocrine Dysfunction Correlates with Endocrinal Impairment of Pancreas in Type 2 Diabetes Mellitus.

    Science.gov (United States)

    Prasanna Kumar, H R; Gowdappa, H Basavana; Hosmani, Tejashwi; Urs, Tejashri

    2018-01-01

    Diabetes mellitus (DM) is a chronic abnormal metabolic condition, which manifests elevated blood sugar level over a prolonged period. The pancreatic endocrine system generally gets affected during diabetes, but often abnormal exocrine functions are also manifested due to its proximity to the endocrine system. Fecal elastase-1 (FE-1) is found to be an ideal biomarker to reflect the exocrine insufficiency of the pancreas. The aim of this study was conducted to assess exocrine dysfunction of the pancreas in patients with type-2 DM (T2DM) by measuring FE levels and to associate the level of hyperglycemia with exocrine pancreatic dysfunction. A prospective, cross-sectional comparative study was conducted on both T2DM patients and healthy nondiabetic volunteers. FE-1 levels were measured using a commercial kit (Human Pancreatic Elastase ELISA BS 86-01 from Bioserv Diagnostics). Data analysis was performed based on the important statistical parameters such as mean, standard deviation, standard error, t -test-independent samples, and Chi-square test/cross tabulation using SPSS for Windows version 20.0. Statistically nonsignificant ( P = 0.5051) relationship between FE-1 deficiency and age was obtained, which implied age as a noncontributing factor toward exocrine pancreatic insufficiency among diabetic patients. Statistically significant correlation ( P = 0.003) between glycated hemoglobin and FE-1 levels was also noted. The association between retinopathy ( P = 0.001) and peripheral pulses ( P = 0.001) with FE-1 levels were found to be statistically significant. This study validates the benefit of FE-1 estimation, as a surrogate marker of exocrine pancreatic insufficiency, which remains unmanifest and subclinical.

  10. Exocrine cell-derived microparticles in response to lipopolysaccharide promote endocrine dysfunction in cystic fibrosis.

    Science.gov (United States)

    Constantinescu, Andrei Alexandru; Gleizes, Céline; Alhosin, Mahmoud; Yala, Elhassan; Zobairi, Fatiha; Leclercq, Alexandre; Stoian, Gheorghe; Mitrea, Ioan Liviu; Prévost, Gilles; Toti, Florence; Kessler, Laurence

    2014-03-01

    Diabetes in cystic fibrosis (CF) is a result of exocrine pancreas alteration followed by endocrine dysfunction at a later stage. Microparticles (MPs) are plasma membrane fragments shed from stimulated or damaged cells that act as cellular effectors. Our aim was to identify a new form of interaction between exocrine and endocrine pancreatic cells mediated by exocrine MPs, in the context of recurrent infection in CF. MPs from either human exocrine CFTRΔF508-mutated (CFPAC-1) cells or exocrine normal pancreatic (PANC-1) cells were collected after treatment by LPS from Pseudomonas aeruginosa and applied to rat endocrine normal insulin-secreting RIN-m5F cells. MP membrane integration in target cells was established by confocal microscopy and flow cytometry using PKH26 lipid probe. Apoptosis, lysosomal activity, insulin secretion were measured after 18 h. MP-mediated NF-κB activation was measured in HEK-Blue reporter cells by SEAP reporter gene system and in RIN-m5F cells by Western blot. In endocrine normal cells, CFTR inhibition was achieved using Inhibitor-172. Compared to PANC-1, MPs from CFPAC-1 significantly reduced insulin secretion and lysosomal activity in RIN-m5F. MPs induced NF-κB activation by increasing the level of IκB phosphorylation. Moreover, the inhibition of NF-κB activation using specific inhibitors was associated with a restored insulin secretion. Interestingly, CFTR inhibition in normal RIN-m5F cells promoted apoptosis and decreased insulin secretion. During recurrent infections associated with CF, exocrine MPs may contribute to endocrine cell dysfunction via NF-κB pathways. Membrane CFTR dysfunction is associated with decreased insulin secretion. © 2013. Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society. All rights reserved.

  11. Constitutively polarized granules prime KHYG-1 NK cells.

    Science.gov (United States)

    Suck, Garnet; Branch, Donald R; Aravena, Paola; Mathieson, Mark; Helke, Simone; Keating, Armand

    2006-09-01

    The major mechanism for NK cell lysis of tumor cells is granule-mediated cytotoxicity. Polarization of granules is a prelude to the release of their cytotoxic contents in response to target-cell binding. We describe the novel observation of constitutive granule polarization in the cytotoxic NK cell line, KHYG-1. Continuous degranulation of KHYG-1 cells, however, does not occur and still requires target-cell contact. Disruption of microtubules with colcemid is sufficient to disperse the granules in KHYG-1 and significantly decreases cytotoxicity. A similar effect is not obtained by inhibiting extracellular signal-related kinase 2 (ERK2), the most distal kinase investigated in the cytolytic pathway. Disruption of microtubules significantly down-regulates activation receptors, NKp44 and NKG2D, implicating them as potential microtubule-trafficking receptors. Such changes in upstream receptor expression may have caused deactivation of ERK2, since NKG2D cross-linking also leads to receptor down-regulation and diminished ERK phosphorylation. Thus, a functional role for NKG2D in KHYG-1 cytotoxicity is demonstrated. Moreover, the novel primed state may contribute to the high cytotoxicity exhibited by KHYG-1.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Philip D. Hardt

    2011-01-01

    Full Text Available 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.

  14. Distorted secretory granule composition in mast cells with multiple protease deficiency.

    Science.gov (United States)

    Grujic, Mirjana; Calounova, Gabriela; Eriksson, Inger; Feyerabend, Thorsten; Rodewald, Hans-Reimer; Tchougounova, Elena; Kjellén, Lena; Pejler, Gunnar

    2013-10-01

    Mast cells are characterized by an abundance of secretory granules densely packed with inflammatory mediators such as bioactive amines, cytokines, serglycin proteoglycans with negatively charged glycosaminoglycan side chains of either heparin or chondroitin sulfate type, and large amounts of positively charged proteases. Despite the large biological impact of mast cell granules and their contents on various pathologies, the mechanisms that regulate granule composition are incompletely understood. In this study, we hypothesized that granule composition is dependent on a dynamic electrostatic interrelationship between different granule compounds. As a tool to evaluate this possibility, we generated mice in which mast cells are multideficient in a panel of positively charged proteases: the chymase mouse mast cell protease-4, the tryptase mouse mast cell protease-6, and carboxypeptidase A3. Through a posttranslational effect, mast cells from these mice additionally lack mouse mast cell protease-5 protein. Mast cells from mice deficient in individual proteases showed normal morphology. In contrast, mast cells with combined protease deficiency displayed a profound distortion of granule integrity, as seen both by conventional morphological criteria and by transmission electron microscopy. An assessment of granule content revealed that the distorted granule integrity in multiprotease-deficient mast cells was associated with a profound reduction of highly negatively charged heparin, whereas no reduction in chondroitin sulfate storage was observed. Taken together with previous findings showing that the storage of basic proteases conversely is regulated by anionic proteoglycans, these data suggest that secretory granule composition in mast cells is dependent on a dynamic interrelationship between granule compounds of opposite electrical charge.

  15. Nucleoli and stress granules: connecting distant relatives.

    Science.gov (United States)

    Mahboubi, Hicham; Stochaj, Ursula

    2014-10-01

    Nucleoli and cytoplasmic stress granules (SGs) are subcellular compartments that modulate the response to endogenous and environmental signals to control cell survival. In our opinion, nucleoli and SGs are functionally linked; they are distant relatives that combine forces when cellular homeostasis is threatened. Several lines of evidence support this idea; nucleoli and SGs share molecular building blocks, are regulated by common signaling pathways and communicate when vital cellular functions become compromised. Together, nucleoli and SGs orchestrate physiological responses that are directly relevant to stress and human health. As both compartments have established roles in neurodegenerative diseases, cancer and virus infections, we propose that these conditions will benefit from therapeutic interventions that target simultaneously nucleoli and SGs. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Mechanism of the formation of hollow spherical granules using a high shear granulator.

    Science.gov (United States)

    Asada, Takumi; Nishikawa, Mitsunori; Ochiai, Yasushi; Noguchi, Shuji; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

    2018-05-30

    Recently, we have developed a novel granulation technology to manufacture hollow spherical granules (HSGs) for controlled-release formulations; however, the mechanism of the granulation is still unclear. The aim of this study is to determine the mechanism of the formation of the HSGs using a high shear granulator. Samples of granulated material were collected at various times during granulation and were investigated using scanning electron microscope and X-ray computed tomography. It was observed that the granulation proceeded by drug layering to the polymer, followed by formation of a hollow in the granule. In addition, it was also found that generation of a crack in the adhered drug layer and air flow into the granules might be involved in forming the hollow in the structure. Observation of the granulation of formulations with different types of drugs and polymers indicated that negative pressure in the granules occurred and the granules caved in when the hollow was formed. The hollow-forming speed and the shell density of the hollow granules depended on the particular drug and polymer. Taken together, the granulation mechanism of HSGs was determined and this information will be valuable for HSGs technology development. Copyright © 2018 Elsevier B.V. All rights reserved.

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

    NARCIS (Netherlands)

    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

    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

  18. Pancreatic Endocrine and Exocrine Function in Children following Near-Total Pancreatectomy for Diffuse Congenital Hyperinsulinism

    Science.gov (United States)

    Arya, Ved Bhushan; Senniappan, Senthil; Demirbilek, Huseyin; Alam, Syeda; Flanagan, Sarah E.; Ellard, Sian; Hussain, Khalid

    2014-01-01

    Context Congenital hyperinsulinism (CHI), the commonest cause of persistent hypoglycaemia, has two main histological subtypes: diffuse and focal. Diffuse CHI, if medically unresponsive, is managed with near-total pancreatectomy. Post-pancreatectomy, in addition to persistent hypoglycaemia, there is a very high risk of diabetes mellitus and pancreatic exocrine insufficiency. Setting International referral centre for the management of CHI. Patients Medically unresponsive diffuse CHI patients managed with near-total pancreatectomy between 1994 and 2012. Intervention Near-total pancreatectomy. Main Outcome Measures Persistent hypoglycaemia post near-total pancreatectomy, insulin-dependent diabetes mellitus, clinical and biochemical (faecal elastase 1) pancreatic exocrine insufficiency. Results Of more than 300 patients with CHI managed during this time period, 45 children had medically unresponsive diffuse disease and were managed with near-total pancreatectomy. After near-total pancreatectomy, 60% of children had persistent hypoglycaemia requiring medical interventions. The incidence of insulin dependent diabetes mellitus was 96% at 11 years after surgery. Thirty-two patients (72%) had biochemical evidence of severe pancreatic exocrine insufficiency (Faecal elastase 1pancreatectomy is very unsatisfactory. The incidence of persistent hypoglycaemia and insulin-dependent diabetes mellitus is very high. The presence of clinical rather than biochemical pancreatic exocrine insufficiency should inform decisions about pancreatic enzyme supplementation. PMID:24840042

  19. Attenuation of endocrine-exocrine pancreatic communication in type 2 diabetes: pancreatic extracellular matrix ultrastructural abnormalities.

    Science.gov (United States)

    Hayden, Melvin R; Patel, Kamlesh; Habibi, Javad; Gupta, Deepa; Tekwani, Seema S; Whaley-Connell, Adam; Sowers, James R

    2008-01-01

    Ultrastructural observations reveal a continuous interstitial matrix connection between the endocrine and exocrine pancreas, which is lost due to fibrosis in rodent models and humans with type 2 diabetes mellitus (T2DM). Widening of the islet-exocrine interface appears to result in loss of desmosomes and adherens junctions between islet and acinar cells and is associated with hypercellularity consisting of pericytes and inflammatory cells in T2DM pancreatic tissue. Organized fibrillar collagen was closely associated with pericytes, which are known to differentiate into myofibroblasts-pancreatic stellate cells. Of importance, some pericyte cellular processes traverse both the connecting islet-exocrine interface and the endoacinar interstitium of the exocrine pancreas. Loss of cellular paracrine communication and extracellular matrix remodeling fibrosis in young animal models and humans may result in a dysfunctional insulino-acinar-ductal-incretin gut hormone axis, resulting in pancreatic insufficiency and glucagon-like peptide deficiency, which are known to exist in prediabetes and overt T2DM in humans.

  20. Zinc status in chronic pancreatitis and its relationship with exocrine and endocrine insufficiency.

    Science.gov (United States)

    Girish, Banavara Narasimhamurthy; Rajesh, Gopalakrishna; Vaidyanathan, Kannan; Balakrishnan, Vallath

    2009-11-05

    A major role of the pancreas in zinc homeostasis has been suggested. To assess erythrocyte zinc status in chronic pancreatitis and to correlate it with pancreatic exocrine and endocrine insufficiency. One hundred and one patients with chronic pancreatitis (34 alcoholic chronic pancreatitis, 67 tropical chronic pancreatitis) were prospectively studied. Disease characteristics and imaging features were recorded. Erythrocyte zinc was estimated by flame atomic absorption spectrophotometry. Exocrine insufficiency was assessed using polyclonal antibody ELISA for pancreatic stool elastase1. Endocrine insufficiency was assessed by serum glucose levels and insulin requirement. Erythrocyte zinc was significantly lower in chronic pancreatitis patients than in the controls (26.5+/-9.5 microg/g Hb vs. 38.0+/-6.6 microg/g Hb; Ppancreatitis than in alcoholic chronic pancreatitis (25.0+/-10.4 microg/g Hb vs. 29.6+/-6.5 microg/g Hb, P=0.001). In chronic pancreatitis patients who had exocrine insufficiency, erythrocyte zinc positively correlated with stool elastase1 (r=0.587, Ppancreatitis patients, and that zinc deficiency correlates with exocrine and endocrine insufficiency. Further studies may clarify the possible benefits of zinc supplementation in chronic pancreatitis.

  1. Exocrine pancreatic insufficiency in the Eurasian dog breed - inheritance and exclusion of two candidate genes

    DEFF Research Database (Denmark)

    Proschowsky, Helle Friis; Fredholm, Merete

    2007-01-01

    Exocrine pancreatic insufficiency is considered an inherited disease in several dog breeds. Affected dogs show polyphagia, weight loss and voluminous faeces of light colour due to the lack of pancreatic enzymes. In the study described herein, we performed a segregation analysis using the SINGLES ...

  2. The distribution of exocrine glands in Lepeophtheirus salmonis and Caligus elongatus (Copepoda: Caligidae)

    NARCIS (Netherlands)

    Bell, S.; Bron, J.E.; Sommerville, C.

    2000-01-01

    The morphology, function and distribution of exocrine glands of copepods have rarely been studied in detail and almost nothing is known about them in the sea lice species L. salmonis and C. elongatus. This study utilised a novel application of a light-microscopy staining technique to reveal a

  3. Increased accuracy of starch granule type quantification using mixture distributions

    OpenAIRE

    Tanaka, Emi; Ral, Jean-Phillippe F.; Li, Sean; Gaire, Raj; Cavanagh, Colin R.; Cullis, Brian R.; Whan, Alex

    2017-01-01

    Background The proportion of granule types in wheat starch is an important characteristic that can affect its functionality. It is widely accepted that granule types are either large, disc-shaped A-type granules or small, spherical B-type granules. Additionally, there are some reports of the tiny C-type granules. The differences between these granule types are due to its carbohydrate composition and crystallinity which is highly, but not perfectly, correlated with the granule size. A majority...

  4. Prospective assessment of the influence of pancreatic cancer resection on exocrine pancreatic function.

    Science.gov (United States)

    Sikkens, E C M; Cahen, D L; de Wit, J; Looman, C W N; van Eijck, C; Bruno, M J

    2014-01-01

    Exocrine insufficiency frequently develops in patients with pancreatic cancer owing to tumour ingrowth and pancreatic duct obstruction. Surgery might restore this function by removing the primary disease and restoring duct patency, but it may also have the opposite effect, as a result of resection of functional parenchyma and anatomical changes. This study evaluated the course of pancreatic function, before and after pancreatic resection. This prospective cohort study included patients with tumours in the pancreatic region requiring pancreatic resection in a tertiary referral centre between March 2010 and August 2012. Starting before surgery, exocrine function was determined monthly by measuring faecal elastase 1 levels (normal value over 0.200 µg per g faeces). Endocrine function, steatorrhoea-related symptoms and bodyweight were also evaluated before and after surgery. Subjects were followed from diagnosis until 6 months after surgery, or until death. Twenty-nine patients were included, 12 with pancreatic cancer, 14 with ampullary carcinoma and three with bile duct carcinoma (median tumour size 2.6 cm). Twenty-six patients underwent pancreaticoduodenectomy and three distal pancreatectomy. Thirteen patients had exocrine insufficiency at preoperative diagnosis. After a median follow-up of 6 months, this had increased to 24 patients. Diabetes was present in seven patients at diagnosis, and developed in one additional patient within 1 month after surgery. Most patients with tumours in the pancreatic region requiring pancreatic resection either had exocrine insufficiency at diagnosis or became exocrine-insufficient soon after surgical resection. © 2013 BJS Society Ltd. Published by John Wiley & Sons Ltd.

  5. Exocrine pancreas glutamate secretion help to sustain enterocyte nutritional needs under protein restriction.

    Science.gov (United States)

    Araya, S; Kuster, E; Gluch, D; Mariotta, L; Lutz, C; Reding, T V; Graf, R; Verrey, F; Camargo, S M R

    2018-04-01

    Glutamine (Gln) is the most concentrated amino acid in blood and considered conditionally essential. Its requirement is increased during physiological stress, such as malnutrition or illness, despite its production by muscle and other organs. In the malnourished state, Gln has been suggested to have a trophic effect on the exocrine pancreas and small intestine. However, the Gln transport capacity, the functional relationship of these two organs, and the potential role of the Gln-glutamate (Glu) cycle are unknown. We observed that pancreatic acinar cells express lower levels of Glu than Gln transporters. Consistent with this expression pattern, the rate of Glu influx into acinar cells was approximately sixfold lower than that of Gln. During protein restriction, acinar cell glutaminase expression was increased and Gln accumulation was maintained. Moreover, Glu secretion by acinar cells into pancreatic juice and thus into the lumen of the small intestine was maintained. In the intestinal lumen, Glu absorption was preserved and Glu dehydrogenase expression was augmented, potentially providing the substrates for increasing energy production via the TCA cycle. Our findings suggest that one mechanism by which Gln exerts a positive effect on exocrine pancreas and small intestine involves the Gln metabolism in acinar cells and the secretion of Glu into the small intestine lumen. The exocrine pancreas acinar cells not only avidly accumulate Gln but metabolize Gln to generate energy and to synthesize Glu for secretion in the pancreatic juice. Secreted Glu is suggested to play an important role during malnourishment in sustaining small intestinal homeostasis. NEW & NOTEWORTHY Glutamine (Gln) has been suggested to have a trophic effect on exocrine pancreas and small intestine in malnourished states, but the mechanism is unknown. In this study, we suggest that this trophic effect derives from an interorgan relationship between exocrine pancreas and small intestine for Gln

  6. rab3 mediates cortical granule exocytosis in the sea urchin egg.

    Science.gov (United States)

    Conner, S; Wessel, G M

    1998-11-15

    Egg activation at fertilization in the sea urchin results in the exocytosis of approximately 15,000 cortical granules that are docked at the plasma membrane. Previously, we reported that several integral membrane proteins modeled in the SNARE hypothesis, synaptotagmin, VAMP, and syntaxin, in addition to a small GTPase of the ras superfamily, rab3, were present on cortical granules (Conner, S., Leaf, D., and Wessel, G., Mol. Reprod. Dev. 48, 1-13, 1997). Here we report that rab3 is associated with cortical granules throughout oogenesis, during cortical granule translocation, and while docked at the egg plasma membrane. Following cortical granule exocytosis, however, rab3 reassociates with a different population of vesicles, at least some of which are of endocytic origin. Because of its selective association with cortical granules in eggs and oocytes, we hypothesize that rab3 functions in cortical granule exocytosis. To test this hypothesis, we used a strategy of interfering with rab3 function by peptide competition with its effector domain, a conserved region within specific rab types. We first identified the effector domain sequence in Lytechinus variegatus eggs and find the sequence 94% identical to the effector domain of rab3 in Stronglocentrotus purpuratus. Then, with synthetic peptides to different regions of the rab3 protein, we find that cortical granule exocytosis is inhibited in eggs injected with effector domain peptides, but not with peptides from the hypervariable region or with a scrambled effector peptide. Additionally, effector-peptide-injected eggs injected with IP3 are blocked in their ability to exocytose cortical granules, suggesting that the inhibition is directly on the membrane fusion event and not the result of interference with the signal transduction mechanism leading to calcium release. We interpret these results to mean that rab3 functions in the regulation of cortical granule exocytosis following vesicle docking. Copyright 1998 Academic

  7. Stimulus-secretion coupling in the developing exocrine pancreas

    International Nuclear Information System (INIS)

    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) α-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 125 I-CCK octapeptide specifically bound/cell equivalent or a change in the affinity of binding. Light microscopic autoradiography revealed a similar 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 ++ concentration, [Ca ++ ]c, in the embryonic pancreas, 45 Ca ++ efflux from tracer-loaded lobules was measured. Efflux of 45 Ca ++ from both embryonic and neonatal pancreas was comparably increased in the presence of CCK

  8. Sequestration of highly expressed mRNAs in cytoplasmic granules, P-bodies, and stress granules enhances cell viability.

    Directory of Open Access Journals (Sweden)

    Anna Lavut

    Full Text Available Transcriptome analyses indicate that a core 10%-15% of the yeast genome is modulated by a variety of different stresses. However, not all the induced genes undergo translation, and null mutants of many induced genes do not show elevated sensitivity to the particular stress. Elucidation of the RNA lifecycle reveals accumulation of non-translating mRNAs in cytoplasmic granules, P-bodies, and stress granules for future regulation. P-bodies contain enzymes for mRNA degradation; under stress conditions mRNAs may be transferred to stress granules for storage and return to translation. Protein degradation by the ubiquitin-proteasome system is elevated by stress; and here we analyzed the steady state levels, decay, and subcellular localization of the mRNA of the gene encoding the F-box protein, UFO1, that is induced by stress. Using the MS2L mRNA reporter system UFO1 mRNA was observed in granules that colocalized with P-bodies and stress granules. These P-bodies stored diverse mRNAs. Granules of two mRNAs transported prior to translation, ASH1-MS2L and OXA1-MS2L, docked with P-bodies. HSP12 mRNA that gave rise to highly elevated protein levels was not observed in granules under these stress conditions. ecd3, pat1 double mutants that are defective in P-body formation were sensitive to mRNAs expressed ectopically from strong promoters. These highly expressed mRNAs showed elevated translation compared with wild-type cells, and the viability of the mutants was strongly reduced. ecd3, pat1 mutants also exhibited increased sensitivity to different stresses. Our interpretation is that sequestration of highly expressed mRNAs in P-bodies is essential for viability. Storage of mRNAs for future regulation may contribute to the discrepancy between the steady state levels of many stress-induced mRNAs and their proteins. Sorting of mRNAs for future translation or decay by individual cells could generate potentially different phenotypes in a genetically identical

  9. Exocrine pancreatic insufficiency in type 1 and type 2 diabetes mellitus: do we need to treat it? A systematic review.

    Science.gov (United States)

    Zsóri, Gábor; Illés, Dóra; Terzin, Viktória; Ivány, Emese; Czakó, László

    2018-05-17

    The exocrine and endocrine pancreata are very closely linked both anatomically and physiologically. Abdominal symptoms such as nausea, bloating, diarrhea, steatorrhea, and weight loss can often occur in diabetic patients. Impairments of the exocrine pancreatic function seem to be a frequent complication of diabetes mellitus; however, they are largely overlooked. The aim of this paper is to provide an overview of the current concepts of exocrine pancreatic insufficiency (PEI) in diabetes mellitus. The prevalence and symptoms of PEI in diabetes mellitus, the pathomechanism, and difficulties of diagnosis and therapy of PEI are summarized in this systematic review. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  10. Medical image of the week: granulation tissue

    Directory of Open Access Journals (Sweden)

    Ganesh A

    2014-03-01

    Full Text Available A 57 year old woman presented with a tickling sensation in the back of throat and intermittent bleeding from the healing stoma one month after decannulation of her tracheostomy tube. On bronchoscopy a granuloma with surrounding granulation tissue was present in the subglottic space (Figure 1. Argon plasma coagulation (APC was performed to cauterize the granulation tissue (Figure 2. Formation of granulation tissue after tracheostomy is a common complication which can result in tracheal stenosis. APC and electrocautery using flexible bronchoscopy has been shown to safely and effectively remove the granulation tissue.

  11. Distribution of binder in granules produced by means of twin screw granulation

    DEFF Research Database (Denmark)

    Fonteyne, Margot; Fussell, Andrew Luke; Vercruysse, Jurgen

    2014-01-01

    According to the quality by design principle processes may not remain black-boxes and full process understanding is required. The granule size distribution of granules produced via twin screw granulation is often found to be bimodal. The aim of this study was to gain a better understanding...

  12. The paradox of high shear granulation : the formation of non-homogeneous granules

    NARCIS (Netherlands)

    Dries, Kaspar van den

    2004-01-01

    Wet granulation is a process used for the particle size enlargement of primary powders. The mixing of a liquid with the powder glues the primary particles together, which results in the formation of the granules. The mixing action can be performed in many ways, like tumbling (drum granulation),

  13. APPLICATION OF GRANULATION TECHNOLOGY IN VARIOUS INDUSTRIES

    Directory of Open Access Journals (Sweden)

    B. V. YEGOROV

    2017-10-01

    Full Text Available Science and practice proved the high efficiency of granulated mixed fodders. This article presents an overview of granulation technologies for various industries. This article discusses the application of granulation technologies in various industries. The processes of granulation are mass technological processes currently used in a wide range of industries: feed industry, food industry, pharmaceutical industry, fertilizer production, polyethylene, metal production, mining, etc. A wide range of different materials are granulated, including chemicals, iron ore, mixed fodder, and much more. Granulation is a process of pressing or shaping a material in the form of granulesGranulation is widely used in the production of pigments, dyes, synthetic detergents, catalysts, plastics, soot, chemical reagents, etc. The use of granular raw materials in the metallurgical industry helps not only to mechanize processes, but also to increase their intensity by increasing the contact surface of interacting media. Granular fertilizers retain their properties for a long time. In the mining industry, granulation processes are used at the stage of preparation and enrichment of raw materials and release of the finished product.  Particular attention is paid to the feed industry. Granulation allows to ensure stable homogeneity, to improve sanitary and hygienic parameters, to increase nutritional value, to increase the storage period, improve the physical properties. However, despite all the advantages, the existing granulation production lines have a relatively high productivity and, at the same time, a high energy intensity. In this regard, this article proposes a technology for improving the granulation of mixed fodders. According to a preliminary literary review, It should be concluded that improving the technology of the granulation process for feed production is a topical issue in the feed industry today. The development of technology for improving the

  14. Endocrine and exocrine pancreatic insufficiency after acute pancreatitis: long-term follow-up study.

    Science.gov (United States)

    Tu, Jianfeng; Zhang, Jingzhu; Ke, Lu; Yang, Yue; Yang, Qi; Lu, Guotao; Li, Baiqiang; Tong, Zhihui; Li, Weiqin; Li, Jieshou

    2017-10-27

    Patients could develop endocrine and exocrine pancreatic insufficiency after acute pancreatitis (AP), but the morbidity, risk factors and outcome remain unclear. The aim of the present study was to evaluate the incidence of endocrine and exocrine pancreatic insufficiency after AP and the risk factors of endocrine pancreatic insufficiency through a long-term follow-up investigation. Follow-up assessment of the endocrine and exocrine function was conducted for the discharged patients with AP episodes. Oral Glucose Tolerance Test (OGTT) and faecal elastase-1(FE-1) test were used as primary parameters. Fasting blood-glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin HBA1c, 2-h postprandial blood glucose (2hPG), Homa beta cell function index (HOMA-β), homeostasis model assessment of insulin resistance (HOMA-IR) and FE-1 were collected. Abdominal contrast-enhanced computed tomography (CECT) was performed to investigate the pancreatic morphology and the other related data during hospitalization was also collected. One hundred thirteen patients were included in this study and 34 of whom (30.1%) developed diabetes mellitus (DM), 33 (29.2%) suffered impaired glucose tolerance (IGT). Moreover, 33 patients (29.2%) developed mild to moderate exocrine pancreatic insufficiency with 100μg/gpancreatic insufficiency with FE-1pancreatic necrosis was significant higher than that in the non-pancreatic necrosis group (X 2  = 13.442,P = 0.001). The multiple logistic regression analysis showed that extent of pancreatic necrosisendocrine pancreatic insufficiency. HOMA-IR (P = 0.002, OR = 6.626), Wall-off necrosis (WON) (P = 0.013, OR = 184.772) were the risk factors. The integrated morbidity of DM and IGT after AP was 59.25%, which was higher than exocrine pancreatic insufficiency. 6.2% and 29.2% of patients developed severe and mild to moderate exocrine pancreatic insufficiency, respectively. The extent of pancreatic necrosis>50%, WON and insulin resistance were

  15. Bone mineral metabolism, bone mineral density, and body composition in patients with chronic pancreatitis and pancreatic exocrine insufficiency

    DEFF Research Database (Denmark)

    Haaber, Anne Birgitte; Rosenfalck, A M; Hansen, B

    2000-01-01

    Calcium and vitamin D homeostasis seem to be abnormal in patients with exocrine pancreatic dysfunction resulting from cystic fibrosis. Only a few studies have evaluated and described bone mineral metabolism in patients with chronic pancreatitis and pancreatic insufficiency....

  16. Coating of waste containing ceramic granules

    International Nuclear Information System (INIS)

    Neumann, W.; Kofler, O.

    1979-01-01

    Simulated high-level waste granules produced by fluidized-bed calcination were overcoated by chemical vapor deposition (CVD) with pyrocarbon and nickel in laboratory-scale experiments. Successful development enables pyrocrbon deposition at temperatures of 600 to 800 0 K. The coated granules have excellent properties for long-term waste storage

  17. Multiphase flow in spout fluidized bed granulators

    NARCIS (Netherlands)

    Buijtenen, van M.S.

    2011-01-01

    Spout fluidized beds are frequently used for the production of granules or particles through granulation, which are widely applied, for example, in the production of detergents, pharmaceuticals, food and fertilizers (M¨orl et al. 2007). Spout fluidized beds have a number of advantageous properties,

  18. Twin screw wet granulation: Binder delivery.

    Science.gov (United States)

    Saleh, Mohammed F; Dhenge, Ranjit M; Cartwright, James J; Hounslow, Michael J; Salman, Agba D

    2015-06-20

    The effects of three ways of binder delivery into the twin screw granulator (TSG) on the residence time, torque, properties of granules (size, shape, strength) and binder distribution were studied. The binder distribution was visualised through the transparent barrel using high speed imaging as well as quantified using offline technique. Furthermore, the effect of binder delivery and the change of screw configuration (conveying elements only and conveying elements with kneading elements) on the surface velocity of granules across the screw channel were investigated using particle image velocimetry (PIV). The binder was delivered in three ways; all solid binder incorporated with powder mixture, 50% of solid binder mixed with powder mixture and 50% mixed with water, all the solid binder dissolved in water. Incorporation of all solid binder with powder mixture resulted in the relatively longer residence time and higher torque, narrower granule size distribution, more spherical granules, weaker big-sized granules, stronger small-sized granules and better binder distribution compared to that in other two ways. The surface velocity of granules showed variation from one screw to another as a result of uneven liquid distribution as well as shown a reduction while introducing the kneading elements into the screw configuration. Copyright © 2015. Published by Elsevier B.V.

  19. CSR-1 and P granules suppress sperm-specific transcription in the C. elegans germline.

    Science.gov (United States)

    Campbell, Anne C; Updike, Dustin L

    2015-05-15

    Germ granules (P granules) in C. elegans are required for fertility and function to maintain germ cell identity and pluripotency. Sterility in the absence of P granules is often accompanied by the misexpression of soma-specific proteins and the initiation of somatic differentiation in germ cells. To investigate whether this is caused by the accumulation of somatic transcripts, we performed mRNA-seq on dissected germlines with and without P granules. Strikingly, we found that somatic transcripts do not increase in the young adult germline when P granules are impaired. Instead, we found that impairing P granules causes sperm-specific mRNAs to become highly overexpressed. This includes the accumulation of major sperm protein (MSP) transcripts in germ cells, a phenotype that is suppressed by feminization of the germline. A core component of P granules, the endo-siRNA-binding Argonaute protein CSR-1, has recently been ascribed with the ability to license transcripts for germline expression. However, impairing CSR-1 has very little effect on the accumulation of its mRNA targets. Instead, we found that CSR-1 functions with P granules to prevent MSP and sperm-specific mRNAs from being transcribed in the hermaphrodite germline. These findings suggest that P granules protect germline integrity through two different mechanisms, by (1) preventing the inappropriate expression of somatic proteins at the level of translational regulation, and by (2) functioning with CSR-1 to limit the domain of sperm-specific expression at the level of transcription. © 2015. Published by The Company of Biologists Ltd.

  20. Bombesin-stimulated serum immunoreactive trypsin in the different diagnosis between endocrine and exocrine tumors of the pancreas

    International Nuclear Information System (INIS)

    Bonora, G.; De Giorgio, R.; Toni, R.; Fanti, M.P.; Cariani, G.; Vezzadini, P.

    1987-01-01

    Bombesin administration was recently found to induce a marked increase in circulating immunoreactive trypsin (IRT), whose magnitude seems to reflect the functional capacity of pancreatic acinar cell mass. The purpose of the present study was to assess the effect of bombesin infusion on serum IRT concentration in patients with endocrine or exocrine tumors of the pancreas. Fifteen patients with pancreatic endocrine tumor, 17 patients with pancreatic exocrine carcinoma and 15 healty subjects were investigated. Serum IRT was measured by radioimmunoassay before and for 120 minutes after the start of bombesin infusion (9 ng/kg/min over 30 min). The integrated serum IRT response to bombesin administration in patients with endocrine tumor of the pancreas did not differ significantly from controls, but were significantly higher than in patients with exocrine carcinoma. In the latter the integrated IRT responses to bombesin infusion in patients with endocrine tumor can probably be explained by small tumor size and/or little invasion of the glandular parenchyma, resulting in an undetectable impairment of exocrine pancreatic function. The very low IRT responses in patients with exocrine carcinoma could reflect the presence of severe pancreatic damage. The results suggest that this newly proposed bombesin test may be useful in the preoperative differential diagnosis between endocrine and exocrine tumors of the pancreas

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

    Science.gov (United States)

    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.

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

    Science.gov (United States)

    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

  3. Remnant pancreatic parenchymal volume predicts postoperative pancreatic exocrine insufficiency after pancreatectomy.

    Science.gov (United States)

    Okano, Keisuke; Murakami, Yoshiaki; Nakagawa, Naoya; Uemura, Kenichiro; Sudo, Takeshi; Hashimoto, Yasushi; Kondo, Naru; Takahashi, Shinya; Sueda, Taijiro

    2016-03-01

    Pancreatectomy, including pancreatoduodenectomy and distal pancreatectomy, often causes postoperative pancreatic exocrine insufficiency (PEI). Our aim was to clarify a relationship between remnant pancreatic volume and postoperative PEI. A total of 227 patients who underwent pancreatoduodenectomy or distal pancreatectomy were enrolled in this study. All patients underwent a (13)C-labeled mixed triglyceride breath test to assess pancreatic exocrine function and abdominal dynamic computed tomography for assessing remnant pancreatic volume after pancreatectomy at a median of 7 months postoperatively. The percent (13)CO2 cumulative dose at 7 hours (% dose (13)C cum 7 h) pancreatectomy were performed in 174 (76.7%) and 53 (23.3%) patients, respectively. Of the 227 patients, 128 (56.3%) developed postoperative PEI. Postoperative % dose (13)C cum 7 h was strongly correlated with remnant pancreatic volume (r = .509, P pancreatectomy (P pancreatectomy. Remnant pancreatic volume may predict postoperative PEI in patients who undergo pancreatectomy. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Exocrine glands in the legs of the social wasp Vespula vulgaris.

    Science.gov (United States)

    Nijs, Catherine; Billen, Johan

    2015-09-01

    This study brings a survey of the exocrine glands in the legs of Vespula vulgaris wasps. We studied workers, males, virgin queens as well as mated queens. A variety of 17 glands is found in the different leg segments. Among these, five glands are novel exocrine structures for social insects (trochanter-femur gland, ventrodistal tibial gland, distal tibial sac gland, ventral tibial gland, and ventral tarsomere gland). Most leg glands are present in the three leg pairs of all castes. This may indicate a mechanical function. This is likely for the numerous glands that occur near the articulation between the various leg segments, where lubricant production may be expected. Other possible functions include antenna cleaning, acting as a hydraulic system, or pheromonal. Further research including leg-related behavioural observations and chemical analyses may help to clarify the functions of these glandular structures in the legs. Copyright © 2015 Elsevier Ltd. All rights reserved.

  5. Effect of acute irradiation on the exocrine secretion of the pancreas in the pig

    International Nuclear Information System (INIS)

    Corring, T.; Daburon, F.; Remy, J.

    1975-01-01

    Six fistulated pigs have been used in this experiment to study the effect on the exocrine pancreatic secretion of a partial acute irradiation at 600 rd and 800 rd. Whatever the dose, the irradiation provoked an immediate and temporary decrease of the pancreatic secretion. The normal values were reached after the 8th day post-irradiation. Furthermore, a direct effect on the synthesis of amylase and lipase was shown. The synthesis of trypsin and chymotrypsin was scarcely modified by irradiation. (orig.) [de

  6. Predictive factors of endocrine and exocrine insufficiency after resection of a benign tumour of the pancreas.

    Science.gov (United States)

    Neophytou, Hélène; Wangermez, Marc; Gand, Elise; Carretier, Michel; Danion, Jérôme; Richer, Jean-Pierre

    2018-04-01

    The aim of the present study is to evaluate the risk factors of endocrine and exocrine insufficiency occurring few years after pancreatic resections in a consecutive series of patients who underwent pancreatoduodenectomy (PD), left pancreatectomy (LP) or enucleation for benign neoplasms at a referral centre. Pancreatic exocrine insufficiency (PEI) was defined by the onset of steatorrhea associated with weight loss, and endocrine insufficiency was determinate by fasting plasma glucose. Association between pancreatic insufficiency and clinical, pathological, and perioperative features was studied using univariate and multivariate Cox regression analysis. A prospective cohort of 92 patients underwent PD (48%), LP (44%) or enucleation (8%) for benign tumours, from 2005 to 2016 in the University Hospital in Poitiers (France). The median follow-up was 68.6±42.4months. During the following, 54 patients developed exocrine insufficiency whereas 32 patients presented endocrine insufficiency. In the Cox model, a BMI>28kg/m 2 , being a man and presenting a metabolic syndrome were significantly associated with a higher risk to develop postoperative diabetes. The risks factors for the occurrence of PEI were preoperative chronic pancreatitis, a BMIpancreatic head, biological markers of chronic obstruction and fibrotic pancreas. Undergoing LP or enucleation were protective factors of PEI. Histological categories such as neuroendocrine tumours and cystadenomas were also associated with a decreased incidence of PEI. Men with metabolic syndrome and obesity should be closely followed-up for diabetes, and patients with obstructive tumours, pancreatic fibrosis or chronic pancreatitis require a vigilant follow up on their pancreatic exocrine function. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  7. Effect of Sodium Cyclamate on the Rat Fetal Exocrine Pancreas: a Karyometric and Stereological Study

    OpenAIRE

    MARTINS, Alex Tadeu; SANTOS, Fabiano de Sant`Ana dos; SCANNAVINO, Fabio Luiz Ferreira; PIRES, Juliana Rico; ZUZA, Elizangela Partata; PADOVANI JUNIOR, Joao Armando; AZOUBEL, Reinaldo; MATEO, Miguel Angel Sala Di; LOPES, Ruberval Armando

    2010-01-01

    The cyclamate, a sweetner substance derived from N-cyclo-hexyl-sulfamic acid, is largely utilized as a non-caloric artificial edulcorant in foods and beverages as well as in the pharmaceutical industry. The objective of this study was to evaluate karyometric and stereological alterations in the rat fetal pancreas resulting from the intraperitoneal administration of sodium cyclamate. The exocrine pancreas of ten fetuses of rats were evaluated, five treated and five controls chosen at random, i...

  8. THE STUDY OF THE KINETIC OF NATURAL ZEOLITE GRANULES GROWTH AT DIFFERENT WAYS OF GRANULATION

    Directory of Open Access Journals (Sweden)

    Rybachuk VD

    2016-12-01

    Full Text Available Introduction. Active substances and excipients used in the manufacture of medicines in tablet form, in most cases, have poor technological properties. This fact determines the need for prior granulation of mass before compression. Granulators of various sizes and designs, running on different modes, made the formation, growth and consolidation of the powder particles that lead to obtain pellets of different shapes and sizes. From the literature it is known that granulation leads to two forms of granules: isodiametric and nonisodiametric. The first group of particles forms has globular shape with a smooth surface and the proportion in which the length, thickness and height are about the same. They are usually made by fluidized bed granulation, spray drying, pelletizing and granulation in dragee pan. Granules of nonisodiametric form in which length is several times the width and height are made mostly by extrusion and compacting. The geometrical parameters of obtained granules are affected by the properties of raw materials, the granulation modes, type and amount of added humidifier and so on. The shape and size of granules, from a technological point of view, are the key factors that contribute, except organoleptic characteristics of the product, its technological properties such as particle size distribution, bulk volume, the ability of the material to shrinkage, porosity, fluidity, mechanical strength and so on. Properly selected for specific conditions granulation method is able to provide the finished product with the specified technological parameters depending on the needs. The aim of this work was to study the effect of granulation method and its conditions on the kinetics of growth of the natural zeolite granules and some quality characteristics of obtained granules. Material & methods. As objects of study served the natural zeolite pellets produced using 3%, 5%, 7% and 10% potato starch paste and solution of polyvinylpyrrolidone (PVP

  9. Influence of SPK with Enteric Drainage on the Pancreatic Exocrine Function in Diabetic Patients with Uremia

    Directory of Open Access Journals (Sweden)

    Guanghui Pei

    2017-01-01

    Full Text Available Objective. This study aimed to determine the use of fecal elastase in evaluating the effect of simultaneous pancreas–kidney transplantation with enteric drainage on the pancreatic exocrine function of diabetic patients with uremia. Methods. A total of 19 patients with simultaneous pancreas–kidney transplantation (SPK with enteric drainage, 31 diabetic patients with uremia (chronic renal failure (CRF, 22 diabetic patients with uremia who underwent renal transplantation (RT, and 20 normal individuals (CON were included in the study. Pancreatic exocrine insufficiency was determined using fecal elastase. Results. The fecal pancreatic elastase level in SPK patients with enteric drainage was 479 μg/g, which was significantly higher than 229 μg/g in CRF patients and 197 μg/g in RT patients. Using 200 μg/g as the established threshold, a reduced fecal pancreatic elastase level was found in 14/31 of CRF patients, 12/22 of RT patients, 1/19 of SPK patients with enteric drainage, and 1/20 of CON patients. The correlation analysis revealed a significant association between fecal elastase and glycosylated hemoglobin. Conclusions. The present study indicated that SPK with enteric drainage improves pancreatic endocrine and exocrine functions. Fecal elastase may be a clinically relevant means to determine the therapeutic effects.

  10. Increased biogenesis of glucagon-containing secretory granules and glucagon secretion in BIG3-knockout mice

    Directory of Open Access Journals (Sweden)

    Hongyu Li

    2015-03-01

    Conclusions: Together with our previous studies, the current data reveal a conserved role for BIG3 in regulating alpha- and beta-cell functions. We propose that BIG3 negatively regulates hormone production at the secretory granule biogenesis stage and that such regulatory mechanism may be used in secretory pathways of other endocrine cells.

  11. Polyhydroxyalkanoate (PHA) Granules Have no Phospholipids

    Science.gov (United States)

    Bresan, Stephanie; Sznajder, Anna; Hauf, Waldemar; Forchhammer, Karl; Pfeiffer, Daniel; Jendrossek, Dieter

    2016-01-01

    Polyhydroxybutyrate (PHB) granules, also designated as carbonosomes, are supra-molecular complexes in prokaryotes consisting of a PHB polymer core and a surface layer of structural and functional proteins. The presence of suspected phospholipids in the surface layer is based on in vitro data of isolated PHB granules and is often shown in cartoons of the PHB granule structure in reviews on PHB metabolism. However, the in vivo presence of a phospholipid layer has never been demonstrated. We addressed this topic by the expression of fusion proteins of DsRed2EC and other fluorescent proteins with the phospholipid-binding domain (LactC2) of lactadherin in three model organisms. The fusion proteins specifically localized at the cell membrane of Ralstonia eutropha but did not co-localize with PHB granules. The same result was obtained for Pseudomonas putida, a species that accumulates another type of polyhydroxyalkanoate (PHA) granules related to PHB. Notably, DsRed2EC-LactC2 expressed in Magnetospirillum gryphiswaldense was detected at the position of membrane-enclosed magnetosome chains and at the cytoplasmic membrane but not at PHB granules. In conclusion, the carbonosomes of representatives of α-proteobacteria, β-proteobacteria and γ-proteobacteria have no phospholipids in vivo and we postulate that the PHB/PHA granule surface layers in natural producers generally are free of phospholipids and consist of proteins only. PMID:27222167

  12. Regularities of formation of granules at granulation of powdered materials in drum devices

    International Nuclear Information System (INIS)

    Kelbaliyev, G.I; Samedli, V.M.

    2008-01-01

    Full text:Granulation of powdered materials in the presence of binding agent is widely used in the most multi-tankage productions of chemical, food, pharmaceutical, metallurgical and agrarian technology. Granulation of powdered materials with participation of liquid phase is carried out in screw, disk, plase-shaped and drum devices and also in devices with mixers. In all cases a formation and growth of granules takes place owing to wetting of separate particles of powder leading to agglomeration and coagulation of particles in their contact with each other. It is apparent that in early stage of granule formation a growth and formation of granules takes place owing to adherence of small particles and agglomerates to larger granules. The content of liquid phase owing to which are appeared adhesive, capillary and surface forces, keeping particles on surface of granule exerts an essential influence on process of granule formation. Besides composition of mixture, its moisture and physical-chemical properties of initial components a mixing frequency degree of filling and angle of inclination of the device, ratio of liquid and hard phases which defines finally qualitative characteristics of the process exert an essential influence on formation of granules as a result of agglomeration of particles of powder. Powder lamination on granule surface is as consequence of its consolidation whereas as a result of consolidation and compression, a binding agent containing in pores squeezed out to a surface, which increases a possibility and probability of further sticking of dry particles of powder. In all cases the further growth and completeness of form of granule is determined by distribution of concentration of binding agent in volume of granule, i.e. moisture content or moisture of granule surface

  13. Cigarette smoke-induced differential expression of the genes involved in exocrine function of the rat pancreas.

    Science.gov (United States)

    Wittel, Uwe A; Singh, Ajay P; Henley, Brandon J; Andrianifahanana, Mahefatiana; Akhter, Mohammed P; Cullen, Diane M; Batra, Surinder K

    2006-11-01

    Little is known about the molecular and biological aspects of the epidemiological association between smoking and pancreatic pathology, such as chronic pancreatitis and pancreatic cancer. Recently, we reported that tobacco smoke exposure induced morphological alterations in the rat pancreas. Here, we have investigated the alterations in the expression of genes associated with exocrine pancreatic function and cellular differentiation upon exposure to cigarette smoke. Female rats were exposed to environmental smoke inhalation for 2 d/wk (70 min/d) for 12 weeks. The expression profiles of trypsinogen, pancreas-specific trypsin inhibitor, cholecystokinin A receptor, cystic fibrosis transmembrane conductance regulator (CFTR), carbonic anhydrase, and Muc1 and Muc4 mucins transcripts were analyzed by RNA slot blot analysis. Muc4 expression was also examined by immunohistochemistry. Our data revealed that the ratio of trypsinogen to that of the protective pancreas-specific trypsin inhibitor was elevated upon cigarette smoke exposure. The expression of carbonic anhydrase and CFTR remained unaltered when inflammatory signs were not detected in histological examinations. On the other hand, when pancreatic inflammation was present, the levels of CFTR and carbonic anhydrase were increased, indicating ductal and/or centroacinar cell involvement. No changes in the expression of Muc1 and Muc4 mucins were observed. Our data show that cigarette smoke exposure leads to an increased vulnerability to pancreatic self-digestion. Moreover, the concomitant involvement of pancreatic ducts occurs only when focal pancreatic inflammation is present.

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

    Directory of Open Access Journals (Sweden)

    Luis Sarmiento

    2017-01-01

    Full Text Available 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.

  15. Identification of risk factors for pancreatic exocrine insufficiency after pancreaticoduodenectomy using a 13C-labeled mixed triglyceride breath test.

    Science.gov (United States)

    Hirono, Seiko; Murakami, Yoshiaki; Tani, Masaji; Kawai, Manabu; Okada, Ken-ichi; Uemura, Kenichiro; Sudo, Takeshi; Hashimoto, Yasushi; Nakagawa, Naoya; Kondo, Naru; Yamaue, Hiroki

    2015-02-01

    There are only a few reports concerning long-term exocrine function after pancreaticoduodenectomy (PD), although the number of long-term survivors has increased. We assessed pancreatic exocrine function after PD in 189 patients to identify risk factors for pancreatic exocrine insufficiency. We evaluated patients' exocrine function by using the (13)C-labeled mixed triglyceride breath test, a noninvasive test feasible in outpatient service units. The present study included 99 patients that underwent pancreaticojejunostomy (PJ) at Wakayama Medical University Hospital and 90 patients that underwent pancreaticogastrostomy (PG) at Hiroshima University Hospital, the standard reconstruction techniques during PD at the respective hospitals. We also analyzed long-term morphological changes of remnant pancreas by computed tomography (main pancreatic duct dilation and parenchymal atrophy), nutritional status, and endocrine function. Independent risk factors for exocrine insufficiency after PD include hard pancreas (P = 0.003, odds ratio; 3.157) and PG reconstruction (P = 0.040, odds ratio; 2.321). Breath test results correlated significantly with post-operative morphological changes, nutritional status, and endocrine function. Atrophic changes of the remnant pancreas in the PG group were more severe than those in the PJ group. Furthermore, for patients with a soft pancreas, postoperative body weight changes, prognostic nutritional index, serum total protein levels as well as exocrine test were worse in the PG group, compared with the PJ group. Our results showed that PJ reconstruction might be superior to PG during PD, from the viewpoint of long-term pancreatic exocrine function, although further prospective studies are needed.

  16. Behavioral experience induces zif268 expression in mature granule cells but suppresses its expression in immature granule cells

    Science.gov (United States)

    Huckleberry, Kylie A.; Kane, Gary A.; Mathis, Rita J.; Cook, Sarah G.; Clutton, Jonathan E.; Drew, Michael R.

    2015-01-01

    Thousands of neurons are born each day in the dentate gyrus (DG), but many of these cells die before reaching maturity. Both death and survival of adult-born neurons are regulated by neuronal activity in the DG. The immediate-early gene (IEG) zif268 appears to be an important mediator of these effects, as its expression can be induced by neural activity and knockout of zif268 impairs survival of adult-born neurons (Richardson et al., 1992; Veyrac et al., 2013). Despite the apparent importance of zif268 for adult neurogenesis, its behavior-induced expression has not been fully characterized in adult-born neurons. Here we characterize behavior-evoked expression of zif268 in mature and newborn dentate granule cells (DGCs). We first quantified zif268 expression in doublecortin-positive (DCX+) immature neurons and in the general granule cell population after brief exposure to a novel environment (NE). In the general granule cell population, zif268 expression peaked 1 h after NE exposure and returned to baseline by 8 h post-exposure. However, in the DCX+ cells, zif268 expression was suppressed relative to home cage for at least 8 h post-exposure. We next asked whether suppression of zif268 in DCX+ immature cells occurs in other behavioral paradigms that recruit the hippocampus. Exposure to Morris water maze (MWM) training, an enriched environment, or a NE caused approximately equal suppression of zif268 expression in DCX+ cells and approximately equal activation of zif268 expression among the general granule cell population. The same behavioral procedures activated zif268 expression in 6-week-old BrdU-labeled adult-born neurons, indicating that zif268 suppression is specific to immature neurons. Finally, we asked whether zif268 suppression varied as a function of age within the DCX+ population, which ranges in age from 0 to approximately 4 weeks. NE exposure had no significant effect on zif268 expression in 2- or 4-week-old BrdU-labeled neurons, but it significantly

  17. Application of tumbling melt granulation (TMG) method to prepare controlled-release fine granules.

    Science.gov (United States)

    Maejima, T; Kubo, M; Osawa, T; Nakajima, K; Kobayashi, M

    1998-03-01

    The tumbling melt granulation (TMG) method was applied to prepare controlled-release fine granules of diltiazem hydrochloride (DH). The entire process, from the preparation of the cores by the adherence of DH to the sucrose crystal to the subsequent coating of the controlled-release layer, was performed without using any solvent. A mixture of meltable material, talc, and ethylcellulose was used for the controlled-release layer and controlled-release fine granules approximately 400 microns in diameter were obtained with excellent producibility. The dissolution rate of DH from these fine granules was similar to that of a once-a-day dosage form obtained in the market; further, the dependency of the dissolution profile on pH of the media was less. Thus, it was concluded that this TMG method was very useful for preparing not only controlled-release beads of granule size (usually 500 to 1400 microns) but also fine granules.

  18. Expression of tryptophan 2,3-dioxygenase in mature granule cells of the adult mouse dentate gyrus

    Directory of Open Access Journals (Sweden)

    Ohira, Koji

    2010-09-01

    Full Text Available Abstract New granule cells are continuously generated in the dentate gyrus of the adult hippocampus. During granule cell maturation, the mechanisms that differentiate new cells not only describe the degree of cell differentiation, but also crucially regulate the progression of cell differentiation. Here, we describe a gene, tryptophan 2,3-dioxygenase (TDO, whose expression distinguishes stem cells from more differentiated cells among the granule cells of the adult mouse dentate gyrus. The use of markers for proliferation, neural progenitors, and immature and mature granule cells indicated that TDO was expressed in mature cells and in some immature cells. In mice heterozygous for the alpha-isoform of calcium/calmodulin-dependent protein kinase II, in which dentate gyrus granule cells fail to mature normally, TDO immunoreactivity was substantially downregulated in the dentate gyrus granule cells. Moreover, a 5-bromo-2'-deoxyuridine labeling experiment revealed that new neurons began to express TDO between 2 and 4 wk after the neurons were generated, when the axons and dendrites of the granule cells developed and synaptogenesis occurred. These findings indicate that TDO might be required at a late-stage of granule cell development, such as during axonal and dendritic growth, synaptogenesis and its maturation.

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    Extracellular adenosine triphosphate (ATP) regulates pancreatic duct function via P2Y and P2X receptors. It is well known that ATP is released from upstream pancreatic acinar cells. The ATP homeostasis in pancreatic ducts, which secrete bicarbonate-rich fluid, has not yet been examined. First, ou...... may be important in pancreas physiology and potentially in pancreas pathophysiology....... aim was to reveal whether pancreatic duct cells release ATP locally and whether they enzymatically modify extracellular nucleotides/sides. Second, we wished to explore which physiological and pathophysiological factors may be important in these processes. Using a human pancreatic duct cell line, Capan...

  20. Morphological study of the solar granulation. Pt. 2

    International Nuclear Information System (INIS)

    Kawaguchi, I.

    1980-01-01

    A time sequence of granulation images of 46 min long has allowed us to make a detailed study of the evolution of granules in an area of approximately 17 x 17 on the solar surface; It is found that the granules evolve by repeated fragmentation into smaller granules or merging with adjacent ones and that there are few granules which appear in the intergranular lanes as new granules (Table III). The statistical nature of granules is as follows: (1) A family of granules is defined as a group of granules produced from a single granule by fragmentation or merging. The lifetime is estimated for single granules and for families of granules. The lifetime shows a close correlation with the maximum size of a single granule or with that of the largest granule belonging to a family (Figures 5 and 7). (2) The smaller the size, the more probably a granule will disappear without further fragmentation or merging. The granule whose size is larger than 2 will certainly split or merge as the next evolutional step (Table IV.). (orig.)

  1. Snapin mediates insulin secretory granule docking, but not trans-SNARE complex formation

    Energy Technology Data Exchange (ETDEWEB)

    Somanath, Sangeeta [Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT (United Kingdom); Partridge, Christopher J. [Diabetes Research Laboratories, Oxford Centre for Diabetes, Endocrinology and Churchill Hospital, University of Oxford, Oxford, OX3 7LJ (United Kingdom); Marshall, Catriona [Blizard Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, E1 2AT (United Kingdom); Rowe, Tony [CSL Limited, 45 Poplar Road, Parkville, Victoria 3052 (Australia); Turner, Mark D., E-mail: mark.turner@ntu.ac.uk [Interdisciplinary Biomedical Research Centre, School of Science and Technology, Nottingham Trent University, Nottingham, NG11 8NS (United Kingdom)

    2016-04-29

    Secretory granule exocytosis is a tightly regulated process requiring granule targeting, tethering, priming, and membrane fusion. At the heart of this process is the SNARE complex, which drives fusion through a coiled-coil zippering effect mediated by the granule v-SNARE protein, VAMP2, and the plasma membrane t-SNAREs, SNAP-25 and syntaxin-1A. Here we demonstrate that in pancreatic β-cells the SNAP-25 accessory protein, snapin, C-terminal H2 domain binds SNAP-25 through its N-terminal Sn-1 domain. Interestingly whilst snapin binds SNAP-25, there is only modest binding of this complex with syntaxin-1A under resting conditions. Instead synataxin-1A appears to be recruited in response to secretory stimulation. These results indicate that snapin plays a role in tethering insulin granules to the plasma membrane through coiled coil interaction of snapin with SNAP-25, with full granule fusion competency only resulting after subsequent syntaxin-1A recruitment triggered by secretory stimulation. - Highlights: • Snapin mediates granule docking. • Snapin binds SNAP-25. • SNARE complex forms downstream.

  2. Snapin mediates insulin secretory granule docking, but not trans-SNARE complex formation

    International Nuclear Information System (INIS)

    Somanath, Sangeeta; Partridge, Christopher J.; Marshall, Catriona; Rowe, Tony; Turner, Mark D.

    2016-01-01

    Secretory granule exocytosis is a tightly regulated process requiring granule targeting, tethering, priming, and membrane fusion. At the heart of this process is the SNARE complex, which drives fusion through a coiled-coil zippering effect mediated by the granule v-SNARE protein, VAMP2, and the plasma membrane t-SNAREs, SNAP-25 and syntaxin-1A. Here we demonstrate that in pancreatic β-cells the SNAP-25 accessory protein, snapin, C-terminal H2 domain binds SNAP-25 through its N-terminal Sn-1 domain. Interestingly whilst snapin binds SNAP-25, there is only modest binding of this complex with syntaxin-1A under resting conditions. Instead synataxin-1A appears to be recruited in response to secretory stimulation. These results indicate that snapin plays a role in tethering insulin granules to the plasma membrane through coiled coil interaction of snapin with SNAP-25, with full granule fusion competency only resulting after subsequent syntaxin-1A recruitment triggered by secretory stimulation. - Highlights: • Snapin mediates granule docking. • Snapin binds SNAP-25. • SNARE complex forms downstream.

  3. Atrial natriuretic peptide (ANP)-granules: ultrastructure ...

    African Journals Online (AJOL)

    AJB SERVER

    2006-12-29

    Dec 29, 2006 ... morphometry and function. Eliane Florencio ... granules is greatest in the right atrium followed by the left atrium and left auricle and right auricle, in this order. ... family: Atrial natriuretic peptide (ANP), Urodilatin, Brain natriuretic ...

  4. Actinomyces associated with persistent vaginal granulation tissue.

    OpenAIRE

    Wai, Clifford Y; Nihira, Mikio A; Drewes, Peter G; Chang, Joe S; Siddiqui, Momin T; Hemsell, David L

    2005-01-01

    BACKGROUND: We report a case of symptomatic actinomycosis associated with vaginal suture erosion and granulation tissue refractory to conservative management, in an outpatient setting. CASE: Three months after total vaginal hysterectomy and uterosacral ligament vaginal vault suspension, a woman complained of painless, intermittent vaginal discharge and spotting. Despite cauterization of granulation tissue, vaginal spotting persisted for another month. On re-examination, braided polyester sutu...

  5. Mathematical model of melt flow channel granulator

    Directory of Open Access Journals (Sweden)

    A. A. Kiselev

    2016-01-01

    Full Text Available Granulation of carbohydrate-vitamin-mineral supplements based on molasses is performed at a high humidity (26 %, so for a stable operation of granulator it is necessary to reveal its melt flow pattern. To describe melt non-isothermal flow in the granulator a mathematical model with following initial equations: continuity equation, motion equation and rheological equation – was developed. The following assumptions were adopted: the melt flow in the granulator is a steady laminar flow; inertial and gravity forces can be ignored; melt is an incompressible fluid; velocity gradient in the flow direction is much smaller than in the transverse direction; the pressure gradient over the cross section of the channel is constant; the flow is hydrodynamically fully developed; effects impact on the channel inlet and outlet may be neglected. Due to the assumptions adopted, it can be considered that in this granulator only velocity components in the x-direction are significant and all the members of the equation with the components and their derivatives with respect to the coordinates y and z can be neglected. The resulting solutions were obtained: the equation for the mean velocity, the equation for determining the volume flow, the formula for calculating of mean time of the melt being in the granulator, the equation for determining the shear stress, the equation for determining the shear rate and the equation for determining the pressure loss. The results of calculations of the equations obtained are in complete agreement with the experimental data; deviation range is 16–19 %. The findings about the melt movement pattern in granulator allowed developing a methodology for calculating a rational design of the granulator molding unit.

  6. The effect of pancreatic polypeptide and peptide YY on pancreatic blood flow and pancreatic exocrine secretion in the anesthetized dog

    International Nuclear Information System (INIS)

    DeMar, A.R.; Lake, R.; Fink, A.S.

    1991-01-01

    Pancreatic polypeptide (PP) and peptide YY (PYY) are inhibitors of pancreatic exocrine secretion in vivo but not in vitro, which suggests intermediate mechanisms of action. To examine the role of pancreatic blood flow in these inhibitory effects, xenon-133 gas clearance was used to measure pancreatic blood flow while simultaneously measuring pancreatic exocrine secretion. PP or PYY (400 pmol/kg/h) was administered during the intermediate hour of a 3-h secretin (125 ng/kg/h)/cholecystokinin octapeptide (CCK-8) (50 ng/kg/h) infusion. Exocrine secretion and pancreatic blood flow during the PP or PYY hours were compared with that observed in the first and third hours of the secretin/CCK-8 infusion. PP and PYY significantly inhibited secretin/CCK-8-induced pancreatic exocrine secretion. In addition, PYY (but not PP) significantly reduced pancreatic blood flow during secretin/CCK-8 stimulation. Nevertheless, there was no correlation between pancreatic blood flow and bicarbonate or protein outputs. It is concluded that changes in pancreatic blood flow do not mediate the inhibitory effects of PP or PYY on the exocrine pancreas

  7. Population-Level Incidence and Predictors of Surgically Induced Diabetes and Exocrine Insufficiency after Partial Pancreatic Resection.

    Science.gov (United States)

    Elliott, Irmina A; Epelboym, Irene; Winner, Megan; Allendorf, John D; Haigh, Philip I

    2017-01-01

    Endocrine and exocrine insufficiency after partial pancreatectomy affect quality of life, cardiovascular health, and nutritional status. However, their incidence and predictors are unknown. To identify the incidence and predictors of new-onset diabetes and exocrine insufficiency after partial pancreatectomy. We retrospectively reviewed 1165 cases of partial pancreatectomy, performed from 1998 to 2010, from a large population-based database. Incidence of new onset diabetes and exocrine insufficiency RESULTS: Of 1165 patients undergoing partial pancreatectomy, 41.8% had preexisting diabetes. In the remaining 678 patients, at a median 3.6 months, diabetes developed in 274 (40.4%) and pancreatic insufficiency developed in 235 (34.7%) patients. Independent predictors of new-onset diabetes were higher Charlson Comorbidity Index (CCI; hazard ratio [HR] = 1.62 for CCI of 1, p = 0.02; HR = 1.95 for CCI ≥ 2, p pancreatitis (HR = 1.51, p = 0.03). There was no difference in diabetes after Whipple procedure vs distal pancreatic resections, or malignant vs benign pathologic findings. Independent predictors of exocrine insufficiency were female sex (HR = 1.32, p = 0.002) and higher CCI (HR = 1.85 for CCI of 1, p insufficiency (HR = 0.35, p endocrine and exocrine insufficiency were 40% and 35%, respectively. These data are critical for informing patients' and physicians' expectations.

  8. Delayed release pancrelipase for treatment of pancreatic exocrine insufficiency associated with chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Devi Mukkai Krishnamurty

    2009-07-01

    Full Text Available Devi Mukkai Krishnamurty,1 Atoosa Rabiee,2 Sanjay B Jagannath,1 Dana K Andersen2Johns Hopkins University School of Medicine; 1Department of Medicine; 2Department of Surgery, Johns Hopkins Hospital, Baltimore, MD, USA; 2Johns Hopkins University School of Medicine, Johns Hopkins Bayview Medical Center, Baltimore, MD, USAAbstract: Pancreatic enzyme supplements (PES are used in chronic pancreatitis (CP for correction of pancreatic exocrine insufficiency (PEI as well as pain and malnutrition. The use of porcine pancreatic enzymes for the correction of exocrine insufficiency is governed by the pathophysiology of the disease as well as pharmacologic properties of PES. Variability in bioequivalence of PES has been noted on in vitro and in vivo testing and has been attributed to the differences in enteric coating and the degree of micro-encapsulation. As a step towards standardizing pancreatic enzyme preparations, the Food and Drug Administration now requires the manufacturers of PES to obtain approval of marketed formulations by April 2010. In patients with treatment failure, apart from evaluating drug and dietary interactions and compliance, physicians should keep in mind that patients may benefit from switching to a different formulation. The choice of PES (enteric coated versus non-enteric coated and the need for acid suppression should be individualized. There is no current standard test for evaluating adequacy of therapy in CP patients and studies have shown that optimization of therapy based on symptoms may be inadequate. Goals of therapy based on overall patient presentation and specific laboratory tests rather than mere correction of steatorrhea are needed.Keywords: pancreatic exocrine insufficiency, chronic pancreatitis, pancreatic enzyme supplement

  9. Should we Investigate Gastroenterology Patients for Pancreatic Exocrine Insufficiency? A Dual Centre UK Study.

    Science.gov (United States)

    Campbell, Jennifer A; Sanders, David S; Francis, Katherine A; Kurien, Matthew; Lee, Sai; Taha, Hatim; Ramadas, Arvind; Joy, Diamond; Hopper, Andrew D

    2016-09-01

    Pancreatic exocrine insufficiency may be under recognised in gastroenterological practice. We aimed to identify the prevalence of pancreatic insufficiency in secondary care gastroenterology clinics and determine if co-morbidity or presenting symptoms could predict diagnosis. A secondary aim was to assess response to treatment. A dual centre retrospective analysis was conducted in secondary care gastroenterology clinics. Patients tested for pancreatic exocrine insufficiency with faecal elastase-1 (FEL-1) between 2009 and 2013 were identified in two centres. Demographics, indication and co-morbidities were recorded in addition to dose and response to pancreatic enzyme replacement therapy. Binary logistic regression was used to assess if symptoms or co-morbidities could predict pancreatic insufficiency. 1821 patients were tested, 13.1% had low FEL-1 (<200µg/g). This prevalence was sub-analysed with 5.4% having FEL-1 100-200µg/g (mild insufficiency) and 7.6% having faecal elastase readings <100µg/g. Low FEL-1 was most significantly associated with weight loss or steatorrhoea. Co-morbidity analysis showed that low levels were significantly associated with excess alcohol intake, diabetes mellitus or human immunodeficiency virus; 80.0% treated with enzyme supplements reported symptomatic benefit with no difference in response between high and low dose supplementation (p=0.761). Targeting the use of FEL-1 in individuals with specific symptoms and associated conditions can lead to improved recognition of pancreatic exocrine insufficiency in a significant proportion of secondary care patients. Intervening with lifestyle advice such as smoking cessation and minimising alcohol intake could improve outcomes. In addition, up to 80% of patients with low faecal elastase respond to supplementation.

  10. Pancreatic exocrine insufficiency, diabetes mellitus and serum nutritional markers after acute pancreatitis.

    Science.gov (United States)

    Vujasinovic, Miroslav; Tepes, Bojan; Makuc, Jana; Rudolf, Sasa; Zaletel, Jelka; Vidmar, Tjasa; Seruga, Maja; Birsa, Bostjan

    2014-12-28

    To investigate impairment and clinical significance of exocrine and endocrine pancreatic function in patients after acute pancreatitis (AP). 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. 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. 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.

  11. Summary and recommendations from the Australasian guidelines for the management of pancreatic exocrine insufficiency.

    Science.gov (United States)

    Smith, Ross C; Smith, Sarah F; Wilson, Jeremy; Pearce, Callum; Wray, Nick; Vo, Ruth; Chen, John; Ooi, Chee Y; Oliver, Mark; Katz, Tamarah; Turner, Richard; Nikfarjam, Mehrdad; Rayner, Christopher; Horowitz, Michael; Holtmann, Gerald; Talley, Nick; Windsor, John; Pirola, Ron; Neale, Rachel

    2016-01-01

    Because of increasing awareness of variations in the use of pancreatic exocrine replacement therapy, the Australasian Pancreatic Club decided it was timely to re-review the literature and create new Australasian guidelines for the management of pancreatic exocrine insufficiency (PEI). A working party of expert clinicians was convened and initially determined that by dividing the types of presentation into three categories for the likelihood of PEI (definite, possible and unlikely) they were able to consider the difficulties of diagnosing PEI and relate these to the value of treatment for each diagnostic category. Recent studies confirm that patients with chronic pancreatitis receive similar benefit from pancreatic exocrine replacement therapy (PERT) to that established in children with cystic fibrosis. Severe acute pancreatitis is frequently followed by PEI and PERT should be considered for these patients because of their nutritional requirements. Evidence is also becoming stronger for the benefits of PERT in patients with unresectable pancreatic cancer. However there is as yet no clear guide to help identify those patients in the 'unlikely' PEI group who would benefit from PERT. For example, patients with coeliac disease, diabetes mellitus, irritable bowel syndrome and weight loss in the elderly may occasionally be given a trial of PERT, but determining its effectiveness will be difficult. The starting dose of PERT should be from 25,000-40,000 IU lipase taken with food. This may need to be titrated up and there may be a need for proton pump inhibitors in some patients to improve efficacy. Copyright © 2016 IAP and EPC. Published by Elsevier India Pvt Ltd. All rights reserved.

  12. Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms.

    Science.gov (United States)

    Lowery, Maeve A; Wong, Winston; Jordan, Emmet J; Lee, Jonathan W; Kemel, Yelena; Vijai, Joseph; Mandelker, Diana; Zehir, Ahmet; Capanu, Marinela; Salo-Mullen, Erin; Arnold, Angela G; Yu, Kenneth H; Varghese, Anna M; Kelsen, David P; Brenner, Robin; Kaufmann, Erica; Ravichandran, Vignesh; Mukherjee, Semanti; Berger, Michael F; Hyman, David M; Klimstra, David S; Abou-Alfa, Ghassan K; Tjan, Catherine; Covington, Christina; Maynard, Hannah; Allen, Peter J; Askan, Gokce; Leach, Steven D; Iacobuzio-Donahue, Christine A; Robson, Mark E; Offit, Kenneth; Stadler, Zsofia K; O'Reilly, Eileen M

    2018-02-28

    Identification of pathogenic germline alterations (PGAs) has important clinical and therapeutic implications in pancreas cancer. We performed comprehensive germline testing (GT) in an unselected prospective cohort of patients with exocrine pancreatic neoplasms with genotype and phenotype association to facilitate identification of prognostic and/or predictive biomarkers and examine potential therapeutic implications. Six hundred fifteen unselected patients with exocrine pancreatic neoplasms were prospectively consented for somatic tumor and matched sample profiling for 410-468 genes. GT for PGAs in 76 genes associated with cancer susceptibility was performed in an "identified" manner in 356 (57.9%) patients and in an "anonymized" manner in 259 (42.1%) patients, using an institutional review board-approved protocol. Detailed clinical and pathological features, response to platinum, and overall survival (OS) were collected for the identified cohort. OS was analyzed with Kaplan-Meier curves. PGAs were present in 122 (19.8%) of 615 patients involving 24 different genes, including BRCA1/2, ATM, PALB2, and multiple additional genes associated with the DNA damage response pathway. Of 122 patients with germline alterations, 41.8% did not meet current guidelines for GT. The difference in median OS was not statistically significant between patients with and without PGA (50.8 months, 95% confidence interval = 34.5 to not reached, two-sided P = .94). Loss of heterozygosity was found in 60.0% of BRCA1/2. PGAs frequently occur in pancreas exocrine neoplasms and involve multiple genes beyond those previously associated with hereditary pancreatic cancer. These PGAs are therapeutically actionable in about 5% to 10% of patients. These data support routinely offering GT in all pancreatic ductal adenocarcimona patients with a broad panel of known hereditary cancer predisposition genes.

  13. New advances in cell physiology and pathophysiology of the exocrine pancreas.

    Science.gov (United States)

    Mössner, Joachim

    2010-01-01

    This review provides some aspects on the physiology of stimulation and inhibition of pancreatic digestive enzyme secretion and the pathophysiology of pancreatic acinar cell function leading to pancreatitis. Cholecystokinin (CCK) stimulates both directly via CCK-A receptors on acinar cells and indirectly via CCK-B receptors on nerves, followed by acetylcholine release, pancreatic enzyme secretion. It is still not known whether CCK-A receptors exist in human acinar cells, in contrast to acinar cells of rodents where CCK-A receptors have been well described. CCK has numerous actions both in the periphery and in the central nervous systems. CCK inhibits gastric motility and regulates satiety. Another major function of CCK is stimulation of gallbladder contraction. This function enables that bile acids act simultaneously with pancreatic lipolytic enzymes. Secretin is a major stimulator of bicarbonate secretion. Trypsinogen is activated by the gut mucosal enzyme enterokinase. The other pancreatic proenzymes are activated by trypsin. Termination of enzyme secretion may be regulated by negative feedback mechanisms via destruction of CCK-releasing peptides by trypsin. Furthermore, the ileum may act as a brake by release of inhibitory hormones such as PYY and somatostatin. In the pathophysiology of acute pancreatitis, fusion of zymogen granules with lysosomes leading to intracellular activation of trypsinogen is regarded as an initiation step. This activation of trypsinogen may be caused by the lysosomal enzyme cathepsin B. However, autoactivation of trypsinogen itself may be a possibility in pathogenesis. Autoactivation is enhanced in certain mutations of trypsinogen. Furthermore, an imbalance of protease inhibitors and active proteases may be involved. The role of pancreatic lipolytic enzymes, the role of bicarbonate secretion, and toxic Ca(2+) signals by excessive liberation from the endoplasmic reticulum have to be discussed in the pathogenesis of acute pancreatitis

  14. MicroRNAs Promote Granule Cell Expansion in the Cerebellum Through Gli2.

    Science.gov (United States)

    Constantin, Lena; Wainwright, Brandon J

    2015-12-01

    MicroRNAs (miRNAs) are important regulators of cerebellar function and homeostasis. Their deregulation results in cerebellar neuronal degeneration and spinocerebellar ataxia type 1 and contributes to medulloblastoma. Canonical miRNA processing involves Dicer, which cleaves precursor miRNAs into mature double-stranded RNA duplexes. In order to address the role of miRNAs in cerebellar granule cell precursor development, loxP-flanked exons of Dicer1 were conditionally inactivated using the granule cell precursor-specific Atoh1-Cre recombinase. A reduction of 87% in Dicer1 transcript was achieved in this conditional Dicer knockdown model. Although knockdown resulted in normal survival, mice had disruptions to the cortical layering of the anterior cerebellum, which resulted from the premature differentiation of granule cell precursors in this region during neonatal development. This defect manifested as a thinner external granular layer with ectopic mature granule cells, and a depleted internal granular layer. We found that expression of the activator components of the Hedgehog-Patched pathway, the Gli family of transcription factors, was perturbed in conditional Dicer knockdown mice. We propose that loss of Gli2 mRNA mediated the anterior-restricted defect in conditional Dicer knockdown mice and, as proof of principle, were able to show that miR-106b positively regulated Gli2 mRNA expression. These findings confirm the importance of miRNAs as positive mediators of Hedgehog-Patched signalling during granule cell precursor development.

  15. Coevolved crypts and exocrine glands support mutualistic bacteria in fungus-growing ants

    DEFF Research Database (Denmark)

    Currie, Cameron R; Poulsen, Michael; Mendenhall, John

    2006-01-01

    Attine ants engage in a quadripartite symbiosis with fungi they cultivate for food, specialized garden parasites, and parasite-inhibiting bacteria. Molecular phylogenetic evidence supports an ancient host-pathogen association between the ant-cultivar mutualism and the garden parasite. Here we show...... that ants rear the antibiotic-producing bacteria in elaborate cuticular crypts, supported by unique exocrine glands, and that these structures have been highly modified across the ants' evolutionary history. This specialized structural evolution, together with the absence of these bacteria and modifications...

  16. The role of nitric oxide in the physiology and pathophysiology of the exocrine pancreas.

    Science.gov (United States)

    Hegyi, Péter; Rakonczay, Zoltán

    2011-11-15

    Nitric oxide (NO), a ubiquitous gaseous signaling molecule, contributes to both pancreatic physiology and pathophysiology. The present review provides a general overview of NO synthesis, signaling, and function. Further, it specifically discusses NO metabolism and its effects in the exocrine pancreas and focuses on the role of NO in the pathogenesis of acute pancreatitis and pancreatic ischemia/reperfusion injury. Unfortunately, the role of NO in pancreatic physiology and pathophysiology remains controversial in numerous areas. Many questions regarding the messenger molecule still remain unanswered. Probably the least is known about the downstream targets of NO, which need to be identified, especially at the molecular level.

  17. Romanian guidelines on the diagnosis and treatment of exocrine pancreatic insufficiency

    DEFF Research Database (Denmark)

    Gheorghe, Cristian; Seicean, Andrada; Saftoiu, Adrian

    2015-01-01

    In assessing exocrine pancreatic insufficiency (EPI), its diverse etiologies and the heterogeneous population affected should be considered. Diagnosing this condition remains a challenge in clinical practice especially for mild-to-moderate EPI, with the support of the time-consuming breath test o...... indicated in patients with celiac disease, who have chronic diarrhea (in spite of gluten-free diet), and in patients with cystic fibrosis with proven EPI....... on an individual's weight and clinical symptoms. The main indication for PERT is chronic pancreatitis, in patients who have clinically relevant steatorrhea, abnormal pancreatic function test or abnormal function tests associated with symptoms of malabsorption such as weight loss or meteorism. While enzyme...

  18. Granule size control and targeting in pulsed spray fluid bed granulation.

    Science.gov (United States)

    Ehlers, Henrik; Liu, Anchang; Räikkönen, Heikki; Hatara, Juha; Antikainen, Osmo; Airaksinen, Sari; Heinämäki, Jyrki; Lou, Honxiang; Yliruusi, Jouko

    2009-07-30

    The primary aim of the study was to investigate the effects of pulsed liquid feed on granule size. The secondary aim was to increase knowledge of this technique in granule size targeting. Pulsed liquid feed refers to the pump changing between on- and off-positions in sequences, called duty cycles. One duty cycle consists of one on- and off-period. The study was performed with a laboratory-scale top-spray fluid bed granulator with duty cycle length and atomization pressure as studied variables. The liquid feed rate, amount and inlet air temperature were constant. The granules were small, indicating that the powder has only undergone ordered mixing, nucleation and early growth. The effect of atomizing pressure on granule size depends on inlet air relative humidity, with premature binder evaporation as a reason. The duty cycle length was of critical importance to the end product attributes, by defining the extent of intermittent drying and rewetting. By varying only the duty cycle length, it was possible to control granule nucleation and growth, with a wider granule size target range in increased relative humidity. The present study confirms that pulsed liquid feed in fluid bed granulation is a useful tool in end product particle size targeting.

  19. Study of light scattering by a granulated coated sphere - a model of granulated blood cells

    NARCIS (Netherlands)

    Yurkin, M.A.; de Kanter, D.; Hoekstra, A.G.

    2008-01-01

    We performed extensive simulations of light scattering by granulated coated sphere model using the discrete dipole approximation and varying model parameters in the ranges of sizes and refractive indices of granulated blood cells. We compared these results with predictions of Maxwell-Garnett

  20. Investigation of Physicochemical Drug Properties to Prepare Fine Globular Granules Composed of Only Drug Substance in Fluidized Bed Rotor Granulation.

    Science.gov (United States)

    Mise, Ryohei; Iwao, Yasunori; Kimura, Shin-Ichiro; Osugi, Yukiko; Noguchi, Shuji; Itai, Shigeru

    2015-01-01

    The effect of some drug properties (wettability and particle size distribution) on granule properties (mean particle size, particle size distribution, sphericity, and granule strength) were investigated in a high (>97%) drug-loading formulation using fluidized bed rotor granulation. Three drugs: acetaminophen (APAP); ibuprofen (IBU); and ethenzamide (ETZ) were used as model drugs based on their differences in wettability and particle size distribution. Granules with mean particle sizes of 100-200 µm and a narrow particle size distribution (PSD) could be prepared regardless of the drug used. IBU and ETZ granules showed a higher sphericity than APAP granules, while APAP and ETZ granules exhibited higher granule strength than IBU. The relationship between drug and granule properties suggested that the wettability and the PSD of the drugs were critical parameters affecting sphericity and granule strength, respectively. Furthermore, the dissolution profiles of granules prepared with poorly water-soluble drugs (IBU and ETZ) showed a rapid release (80% release in 20 min) because of the improved wettability with granulation. The present study demonstrated for the first time that fluidized bed rotor granulation can prepare high drug-loaded (>97%) globular granules with a mean particle size of less than 200 µm and the relationship between physicochemical drug properties and the properties of the granules obtained could be readily determined, indicating the potential for further application of this methodology to various drugs.

  1. The pancreatic zymogen granule membrane protein, GP2, binds Escherichia coli type 1 Fimbriae

    Directory of Open Access Journals (Sweden)

    Lowe Anson W

    2009-07-01

    Full Text Available Abstract Background GP2 is the major membrane protein present in the pancreatic zymogen granule, and is cleaved and released into the pancreatic duct along with exocrine secretions. The function of GP2 is unknown. GP2's amino acid sequence is most similar to that of uromodulin, which is secreted by the kidney. Recent studies have demonstrated uromodulin binding to bacterial Type 1 fimbria. The fimbriae serve as adhesins to host receptors. The present study examines whether GP2 also shares similar binding properties to bacteria with Type 1 fimbria. Commensal and pathogenic bacteria, including E. coli and Salmonella, express type 1 fimbria. Methods An in vitro binding assay was used to assay the binding of recombinant GP2 to defined strains of E. coli that differ in their expression of Type 1 fimbria or its subunit protein, FimH. Studies were also performed to determine whether GP2 binding is dependent on the presence of mannose residues, which is a known determinant for FimH binding. Results GP2 binds E. coli that express Type 1 fimbria. Binding is dependent on GP2 glycosylation, and specifically the presence of mannose residues. Conclusion GP2 binds to Type 1 fimbria, a bacterial adhesin that is commonly expressed by members of the Enterobacteriacae family.

  2. A prospective assessment of the natural course of the exocrine pancreatic function in patients with a pancreatic head tumor.

    Science.gov (United States)

    Sikkens, Edmée C M; Cahen, Djuna L; de Wit, Jill; Looman, Caspar W N; van Eijck, Casper; Bruno, Marco J

    2014-01-01

    In cancer of the pancreatic head region, exocrine insufficiency is a well-known complication, leading to steatorrhea, weight loss, and malnutrition. Its presence is frequently overlooked, however, because the primary attention is focused on cancer treatment. To date, the risk of developing exocrine insufficiency is unspecified. Therefore, we assessed this function in patients with tumors of the pancreatic head, distal common bile duct, or ampulla of Vater. Between March 2010 and August 2012, we prospectively included patients diagnosed with cancer of the pancreatic head region at our tertiary center. To preclude the effect of a resection, we excluded operated patients. Each month, the exocrine function was determined with a fecal elastase test. Furthermore, endocrine function, steatorrhea-related symptoms, and body weight were evaluated. Patients were followed for 6 months, or until death. Thirty-two patients were included. The tumor was located in the pancreas in 75%, in the bile duct in 16%, and in the ampullary region in 9%, with a median size of 2.5 cm. At diagnosis, the prevalence of exocrine insufficiency was 66%, which increased to 92% after a median follow-up of 2 months (interquartile range, 1 to 4 mo). Most patients with cancer of the pancreatic head region were already exocrine insufficient at diagnosis, and within several months, this function was impaired in almost all cases. Given this high prevalence, physicians should be focused on diagnosing and treating exocrine insufficiency, to optimize the nutritional status and physical condition, especially for those patients undergoing palliative chemotherapy and/or radiotherapy.

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

    OpenAIRE

    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 ...

  4. Secretion of a recombinant protein without a signal peptide by the exocrine glands of transgenic rabbits.

    Directory of Open Access Journals (Sweden)

    Andrea Kerekes

    Full Text Available Transgenic rabbits carrying mammary gland specific gene constructs are extensively used for excreting recombinant proteins into the milk. Here, we report refined phenotyping of previously generated Venus transposon-carrying transgenic rabbits with particular emphasis on the secretion of the reporter protein by exocrine glands, such as mammary, salivary, tear and seminal glands. The Sleeping Beauty (SB transposon transgenic construct contains the Venus fluorophore cDNA, but without a signal peptide for the secretory pathway, driven by the ubiquitous CAGGS (CAG promoter. Despite the absence of a signal peptide, the fluorophore protein was readily detected in milk, tear, saliva and seminal fluids. The expression pattern was verified by Western blot analysis. Mammary gland epithelial cells of SB-CAG-Venus transgenic lactating does also showed Venus-specific expression by tissue histology and fluorescence microscopy. In summary, the SB-CAG-Venus transgenic rabbits secrete the recombinant protein by different glands. This finding has relevance not only for the understanding of the biological function of exocrine glands, but also for the design of constructs for expression of recombinant proteins in dairy animals.

  5. Are there still roles for exocrine bladder drainage and portal venous drainage for pancreatic allografts?

    Science.gov (United States)

    Young, Carlton J

    2009-02-01

    Controversy remains regarding the best methodology of handling exocrine pancreatic fluid and pancreatic venous effluent. Bladder drainage has given way to enteric drainage. However, is there an instance in which bladder drainage is preferable? Also, hyperinsulinemia, as a result of systemic venous drainage (SVD), is claimed to be proatherosclerotic, whereas portal venous drainage (PVD) is more physiologic and less atherosclerotic. Bladder drainage remains a viable method of exocrine pancreas drainage, but evidence is sparse that measuring urinary amylase has a substantial benefit in the early detection of acute rejection in all types of pancreas transplants. Currently, there is no incontrovertible evidence that systemic hyperinsulinemia is proatherosclerotic, whereas recent metabolic studies on SVD and PVD showed that there was no benefit to PVD. Given the advent of newer immunosuppressive agents and overall lower acute rejection rates, the perceived benefit of bladder drainage as a means to measure urinary amylase as an early marker of rejection has not been substantiated. However, there may be a selective role for bladder drainage in 'high risk' pancreases. Also, without a clear-cut metabolic benefit to PVD over SVD, it remains the surgeon's choice as to which method to use.

  6. Acute effects of whole body gamma irradiation on exocrine pancreatic secretion in the pig

    International Nuclear Information System (INIS)

    Monti, P.; Scanff, P.; Joubert, C.; Vergnet, M.; Grison, S.; Griffiths, N.

    2004-01-01

    Reports on radiation damage to the pancreas deal essentially with long-term morphological changes with few data on pancreatic exocrine function. The aim of this work was to study the acute effects of whole body irradiation on volume and enzyme activities in the pancreatic juice. A whole body gamma irradiation (6 Gy) was investigated in pigs with continuous sampling of pancreatic juice before and after exposure via an indwelling catheter in the pancreatic duct. For each sample collected, total protein concentration and enzyme activities of trypsin, chymotrypsin, elastase, lipase and amylase were determined. Pancreatic juice volume was monitored during all periods of collection. The volume of pancreatic juice secreted daily decreased one day after irradiation and remained lower than the control values over the experimental period. Total proteins secreted in the pancreatic juice and total activities of pancreatic enzymes were reduced similarly. On the other hand, only specific activities of elastase and lipase were affected by irradiation. Whole body gamma irradiation resulted in a rapid and marked decrease of exocrine pancreatic secretion, in terms of volume as well as secreted enzymes. This may contribute in part to the intestinal manifestations of the acute and/or late radiation syndrome. (author)

  7. Exocrine pancreatic insufficiency in a yellow-naped Amazon (Amazona ochrocephala) with pancreatic adenocarcinoma.

    Science.gov (United States)

    Ritchey, J W; Degernes, L A; Brown, T T

    1997-01-01

    This report describes exocrine pancreatic insufficiency in a yellow-naped Amazon (Amazona ochrocephala) with complete effacement of the pancreas by a pancreatic adenocarcinoma. The bird presented with a 3-month history of weight loss and voluminous, foul-smelling droppings. Clinically, routine hematologic findings were normal and fecal tests were performed to evaluate exocrine pancreatic function. The fecal function tests were positive for neutral and split fats and negative for trypsin. Oral administration of corn oil did not result in elevation of blood triglyceride levels. Two days later, the triglyceride tolerance test was repeated using corn oil mixed with pancreatic enzymes. This time, there was a 70% elevation of blood triglyceride levels. Because of a poor prognosis, the bird was euthanatized. At necropsy, the pancreas was diffusely enlarged, white, nodular, and firm. The liver contained multiple, 1-2-mm-diameter, randomly located, tan nodules. Microscopically, the pancreas was effaced by numerous lobules of neoplastic ductular structures surrounded by abundant fibrous connective tissue. In the liver, the hepatic parenchyma was replaced by multiple, well-demarcated, nonencapsulated foci of neoplastic tissue similar to that in the pancreas.

  8. The clypeal gland: a new exocrine gland in termite imagoes (Isoptera: Serritermitidae, Rhinotermitidae, Termitidae).

    Science.gov (United States)

    Křížková, Barbora; Bourguignon, Thomas; Vytisková, Blahoslava; Sobotník, Jan

    2014-11-01

    Social insects possess a rich set of exocrine organs producing diverse pheromones and defensive compounds. This is especially true for termite imagoes, which are equipped with several glands producing, among others, sex pheromones and defensive compounds protecting imagoes during the dispersal flight and colony foundation. Here, we describe the clypeal gland, a new termite exocrine organ occurring in the labro-clypeal region of imagoes of most Rhinotermitidae, Serritermitidae and Termitidae species. The clypeal gland of Coptotermes testaceus consists of class 1 (modified epidermal cell) and class 3 (bicellular gland unit) secretory cells. Ultrastructural features suggest that the gland secretes volatile compounds and proteins, probably after starting the reproduction. One peculiar feature of the gland is the presence of multiple secretory canals in a single canal cell, a feature never observed before in other insect glands. Although the function of the gland remains unknown, we hypothesize that it could produce secretion signalling the presence of functional reproductives or their need to be fed. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. p38 Mitogen-activated protein kinase modulates exocrine secretion in rabbit lacrimal gland.

    Science.gov (United States)

    Carlsson, Stina K; Gierow, J Peter

    2012-03-01

    The lacrimal gland (LG) is an exocrine gland important for secretion of the tear film. The kinase p38 has important signal transduction functions, e.g. in gene transcription, but has previously not been known to modulate exocrine secretion. The aim of the current study was to investigate the role of p38 in carbachol (Cch)-induced LG secretion in LG acinar cells in vitro. Western blotting was used to determine the phosphorylation status of p38 and p42/44 and determine expression of p38 isoforms. To determine the effect of p38 inhibition on LG secretion, PD 169316, a general p38 inhibitor, and SB 239063, an inhibitor of p38α and β, were added to the cells prior to secretion measurements. The results revealed activation of p38 mediated by Cch stimulation and inhibition of Cch-induced secretion as a result of p38 inhibition. The inhibition was observed with PD 169316 isoforms, but not with SB 239063. The p38δ isoform was shown to have robust expression both by Western blotting of acinar cells and immunofluorescence of the whole gland. In conclusion, p38 activation mediates secretion in cholinergic stimulation of rabbit LG cells.

  10. Evaluation of the marker technique for measurement of exocrine pancreatic secretion rate

    International Nuclear Information System (INIS)

    Rune, S.J.; Worning, H.

    1985-01-01

    A secretin-cholecystokinin test was performed in 103 patients, representing both normal and reduced exocrine pancreatic function. The duodenum was intubated with a triple-lumen tube. The gastric and duodenal contents were aspirated separately and sampled in 10-min. periods. An inert, water-soluble marker ( 58 Co-vitamin B 12 dissolved in isotonic saline) was infused at a constant rate into the duodenum. Exocrine panreatic secretion was stimulated by continuous intravenous infusion of secretin for 60 min. and a combination of secretin and cholecystokinin for another 60 min. The total recovery of the infused marker was 80%. The concentration of marker in the aspriate did not vary significantly between consecutive 10-min. periods during the last 20 min. of the secretin stimulation period, or during the last 50 min. of the combined secretin-cholecystokinin stimulation period, indicating a steady secretion rate into the duodenum. By means of the marker, concentrations in the aspirate, the duodenal volumes were calculated and found to vary significantly less than the aspirated volumes. This finding demonstrates that the duodenal volume calculated from the recovery of an inert marker, is a closer estimate of the true volume than that obtained by the usual apsiration technique without a volume indicator

  11. Secretion of a recombinant protein without a signal peptide by the exocrine glands of transgenic rabbits.

    Science.gov (United States)

    Kerekes, Andrea; Hoffmann, Orsolya Ivett; Iski, Gergely; Lipták, Nándor; Gócza, Elen; Kues, Wilfried A; Bősze, Zsuzsanna; Hiripi, László

    2017-01-01

    Transgenic rabbits carrying mammary gland specific gene constructs are extensively used for excreting recombinant proteins into the milk. Here, we report refined phenotyping of previously generated Venus transposon-carrying transgenic rabbits with particular emphasis on the secretion of the reporter protein by exocrine glands, such as mammary, salivary, tear and seminal glands. The Sleeping Beauty (SB) transposon transgenic construct contains the Venus fluorophore cDNA, but without a signal peptide for the secretory pathway, driven by the ubiquitous CAGGS (CAG) promoter. Despite the absence of a signal peptide, the fluorophore protein was readily detected in milk, tear, saliva and seminal fluids. The expression pattern was verified by Western blot analysis. Mammary gland epithelial cells of SB-CAG-Venus transgenic lactating does also showed Venus-specific expression by tissue histology and fluorescence microscopy. In summary, the SB-CAG-Venus transgenic rabbits secrete the recombinant protein by different glands. This finding has relevance not only for the understanding of the biological function of exocrine glands, but also for the design of constructs for expression of recombinant proteins in dairy animals.

  12. A Survey of Sludge Granulation Theories Under Anaerobic Conditions

    Directory of Open Access Journals (Sweden)

    Jalal Shayegan

    2011-01-01

    Full Text Available This paper surveys the different theories developed on anaerobic sludge granulation. The theories are generally categorized as physical, microbial, and thermodynamic approaches. In the physical approach to the granulation process, granulation is described by such physical conditions of the reactor as upflow velocity of gas and liquid streams, suspended solids in the effluent flow, and excess sludge removal. Microbial theories are based on the properties of specific organisms and on granule properties (granule structure and its microbiology. The thermodynamic approach studies such factors as hydrophobia, electrophoretic mobility, effective energy in granule adhesion process, and effect of proton transferring activities on bacterial membrane surfaces.

  13. Study of granulated nickel alloy superplasticity

    International Nuclear Information System (INIS)

    Anoshkin, N.F.; Fatkullin, O.Kh.; Ermanok, M.Z.; Sharshagin, N.A.

    1982-01-01

    Peculiarities of the structure and properties of compact material obtained from granules of the EhI 698 and ZhS6U alloys in the form of pressed rods are investigated. It is shown, that granule metallurgy is the most rational technology method, ensuring the receipt of stable fine-grained structure in the initial blank. After appropriate thermal treatment the products obtained by the method of granule metallyrgy have more high strength characteristics at the room temperature and heat resistance, than typical for the products produced by traditional technology. Creation of specialized vertical presses providing low rates of deformation as well as their equipment by vacuum mechanizms which permit to use a tool from molybdenum alloys is necessary for successful introduction into production of the processes of plastic metal working under conditions of superplasticity

  14. Antimicrobial-Coated Granules for Disinfecting Water

    Science.gov (United States)

    Akse, James R.; Holtsnider, John T.; Kliestik, Helen

    2011-01-01

    Methods of preparing antimicrobialcoated granules for disinfecting flowing potable water have been developed. Like the methods reported in the immediately preceding article, these methods involve chemical preparation of substrate surfaces (in this case, the surfaces of granules) to enable attachment of antimicrobial molecules to the surfaces via covalent bonds. A variety of granular materials have been coated with a variety of antimicrobial agents that include antibiotics, bacteriocins, enzymes, bactericides, and fungicides. When employed in packed beds in flowing water, these antimicrobial-coated granules have been proven effective against gram-positive bacteria, gram-negative bacteria, fungi, and viruses. Composite beds, consisting of multiple layers containing different granular antimicrobial media, have proven particularly effective against a broad spectrum of microorganisms. These media have also proven effective in enhancing or potentiating the biocidal effects of in-line iodinated resins and of very low levels of dissolved elemental iodine.

  15. Chromospheric impact of an exploding solar granule

    Science.gov (United States)

    Fischer, C. E.; Bello González, N.; Rezaei, R.

    2017-06-01

    Context. Observations of multi-wavelength and therefore height-dependent information following events throughout the solar atmosphere and unambiguously assigning a relation between these rapidly evolving layers are rare and difficult to obtain. Yet, they are crucial for our understanding of the physical processes that couple the different regimes in the solar atmosphere. Aims: We characterize the exploding granule event with simultaneous observations of Hinode spectroplarimetric data in the solar photosphere and Hinode broadband Ca II H images combined with Interface Region Imaging Spectrograph (IRIS) slit spectra. We follow the evolution of an exploding granule and its connectivity throughout the atmosphere and analyze the dynamics of a magnetic element that has been affected by the abnormal granule. Methods: In addition to magnetic flux maps we use a local correlation tracking method to infer the horizontal velocity flows in the photosphere and apply a wavelet analysis on several IRIS chromospheric emission features such as Mg II k2v and Mg II k3 to detect oscillatory phenomena indicating wave propagation. Results: During the vigorous expansion of the abnormal granule we detect radially outward horizontal flows, causing, together with the horizontal flows from the surrounding granules, the magnetic elements in the bordering intergranular lanes to be squeezed and elongated. In reaction to the squeezing, we detect a chromospheric intensity and velocity oscillation pulse which we identify as an upward traveling hot shock front propagating clearly through the IRIS spectral line diagnostics of Mg II h&k. Conclusions: Exploding granules can trigger upward-propagating shock fronts that dissipate in the chromosphere. Movies associated to Figs. A.1 and A.2 are available in electronic form at http://www.aanda.org

  16. Lemongrass Oil Granules AS Aedes Aegypti Larvicide

    OpenAIRE

    Mulyani, Sri

    2014-01-01

    One way to prevent the spread of Haemorrhage Dengue Fever is the use of abate. The use of abate as larvicides often complained causing an unpleasant smell, and can cause resistance. Lemongrass oil is reported to have activity as larvicides, and this study aims to make granules of lemongrass oil preparation, as well as determining the value of LC50, LC90 against larvae of Ae. aegypti instar III. The granules of lemongrass oil preparation are made with lactose filler and binder CMC-Na. Larvicid...

  17. Method of producing granulated ceramic nuclear fuels

    International Nuclear Information System (INIS)

    Wilkinson, W.L.

    1976-01-01

    For the production of granulated ceramic nuclear fuels with a grain size spectrum as narrow as possible it is proposed to suspend the nuclear fuel powder in a non-aqueous solvent with small content of hydrogen (e.g. chloridized hydrocarbons) while adding a binding agent and then dry it by means of rays. As binding agent polybutyl methane acrylate in dibutyl phthalate is proposed. The method is described by the example of UO 2 -powder in trichloroethylene. The dry granulated material is produced in one working step. (UWI) [de

  18. Arachnoid granulation affected by subarachnoid hemorrhage

    Directory of Open Access Journals (Sweden)

    R.P. Chopard

    1993-11-01

    Full Text Available The purpose of this study was to investigate using light microscopy the fibro-cellular components of arachnoid granulations affected by mild and severe subarachnoid hemorrage. The erythrocytes were in the channels delimitated by collagenous and elastic bundles and arachnoid cells, showing their tortuous and intercommunicating row from the pedicle to the fibrous capsule. The core portion of the pedicle and the center represented a principal route to the bulk outflow of cerebrospinal fluid and erythrocytes. In the severe hemorrhage, the fibrocellular components are desorganized, increasing the extracellular channels. We could see arachnoid granulations without erythrocytes, which cells showed big round nucleous suggesting their transformation into phagocytic cells.

  19. Creep of granulated loose-fill insulation

    DEFF Research Database (Denmark)

    Rasmussen, Torben Valdbjørn

    This report presents a proposal for a standardised method for creep tests and the necessary theoretical framework that can be used to describe creep of a granulated loose-fill material. Furthermore results from a round robin test are shown. The round robin test was carried out in collaboration...... with SP-Building Physics in Sweden and VTT Building Technology in Finland. For the round robin test a cellulosic fibre insulation material was used. The proposed standardised method for creep tests and theories are limited to cases when the granulated loose-fill material is exposed to a constant...

  20. Molecular composition of IMP1 ribonucleoprotein granules

    DEFF Research Database (Denmark)

    Jønson, Lars; Vikesaa, Jonas; Krogh, Anders

    2007-01-01

    Localized mRNAs are transported to sites of local protein synthesis in large ribonucleoprotein (RNP) granules, but their molecular composition is incompletely understood. Insulin-like growth factor II mRNA-binding protein (IMP) zip code-binding proteins participate in mRNA localization, and in mo......Localized mRNAs are transported to sites of local protein synthesis in large ribonucleoprotein (RNP) granules, but their molecular composition is incompletely understood. Insulin-like growth factor II mRNA-binding protein (IMP) zip code-binding proteins participate in mRNA localization...

  1. Accumulation of PHA granules in Cupriavidus necator as seen by confocal fluorescence microscopy.

    Science.gov (United States)

    Mravec, Filip; Obruca, Stanislav; Krzyzanek, Vladislav; Sedlacek, Petr; Hrubanova, Kamila; Samek, Ota; Kucera, Dan; Benesova, Pavla; Nebesarova, Jana

    2016-05-01

    Many bacteria are capable of accumulating intracellular granules of polyhydroxyalkanoates (PHA). In this work, we developed confocal microscopy analysis of bacterial cells to study changes in the diameters of cells as well as PHA granules during growth and PHA accumulation in the bacterium Cupriavidus necator H16 (formerly Ralstonia eutropha). The cell envelope was stained by DiD(®) fluorescent probe and PHA granules by Nile Red. Signals from both probes were separated based on their spectral and fluorescence life-time properties. During growth and PHA accumulation, bacterial cells increased their length but the width of the cells remained constant. The volume fraction of PHA granules in cells increased during PHA accumulation, nevertheless, its value did not exceed 40 vol. % regardless of the PHA weight content. It seems that bacterial cultures lengthen the cells in order to control the PHA volume portion. However, since similar changes in cell length were also observed in a PHA non-accumulating mutant, it seems that there is no direct control mechanism, which regulates the prolongation of the cells with respect to PHA granules volume. It is more likely that PHA biosynthesis and the length of cells are influenced by the same external stimuli such as nutrient limitation. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Identification of genes encoding granule-bound starch synthase involved in amylose metabolism in banana fruit.

    Directory of Open Access Journals (Sweden)

    Hongxia Miao

    Full Text Available Granule-bound starch synthase (GBSS is responsible for amylose synthesis, but the role of GBSS genes and their encoded proteins remains poorly understood in banana. In this study, amylose content and GBSS activity gradually increased during development of the banana fruit, and decreased during storage of the mature fruit. GBSS protein in banana starch granules was approximately 55.0 kDa. The protein was up-regulated expression during development while it was down-regulated expression during storage. Six genes, designated as MaGBSSI-1, MaGBSSI-2, MaGBSSI-3, MaGBSSI-4, MaGBSSII-1, and MaGBSSII-2, were cloned and characterized from banana fruit. Among the six genes, the expression pattern of MaGBSSI-3 was the most consistent with the changes in amylose content, GBSS enzyme activity, GBSS protein levels, and the quantity or size of starch granules in banana fruit. These results suggest that MaGBSSI-3 might regulate amylose metabolism by affecting the variation of GBSS levels and the quantity or size of starch granules in banana fruit during development or storage.

  3. Identification of Genes Encoding Granule-Bound Starch Synthase Involved in Amylose Metabolism in Banana Fruit

    Science.gov (United States)

    Liu, Weixin; Xu, Biyu; Jin, Zhiqiang

    2014-01-01

    Granule-bound starch synthase (GBSS) is responsible for amylose synthesis, but the role of GBSS genes and their encoded proteins remains poorly understood in banana. In this study, amylose content and GBSS activity gradually increased during development of the banana fruit, and decreased during storage of the mature fruit. GBSS protein in banana starch granules was approximately 55.0 kDa. The protein was up-regulated expression during development while it was down-regulated expression during storage. Six genes, designated as MaGBSSI-1, MaGBSSI-2, MaGBSSI-3, MaGBSSI-4, MaGBSSII-1, and MaGBSSII-2, were cloned and characterized from banana fruit. Among the six genes, the expression pattern of MaGBSSI-3 was the most consistent with the changes in amylose content, GBSS enzyme activity, GBSS protein levels, and the quantity or size of starch granules in banana fruit. These results suggest that MaGBSSI-3 might regulate amylose metabolism by affecting the variation of GBSS levels and the quantity or size of starch granules in banana fruit during development or storage. PMID:24505384

  4. Vaccine adjuvants: Tailor-made mast-cell granules

    Science.gov (United States)

    Gunzer, Matthias

    2012-03-01

    Mast cells induce protective immune responses through secretion of stimulatory granules. Microparticles modelled after mast-cell granules are now shown to replicate and enhance the functions of their natural counterparts and to direct the character of the resulting immunity.

  5. Feeder-cell-independent culture of the pig-embryonic-stem-cell-derived exocrine pancreatic cell line, PICM-31

    Science.gov (United States)

    The adaptation to feeder-independent growth of a pig embryonic stem cell-derived pancreatic cell line is described. The parental PICM-31 cell line, previously characterized as an exocrine pancreas cell line, was colony-cloned two times in succession resulting in the subclonal cell line, PICM-31A1. P...

  6. Pancreas Transplantation With Portal-Enteric Drainage for Patients With Endocrine and Exocrine Insufficiency From Extensive Pancreatic Resection

    Directory of Open Access Journals (Sweden)

    Andrew S. Barbas, MD

    2017-09-01

    Full Text Available Abstract. Although the primary indication for pancreas transplantation is type I diabetes, a small number of patients requires pancreas transplantation to manage combined endocrine and exocrine insufficiency that develops after extensive native pancreatic resection. The objective of this case report was to describe the operative and clinical course in 3 such patients and present an alternative technical approach.

  7. Pancreas Transplantation With Portal-Enteric Drainage for Patients With Endocrine and Exocrine Insufficiency From Extensive Pancreatic Resection.

    Science.gov (United States)

    Barbas, Andrew S; Al-Adra, David P; Goldaracena, Nicolas; Dib, Martin J; Selzner, Markus; Sapisochin, Gonzalo; Cattral, Mark S; McGilvray, Ian D

    2017-09-01

    Although the primary indication for pancreas transplantation is type I diabetes, a small number of patients requires pancreas transplantation to manage combined endocrine and exocrine insufficiency that develops after extensive native pancreatic resection. The objective of this case report was to describe the operative and clinical course in 3 such patients and present an alternative technical approach.

  8. Pancreatic endocrine and exocrine function and salivary gland function in autoimmune pancreatitis before and after steroid therapy.

    Science.gov (United States)

    Kamisawa, Terumi; Egawa, Naoto; Inokuma, Shigeko; Tsuruta, Kouji; Okamoto, Atsutake; Kamata, Noriko; Nakamura, Teruo; Matsukawa, Masakatsu

    2003-10-01

    Autoimmune pancreatitis (AIP) is a distinct clinical entity in which an autoimmune mechanism may be involved in pathogenesis. To investigate salivary gland function in addition to pancreatic endocrine and exocrine function in patients with AIP, and to determine changes occurring after steroid therapy. Fasting serum glucose levels, oral glucose tolerance tests or glycosylated hemoglobin values were examined in 19 patients with AIP. N-benzoyl-L-tyrosyl-p-aminobenzoic acid excretion test, sialochemistry and parotid gland scintigraphy were performed in 8 patients. Eight patients had evidence of DM. Steroid therapy subsequently improved insulin secretion and glycemic control in 3 of 5 patients treated. Pancreatic exocrine function was reduced in 88% of patients. Impaired pancreatic exocrine function improved after steroid therapy in 3 of 6 patients treated. The 3 patients also showed treatment-related improvement in endocrine function. Concentration of beta2-microglobulin in saliva was significantly raised in patients with AIP compared with controls (P gland dysfunction improved after steroid therapy in all 5 patients treated. Pancreatic endocrine and exocrine and salivary gland function were frequently impaired in patients with AIP, and steroid therapy was occasionally effective for these dysfunctions.

  9. Breakage and drying behaviour of granules in a continuous fluid bed dryer: Influence of process parameters and wet granule transfer.

    Science.gov (United States)

    De Leersnyder, F; Vanhoorne, V; Bekaert, H; Vercruysse, J; Ghijs, M; Bostijn, N; Verstraeten, M; Cappuyns, P; Van Assche, I; Vander Heyden, Y; Ziemons, E; Remon, J P; Nopens, I; Vervaet, C; De Beer, T

    2018-03-30

    Although twin screw granulation has already been widely studied in recent years, only few studies addressed the subsequent continuous drying which is required after wet granulation and still suffers from a lack of detailed understanding. The latter is important for optimisation and control and, hence, a cost-effective practical implementation. Therefore, the aim of the current study is to increase understanding of the drying kinetics and the breakage and attrition phenomena during fluid bed drying after continuous twin screw granulation. Experiments were performed on a continuous manufacturing line consisting of a twin-screw granulator, a six-segmented fluid bed dryer, a mill, a lubricant blender and a tablet press. Granulation parameters were fixed in order to only examine the effect of drying parameters (filling time, drying time, air flow, drying air temperature) on the size distribution and moisture content of granules (both of the entire granulate and of size fractions). The wet granules were transferred either gravimetrically or pneumatically from the granulator exit to the fluid bed dryer. After a certain drying time, the moisture content reached an equilibrium. This drying time was found to depend on the applied airflow, drying air temperature and filling time. The moisture content of the granules decreased with an increasing drying time, airflow and drying temperature. Although smaller granules dried faster, the multimodal particle size distribution of the granules did not compromise uniform drying of the granules when the target moisture content was achieved. Extensive breakage of granules was observed during drying. Especially wet granules were prone to breakage and attrition during pneumatic transport, either in the wet transfer line or in the dry transfer line. Breakage and attrition of granules during transport and drying should be anticipated early on during process and formulation development by performing integrated experiments on the granulator

  10. Reduced Insulin/IGF-1 Signaling Restores the Dynamic Properties of Key Stress Granule Proteins during Aging

    Directory of Open Access Journals (Sweden)

    Marie C. Lechler

    2017-01-01

    Full Text Available Summary: Low-complexity “prion-like” domains in key RNA-binding proteins (RBPs mediate the reversible assembly of RNA granules. Individual RBPs harboring these domains have been linked to specific neurodegenerative diseases. Although their aggregation in neurodegeneration has been extensively characterized, it remains unknown how the process of aging disturbs RBP dynamics. We show that a wide variety of RNA granule components, including stress granule proteins, become highly insoluble with age in C. elegans and that reduced insulin/insulin-like growth factor 1 (IGF-1 daf-2 receptor signaling efficiently prevents their aggregation. Importantly, stress-granule-related RBP aggregates are associated with reduced fitness. We show that heat shock transcription factor 1 (HSF-1 is a main regulator of stress-granule-related RBP aggregation in both young and aged animals. During aging, increasing DAF-16 activity restores dynamic stress-granule-related RBPs, partly by decreasing the buildup of other misfolded proteins that seed RBP aggregation. Longevity-associated mechanisms found to maintain dynamic RBPs during aging could be relevant for neurodegenerative diseases. : Lechler et al. show that RNA-binding proteins (RBPs including stress granule proteins are prone to aggregate with age in C. elegans. Aggregation of stress granule RBPs with “prion-like” domains is associated with reduced fitness. Their aggregation is prevented by longevity pathways and promoted by the aggregation of other misfolded proteins. Keywords: neurodegenerative diseases, Caenorhabditis elegans, protein aggregation, aging, RNA-binding proteins, stress granules, HSF-1, DAF-2, longevity

  11. Sodium phenylbutyrate coated granules (Pheburane). Defective urea synthesis: a welcome formulation.

    Science.gov (United States)

    2015-02-01

    Compared with Ammonaps granules, Pheburane coated granules mask the unpleasant taste of sodium phenylbutyrate. A more precise dosing device is provided with the coated granules than with the uncoated granules (Ammonaps).

  12. Detection and Analysis of the Quality of Ibuprofen Granules

    Science.gov (United States)

    Yu-bin, Ji; Xin, LI; Guo-song, Xin; Qin-bing, Xue

    2017-12-01

    The Ibuprofen Granules comprehensive quality testing to ensure that it is in accordance with the provisions of Chinese pharmacopoeia. With reference of Chinese pharmacopoeia, the Ibuprofen Granules is tested by UV, HPLC, in terms of grain size checking, volume deviation, weight loss on drying detection, dissolution rate detection, and quality evaluation. Results indicated that Ibuprofen Granules conform to the standards. The Ibuprofen Granules are qualified and should be permitted to be marketed.

  13. Tracheostomy Decannulation: Suprastomal Granulation Tissue in ...

    African Journals Online (AJOL)

    Background: Suprastomal granulation tissue is a complication of tracheostomy which may make decannulation difficult and presents a therapeutic challenge to the Otorhinolaryngologists. The aims of this study therefore were to evaluate tracheostomy in black African population, determine the prevalence of suprastomal ...

  14. Atrial natriuretic peptide (ANP)-granules: ultrastructure ...

    African Journals Online (AJOL)

    ANP) are present in the four regions of the atrial-auricular complex (two atria and two auricles). ANP-immunoreactivity was detected in all granules from the four regions. Ultrastructurally, atrial myocytes show the presence of very electron dense ...

  15. 21 CFR 520.1468 - Naproxen granules.

    Science.gov (United States)

    2010-04-01

    ... and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.1468 Naproxen granules. (a... musculoskeletal system of the horse. (2)(i) For oral maintenance therapy following initial intravenous dosage...

  16. Water Filtration through Homogeneous Granulated Charge

    Directory of Open Access Journals (Sweden)

    A. M. Krautsou

    2005-01-01

    Full Text Available General relationship for calculation of water filtration through homogeneous granulated charge has been obtained. The obtained relationship has been compared with experimental data. Discrepancies between calculated and experimental values do not exceed 6 % throughout the entire investigated range.

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

    International Nuclear Information System (INIS)

    Wan Haiyan; Korzh, Svitlana; Li Zhen; Mudumana, Sudha Puttur; Korzh, Vladimir; Jiang Yunjin; Lin Shuo; Gong Zhiyuan

    2006-01-01

    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

  18. The influence of granulating solvents on drug release from tablets ...

    African Journals Online (AJOL)

    ... significantly lower than the other wet granulated tablets, but higher than the matrix tablets. The granulating solvent influenced the release of drug which increased with increase in the water content. Key Words: Grewia gum: Granulating solvents; Release mechanisms. Journal of Pharmacy and Bioresources Vol.1(1) 2004: ...

  19. 21 CFR 520.905b - Fenbendazole granules.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Fenbendazole granules. 520.905b Section 520.905b... DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.905b Fenbendazole granules. (a) Specifications. Each gram of granules contains 222 milligrams (mg) fenbendazole. (b) Sponsor. See...

  20. Mouse pancreas tissue slice culture facilitates long-term studies of exocrine and endocrine cell physiology in situ.

    Science.gov (United States)

    Marciniak, Anja; Selck, Claudia; Friedrich, Betty; Speier, Stephan

    2013-01-01

    Studies on pancreatic cell physiology rely on the investigation of exocrine and endocrine cells in vitro. Particularly, in the case of the exocrine tissue these studies have suffered from a reduced functional viability of acinar cells in culture. As a result not only investigations on dispersed acinar cells and isolated acini were limited in their potential, but also prolonged studies on pancreatic exocrine and endocrine cells in an intact pancreatic tissue environment were unfeasible. To overcome these limitations, we aimed to establish a pancreas tissue slice culture platform to allow long-term studies on exocrine and endocrine cells in the intact pancreatic environment. Mouse pancreas tissue slice morphology was assessed to determine optimal long-term culture settings for intact pancreatic tissue. Utilizing optimized culture conditions, cell specificity and function of exocrine acinar cells and endocrine beta cells were characterized over a culture period of 7 days. We found pancreas tissue slices cultured under optimized conditions to have intact tissue specific morphology for the entire culture period. Amylase positive intact acini were present at all time points of culture and acinar cells displayed a typical strong cell polarity. Amylase release from pancreas tissue slices decreased during culture, but maintained the characteristic bell-shaped dose-response curve to increasing caerulein concentrations and a ca. 4-fold maximal over basal release. Additionally, endocrine beta cell viability and function was well preserved until the end of the observation period. Our results show that the tissue slice culture platform provides unprecedented maintenance of pancreatic tissue specific morphology and function over a culture period for at least 4 days and in part even up to 1 week. This analytical advancement now allows mid -to long-term studies on the cell biology of pancreatic disorder pathogenesis and therapy in an intact surrounding in situ.

  1. Mouse pancreas tissue slice culture facilitates long-term studies of exocrine and endocrine cell physiology in situ.

    Directory of Open Access Journals (Sweden)

    Anja Marciniak

    Full Text Available Studies on pancreatic cell physiology rely on the investigation of exocrine and endocrine cells in vitro. Particularly, in the case of the exocrine tissue these studies have suffered from a reduced functional viability of acinar cells in culture. As a result not only investigations on dispersed acinar cells and isolated acini were limited in their potential, but also prolonged studies on pancreatic exocrine and endocrine cells in an intact pancreatic tissue environment were unfeasible. To overcome these limitations, we aimed to establish a pancreas tissue slice culture platform to allow long-term studies on exocrine and endocrine cells in the intact pancreatic environment. Mouse pancreas tissue slice morphology was assessed to determine optimal long-term culture settings for intact pancreatic tissue. Utilizing optimized culture conditions, cell specificity and function of exocrine acinar cells and endocrine beta cells were characterized over a culture period of 7 days. We found pancreas tissue slices cultured under optimized conditions to have intact tissue specific morphology for the entire culture period. Amylase positive intact acini were present at all time points of culture and acinar cells displayed a typical strong cell polarity. Amylase release from pancreas tissue slices decreased during culture, but maintained the characteristic bell-shaped dose-response curve to increasing caerulein concentrations and a ca. 4-fold maximal over basal release. Additionally, endocrine beta cell viability and function was well preserved until the end of the observation period. Our results show that the tissue slice culture platform provides unprecedented maintenance of pancreatic tissue specific morphology and function over a culture period for at least 4 days and in part even up to 1 week. This analytical advancement now allows mid -to long-term studies on the cell biology of pancreatic disorder pathogenesis and therapy in an intact surrounding in situ.

  2. Determinants of exocrine pancreatic function as measured by fecal elastase-1 concentrations (FEC in patients with diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Ewald N

    2009-03-01

    Full Text Available Abstract Objective Recently it has been shown that there is not only endocrine insufficiency in diabetic patients, but a frequent co-morbidity of both, the endocrine and exocrine pancreas. The present study was performed to further analyse the determinants of exocrine pancreatic function in patients with diabetes mellitus. Methods The records of 1992 patients with diabetes mellitus who had been treated in our hospital during a 2-year period were re-evaluated. Defined parameters were documented in standardized data sheets. Records were further checked for the results of imaging procedures of the pancreas. In 307 patients FEC had been performed and documented. Only these patients were included in further evaluation. Results FEC was inversely correlated with diabetes duration and HbA1c-levels but not with age. C-peptide levels correlated positively with FEC. BMI and FEC were also significantly correlated. There was no correlation between diabetes therapy and exocrine pancreatic function as there was no correlation with any concomitant medication. The presence of diabetes-associated antibodies was not related to FEC. According to the documented data 38 were classified as type-1 diabetes (12.4%, 167 as type-2 (54.4%, and 88 patients met the diagnostic criteria of type-3 (28.7%. Fourteen patients could not be classified because of lacking information (4.6%. Conclusions Exocrine insufficiency might be explained as a complication of diabetes mellitus. However, it is more likely that type-3 diabetes is much more frequent than previously believed. Consequently the evaluation of exocrine function and morphology should be included into the clinical workup of any diabetic patient at least at the time of manifestation.

  3. Amylolytic hydrolysis of native starch granules affected by granule surface area.

    Science.gov (United States)

    Kim, J C; Kong, B W; Kim, M J; Lee, S H

    2008-11-01

    Initial stage of hydrolysis of native starch granules with various amylolytic enzymes, alpha-amylase from Bacillus subtilis, glucoamylase I (GA-I) and II (GA-II) from Aspergillus niger, and beta-amylase from sweet potato showed that the reaction was apparently affected by a specific surface area of the starch granules. The ratios of the reciprocal of initial velocity of each amylolytic hydrolysis for native potato and maize starch to that for rice with the amylolytic enzymes were nearly equivalent to the ratio of surface area per mass of the 2 starch granules to that of rice, that is, 6.94 and 2.25, respectively. Thus, the reciprocal of initial velocity of each enzymatic hydrolysis as expressed in a Lineweaver-Burk plot was a linear function of the reciprocal of surface area for each starch granule. As a result, it is concluded that amylolytic hydrolysis of native starch granules is governed by the specific surface area, not by the mass concentration, of each granule.

  4. Adrenergic effects on exocrine secretion of rat submandibular epidermal growth factor

    DEFF Research Database (Denmark)

    Poulsen, Steen Seier; Nexø, Ebba

    1984-01-01

    The present study was undertaken to investigate the effect of alpha- and beta-adrenergic agonists on secretion of epidermal growth factor (EGF) from the rat submandibular glands and to test the possibility of intestinal absorption of EGF. Alpha-adrenergic agonists increased the concentration...... of salivary EGF by approximately a hundred times, while the serum concentration of EGF was unchanged. The contents of EGF in the submandibular glands decreased upon administration of the alpha-adrenergic agonist noradrenaline, and this was confirmed on immunohistochemical investigation of the glands. Beta-adrenergic....... This study shows that alpha-adrenergic agonists stimulate exocrine secretion of submandibular EGF and that EGF in physiological amounts are not absorbed in the gastrointestinal tract....

  5. A radiopharmaceutical for pancreatic exocrine functional diagnosis: 62Zn-EDDA metabolism in pancreas.

    Science.gov (United States)

    Fujibayashi, Y; Saji, H; Kawai, K; Unuma, Y; Miyata, S; Okuno, T; Hosotani, R; Inoue, K; Adachi, H; Horiuchi, K

    1986-01-01

    The metabolic pathway of radioactive 62Zn-EDDA (ethylenediamine-N,N'-diacetic acid), in the exocrine pancreas was studied with respect to that of endogenous Zn. In pancreatic duct cannulated dog, the secretion of intravenously injected exogenous 62Zn into pancreatic juice increased under the stimulation of CCK-PZ (pancreatic protein secretion stimulating hormone), which closely correlated to endogenous Zn. Moreover, in pancreatic juice, 62Zn as well as endogenous Zn was selectively bound to Zn-metalloenzymes, carboxypeptidase A and B. These results demonstrated the close correlation between the endogenous and the exogenously-administered Zn (62Zn-EDDA), as well as the high availability of 62Zn-EDDA as a marker of pancreatic function for the follow up of carboxypeptidase metabolism.

  6. CA 19-9 in the diagnosis and differential diagnosis of exocrine pancreatic carcinoma

    International Nuclear Information System (INIS)

    Klapdor, R.; Lehmann, U.; Bahlo, M.; Greten, H.; Ackeren, H. v.; Dallek, M.; Schreiber, W.H.

    1983-01-01

    CA 19-9 serum concentrations were determined in 56 controls and 66 patients with various pancreatic diseases using a commercially available radioimmunoassay. 56 controls showed mean serum concentrations of 7.3 +- 9.6 U/ml (anti x +- 2 SD) range 0-24, median 6), n = 21 patients suffering from chronic pancreatitis mean values of 16 +- 24 U/ml (anti x +- 2 SD) (range 4.9-42, median 13). The majority of the patients with exocrine pancreatic carcinoma demonstrated significantly elevated values: in 91% and 82% respectively, CA 19-9 levels were elevated above the upper limit of 95% of the controls (> 15 U/ml) and of the patients with chronic pancreatitis (> 37 U/ml) (P [de

  7. Monitoring the effect of substitution therapy in patients with exocrine pancreatic insufficiency

    International Nuclear Information System (INIS)

    Joergensen, B.B.; Pedersen, N.T.; Worning, H.

    1991-01-01

    Twenty-three outpatients with chronic pancreatitis and severe exocrine insufficiency were studied for the purpose of comparing the effect of Pancrease, Pankreon and Pankreatin by estimation of duodenal enzyme activity, the faecal fat excretion, and the faecal 14 C-triolein- 3 H-oleic acid test and, at the same time, to evaluate these tests when monitoring outpatients. The three preparations did not disclose any significant difference in treating steatorrhoea. Pankreatin increased the meal-stimulated duodenal enzyme activity (p 14 -C-triolein- 3 H-oleic acid test showed significant improvement in the 14 C-triolein digestion with all three preparations (p 14 -C-triolein- 3 H-oleic acid test was the most reliable when monitoring outpatients. 17 refs., 1 fig., 3 tabs

  8. Radioselenium pancreozymin-secretin test as a clinical test for pancreatic exocrine function

    International Nuclear Information System (INIS)

    Shichiri, M.; Etani, N.; Yoshida, M.; Harano, Y.; Hoshi, M.; Shigeta, Y.; Abe, H.

    1975-01-01

    The appearance of radioselenium in the protein fraction of duodenal aspirates has been studied after an intravenous injection of 75 Se-selenomethionine. The continuous flow of pancreatic juice was stimulated by pancreozymin at 120 minutes and by secretin at 140 minutes. A good distinction between normal subjects and patients with pancreatic disease was obtained by measuring 75 Se-radioactivity in the protein fraction of duodenal aspirates; either cumulative radioactivity during the combined 80-minute post-pancreozymin-secretin period, or maximum 75 Se-specific activity during the postsecretin period was used as an index. The test presented here might be a useful and sufficiently reliable method for detecting abnormal pancreatic exocrine function. This test can be performed along with the conventional pancreozymin-secretin test, serum enzyme response to pancreozymin and secretin, and pancreatic scintiscanning

  9. Non-invasive quantification of pancreatic exocrine function using secretin-stimulated MRCP

    International Nuclear Information System (INIS)

    Punwani, S.; Gillams, A.R.; Lees, W.R.

    2003-01-01

    Our objective was to quantify water volume using magnetic resonance cholangiopancreatography (MRCP) sequences and apply this to secretin-stimulated studies with the aim of quantifying pancreatic exocrine function. A commercially available single-shot MRCP sequence was used in conjunction with a body phased-array coil and a 1.5-T MR system. Signal intensity was measured in samples of water, pancreatic, duodenal juice, and secretin-stimulated pancreatic juice. A water phantom was made and MR calculated volumes compared with known water volumes within the phantom. Changes in small intestinal volume in response to secretin were measured in a group of 11 patients with no evidence of pancreatic disease. Changes in water volume were plotted over time. The pancreatic duct diameter before and after secretin was noted and filling defects were sought. All patients also underwent an axial breath-hold T1-weighted gradient-echo sequence and the pancreatic parenchyma was evaluated for size and signal intensity. There was no difference in the signal intensity of the different juice samples. There was excellent correlation between known and calculated MRCP volumes (χ 2 =0.99). All patients demonstrated normal duct morphology on MRCP and normal pancreatic parenchyma on T1-weighted imaging. The mean flow rate in the patient population was 8.1±2.5 ml/s over a median of 7 min (range 5-9 min). The MRCP sequence can be used to measure water volume. Sequential MRCP measurements following secretin permitted calculation of volume change and flow rate. This should prove useful as an indicator of pancreatic exocrine function. (orig.)

  10. Exocrine glands of Lepeophtheirus salmonis (Copepoda: Caligidae): Distribution, developmental appearance, and site of secretion.

    Science.gov (United States)

    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.

  11. Granulation of snow: From tumbler experiments to discrete element simulations

    Science.gov (United States)

    Steinkogler, Walter; Gaume, Johan; Löwe, Henning; Sovilla, Betty; Lehning, Michael

    2015-06-01

    It is well known that snow avalanches exhibit granulation phenomena, i.e., the formation of large and apparently stable snow granules during the flow. The size distribution of the granules has an influence on flow behavior which, in turn, affects runout distances and avalanche velocities. The underlying mechanisms of granule formation are notoriously difficult to investigate within large-scale field experiments, due to limitations in the scope for measuring temperatures, velocities, and size distributions. To address this issue we present experiments with a concrete tumbler, which provide an appropriate means to investigate granule formation of snow. In a set of experiments at constant rotation velocity with varying temperatures and water content, we demonstrate that temperature has a major impact on the formation of granules. The experiments showed that granules only formed when the snow temperature exceeded -1∘C. No evolution in the granule size was observed at colder temperatures. Depending on the conditions, different granulation regimes are obtained, which are qualitatively classified according to their persistence and size distribution. The potential of granulation of snow in a tumbler is further demonstrated by showing that generic features of the experiments can be reproduced by cohesive discrete element simulations. The proposed discrete element model mimics the competition between cohesive forces, which promote aggregation, and impact forces, which induce fragmentation, and supports the interpretation of the granule regime classification obtained from the tumbler experiments. Generalizations, implications for flow dynamics, and experimental and model limitations as well as suggestions for future work are discussed.

  12. Vasoactive Intestinal Peptide Protects Salivary Glands against Structural Injury and Secretory Dysfunction via IL-17A and AQP5 Regulation in a Model of Sjögren Syndrome.

    Science.gov (United States)

    Li, Chengyin; Zhu, Fenglin; Wu, Bin; Wang, Yue

    2018-04-04

    Sjögren syndrome (SS) is an autoimmune disease involving exocrine glands. Currently, drugs that can improve both abnormal immunity and exocrine gland function are needed. The study aimed to investigate the effect and mechanism of vasoactive intestinal peptide (VIP) on the immune response and exocrine gland function in SS. We investigated the effects of VIP on the immune response and secretory function of submandibular glands using NOD mice, and analyzed the expression of IL-17A and AQP5 (aquaporin 5). The submandibular gland cells from healthy 8-day-old Sprague-Dawley rats were used to observe the influence of VIP on AQP5 expression. Our study shows that treatment with VIP in an SS mouse model could not only reduce the immune injury to exocrine glands but also improve the secretory function of these glands. Furthermore, VIP was shown to improve the abnormal immune status by downregulating IL-17A expression in the exocrine glands. It also enhanced the secretory function of exocrine glands by upregulating AQP5 expression. Using a model of SS, we found that VIP could not only modulate the immune response but also affect exocrine gland function, and that these therapeutic effects were associated with IL-17A and AQP5 regulation. © 2018 S. Karger AG, Basel.

  13. Factors Involved in Sludge Granulation under Anaerobic Conditions

    Directory of Open Access Journals (Sweden)

    Jalal Shayegan

    2011-03-01

    Full Text Available This paper investigates the effects of factors involved in sludge anaerobic granulation. Granulated sludge formation is the main parameter contributing to the success of UASB reactors. Anaerobic granulation leads to reduced reactor size, space requirement, and investment costs. Operation costs are also greatly reduced due to lack of aeration. An important parameter affecting process performance is the size of sludge granules; the factors involved in granule size will be investigated. Some of the important parameters of anaerobic sludge granulation are: existence of growth cores as inert particles or granulated sludge, process operational conditions (Sludge Loading Rate and Organic Loading Rate, Loading rate increase and …, and environment conditions (nutrients, temperature, pH, combination and ….

  14. Giant renin secretory granules in beige mouse renal afferent arterioles

    DEFF Research Database (Denmark)

    Jensen, B L; Rasch, Ruth; Nyengaard, Jens Randel

    1997-01-01

    The mutant beige mouse (C57BL/6 bg) has a disease characterised by abnormally enlarged cytoplasmic granules in a variety of cells. With the purpose of establishing a suitable cellular model for studying renin secretion, the present study was undertaken to compare renin granule morphology in beige...... (average granular volume 0.681 microm3), whereas 1-2 large granules were present per cell in beige mice. The volume of afferent arteriole that contained secretory granules was lower in the beige mice. We conclude that the beige mouse synthesizes, stores and releases active renin. Renin secretory granules...... in beige mice are grossly enlarged with 1-2 granules per juxtaglomerular cell. Compared with control mice, a similar amount of total renin granule volume per afferent arteriole is contained in a smaller part of beige mouse afferent arteriole. Granular cells from beige mice could therefore be a valuable...

  15. Increased accuracy of starch granule type quantification using mixture distributions.

    Science.gov (United States)

    Tanaka, Emi; Ral, Jean-Phillippe F; Li, Sean; Gaire, Raj; Cavanagh, Colin R; Cullis, Brian R; Whan, Alex

    2017-01-01

    The proportion of granule types in wheat starch is an important characteristic that can affect its functionality. It is widely accepted that granule types are either large, disc-shaped A-type granules or small, spherical B-type granules. Additionally, there are some reports of the tiny C-type granules. The differences between these granule types are due to its carbohydrate composition and crystallinity which is highly, but not perfectly, correlated with the granule size. A majority of the studies that have considered granule types analyse them based on a size threshold rather than chemical composition. This is understandable due to the expense of separating starch into different types. While the use of a size threshold to classify granule type is a low-cost measure, this results in misclassification. We present an alternative, statistical method to quantify the proportion of granule types by a fit of the mixture distribution, along with an R package, a web based app and a video tutorial for how to use the web app to enable its straightforward application. Our results show that the reliability of the genotypic effects increase approximately 60% using the proportions of the A-type and B-type granule estimated by the mixture distribution over the standard size-threshold measure. Although there was a marginal drop in reliability for C-type granules. The latter is likely due to the low observed genetic variance for C-type granules. The determination of the proportion of granule types from size-distribution is better achieved by using the mixing probabilities from the fit of the mixture distribution rather than using a size-threshold.

  16. Microbial granulation for lactic acid production

    DEFF Research Database (Denmark)

    Kim, Dong-Hoon; Lee, Mo-Kwon; Hwang, Yuhoon

    2016-01-01

    This work investigated the formation of microbial granules to boost the productivity of lactic acid (LA). The flocculated form of LA-producing microbial consortium, dominated by Lactobacillus sp. (91.5% of total sequence), was initially obtained in a continuous stirred-tank reactor (CSTR), which...... increased, reaching 67 g L-fermenter−1h−1 at HRT 0.17 h. The size of LA-producing granules and hydrophobicity gradually increased with decrease in HRT, reaching 6.0 mm and 60%, respectively. These biogranules were also found to have high settling velocities and low porosities, ranging 2.69-4.73 cm s−1 and 0...

  17. PTEN deletion from adult-generated dentate granule cells disrupts granule cell mossy fiber axon structure.

    Science.gov (United States)

    LaSarge, Candi L; Santos, Victor R; Danzer, Steve C

    2015-03-01

    Dysregulation of the mTOR-signaling pathway is implicated in the development of temporal lobe epilepsy. In mice, deletion of PTEN from hippocampal dentate granule cells leads to mTOR hyperactivation and promotes the rapid onset of spontaneous seizures. The mechanism by which these abnormal cells initiate epileptogenesis, however, is unclear. PTEN-knockout granule cells develop abnormally, exhibiting morphological features indicative of increased excitatory input. If these cells are directly responsible for seizure genesis, it follows that they should also possess increased output. To test this prediction, dentate granule cell axon morphology was quantified in control and PTEN-knockout mice. Unexpectedly, PTEN deletion increased giant mossy fiber bouton spacing along the axon length, suggesting reduced innervation of CA3. Increased width of the mossy fiber axon pathway in stratum lucidum, however, which likely reflects an unusual increase in mossy fiber axon collateralization in this region, offsets the reduction in boutons per axon length. These morphological changes predict a net increase in granule cell innervation of CA3. Increased diameter of axons from PTEN-knockout cells would further enhance granule cell communication with CA3. Altogether, these findings suggest that amplified information flow through the hippocampal circuit contributes to seizure occurrence in the PTEN-knockout mouse model of temporal lobe epilepsy. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Granule fraction inhomogeneity of calcium carbonate/sorbitol in roller compacted granules

    DEFF Research Database (Denmark)

    Bacher, Charlotte; Olsen, P.M.; Bertelsen, P.

    2008-01-01

    The granule fraction inhomogeneity of roller compacted granules was examined on mixtures of three different morphologic forms of calcium carbonate and three particle sizes of sorbitol. The granule fraction inhomogeneity was determined by the distribution of the calcium carbonate in each of the 10...... size fractions between 0 and 2000 µm and by calculating the demixing potential. Significant inhomogeneous occurrence of calcium carbonate in the size fractions was demonstrated, depending mostly on the particles sizes of sorbitol but also on the morphological forms of calcium carbonate......, the ability of the powder to agglomerate in the roller compactor was demonstrated to be related to the ability of the powder to be compacted into a tablet, thus the most compactable calcium carbonate and the smallest sized sorbitol improved the homogeneity by decreasing the demixing potential....

  19. A new type of exocrine gland and its function in mass recruitment in the ant Cylindromyrmex whymperi (Formicidae, Cerapachyinae)

    Science.gov (United States)

    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.

  20. Noninvasive investigation of exocrine pancreatic function: Feasibility of cine dynamic MRCP with a spatially selective inversion-recovery pulse.

    Science.gov (United States)

    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 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.

  1. The density of parasympathetic axons is reduced in the exocrine pancreas of individuals recently diagnosed with type 1 diabetes.

    Science.gov (United States)

    Lundberg, Marcus; Lindqvist, Andreas; Wierup, Nils; Krogvold, Lars; Dahl-Jørgensen, Knut; Skog, Oskar

    2017-01-01

    To elucidate the etiology of type 1 diabetes, the affected pancreas needs to be thoroughly characterized. Pancreatic innervation has been suggested to be involved in the pathology of the disease and a reduction of sympathetic innervation of the islets was recently reported. In the present study, we hypothesized that parasympathetic innervation would be altered in the type 1 diabetes pancreas. Human pancreatic specimens were obtained from a unique cohort of individuals with recent onset or long standing type 1 diabetes. Density of parasympathetic axons was assessed by immunofluorescence and morphometry. Our main finding was a reduced density of parasympathetic axons in the exocrine, but not endocrine compartment of the pancreas in individuals with recent onset type 1 diabetes. The reduced density of parasympathetic axons in the exocrine compartment could have functional implications, e.g. be related to the exocrine insufficiency reported in type 1 diabetes patients. Further studies are needed to understand whether reduced parasympathetic innervation is a cause or consequence of type 1 diabetes.

  2. The density of parasympathetic axons is reduced in the exocrine pancreas of individuals recently diagnosed with type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Marcus Lundberg

    Full Text Available To elucidate the etiology of type 1 diabetes, the affected pancreas needs to be thoroughly characterized. Pancreatic innervation has been suggested to be involved in the pathology of the disease and a reduction of sympathetic innervation of the islets was recently reported. In the present study, we hypothesized that parasympathetic innervation would be altered in the type 1 diabetes pancreas. Human pancreatic specimens were obtained from a unique cohort of individuals with recent onset or long standing type 1 diabetes. Density of parasympathetic axons was assessed by immunofluorescence and morphometry. Our main finding was a reduced density of parasympathetic axons in the exocrine, but not endocrine compartment of the pancreas in individuals with recent onset type 1 diabetes. The reduced density of parasympathetic axons in the exocrine compartment could have functional implications, e.g. be related to the exocrine insufficiency reported in type 1 diabetes patients. Further studies are needed to understand whether reduced parasympathetic innervation is a cause or consequence of type 1 diabetes.

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

    Science.gov (United States)

    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

  4. Predictors of Locoregional Failure and Impact on Overall Survival in Patients With Resected Exocrine Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Merrell, Kenneth W.; Haddock, Michael G. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Quevedo, J. Fernando [Division of Medical Oncology, Mayo Clinic, Rochester, Minnesota (United States); Harmsen, William S. [Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota (United States); Kendrick, Michael L. [Department of General Surgery, Mayo Clinic, Rochester, Minnesota (United States); Miller, Robert C. [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States); Hallemeier, Christopher L., E-mail: hallemeier.christopher@mayo.edu [Department of Radiation Oncology, Mayo Clinic, Rochester, Minnesota (United States)

    2016-03-01

    Purpose: Resection of exocrine pancreatic cancer is necessary for cure, but locoregional and distant relapse is common. We evaluated our institutional experience to better understand risk factors for locoregional failure (LRF) and its impact on overall survival (OS). Methods and Materials: We reviewed 1051 consecutive patients with nonmetastatic exocrine pancreatic cancer who underwent resection at our institution between March 1987 and January 2011. Among them, 458 had adequate follow-up and evaluation for study inclusion. All patients received adjuvant chemotherapy (n=80 [17.5%]) or chemoradiation therapy (n=378 [82.5%]). Chemotherapy and chemoradiation therapy most frequently consisted of 6 cycles of gemcitabine and 50.4 Gy in 28 fractions with concurrent 5-fluorouracil, respectively. Locoregional control (LRC) and OS were estimated with the Kaplan-Meier method. Univariate and multivariate analyses were performed with Cox proportional hazards regression models incorporating propensity score. Results: Median patient age was 64.5 years (range: 29-88 years). Median follow-up for living patients was 84 months (range: 6-300 months). Extent of resection was R0 (83.8%) or R1 (16.2%). Overall crude incidence of LRF was 17% (n=79). The 5-year LRC for patients with and without radiation therapy was 80% and 68%, respectively (P=.003; hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.28-0.76). Multivariate analysis, incorporating propensity score, indicated radiation therapy (P<.0001; HR: 0.23; 95% CI: 0.12-0.42) and positive lymph node ratio of ≥0.2 (P=.02; HR: 1.78; 95% CI: 1.10-2.9) were associated with LRC. In addition, LRF was associated with worse OS (P<.0001; HR: 5.0; 95% CI: 3.9-6.3). Conclusions: In our analysis of 458 patients with resected pancreatic cancer, positive lymph node ratio of ≥0.2 and no adjuvant chemoradiation therapy were associated with increased LRF risk. LRF was associated with poor OS. Radiation therapy should be considered as

  5. Negotiating the complexities of exocrine and endocrine dysfunction in chronic pancreatitis.

    Science.gov (United States)

    Duggan, Sinead N

    2017-11-01

    Chronic pancreatitis is a chronic inflammatory disease of the pancreas characterised by irreversible morphological change and typically causing pain and/or permanent loss of function. This progressive, irreversible disease results in destruction of healthy pancreatic tissue and the development of fibrous scar tissue. Gradual loss of exocrine and endocrine function follows, along with clinical manifestations such as steatorrhoea, abdominal pain and diabetes. Nutrition in chronic pancreatitis has been described as a problem area and, until recently, there was little research on the topic. It is often asserted that >90 % of the pancreas must be damaged before exocrine insufficiency occurs; however, an exploration of the original studies from the 1970s found that the data do not support this assertion. The management of steatorrhoea with pancreatic enzyme replacement therapy is the mainstay of nutritional management, and early identification and treatment is a key. The presence of steatorrhoea, coupled with poor dietary intake (due to intractable abdominal pain, gastrointestinal side effects and often alcoholism) renders the chronic pancreatitis patients at considerable risk for undernutrition, muscle depletion and fat-soluble vitamin deficiency. Premature osteoporosis/osteopenia afflicts two-thirds of patients as a consequence of poor dietary intake of calcium and vitamin D, low physical activity, low sunlight exposure, heavy smoking, as well as chronic low-grade inflammation. Bone metabolism studies show increased bone formation as well as bone resorption in chronic pancreatitis, indicating that bone turnover is abnormally high. Loss of the pancreatic islet cells occurs later in the disease process as the endocrine cells are diffusely distributed throughout the pancreatic parenchyma. Patients may develop type 3c (pancreatogenic) diabetes, which is complicated by concurrent decreased glucagon secretion, and hence an increased risk of hypoglycaemia. Diabetes control is

  6. Visualization and understanding of the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging.

    Science.gov (United States)

    Vercruysse, Jurgen; Toiviainen, Maunu; Fonteyne, Margot; Helkimo, Niko; Ketolainen, Jarkko; Juuti, Mikko; Delaet, Urbain; Van Assche, Ivo; Remon, Jean Paul; Vervaet, Chris; De Beer, Thomas

    2014-04-01

    Over the last decade, there has been increased interest in the application of twin screw granulation as a continuous wet granulation technique for pharmaceutical drug formulations. However, the mixing of granulation liquid and powder material during the short residence time inside the screw chamber and the atypical particle size distribution (PSD) of granules produced by twin screw granulation is not yet fully understood. Therefore, this study aims at visualizing the granulation liquid mixing and distribution during continuous twin screw granulation using NIR chemical imaging. In first instance, the residence time of material inside the barrel was investigated as function of screw speed and moisture content followed by the visualization of the granulation liquid distribution as function of different formulation and process parameters (liquid feed rate, liquid addition method, screw configuration, moisture content and barrel filling degree). The link between moisture uniformity and granule size distributions was also studied. For residence time analysis, increased screw speed and lower moisture content resulted to a shorter mean residence time and narrower residence time distribution. Besides, the distribution of granulation liquid was more homogenous at higher moisture content and with more kneading zones on the granulator screws. After optimization of the screw configuration, a two-level full factorial experimental design was performed to evaluate the influence of moisture content, screw speed and powder feed rate on the mixing efficiency of the powder and liquid phase. From these results, it was concluded that only increasing the moisture content significantly improved the granulation liquid distribution. This study demonstrates that NIR chemical imaging is a fast and adequate measurement tool for allowing process visualization and hence for providing better process understanding of a continuous twin screw granulation system. Copyright © 2013 Elsevier B.V. All

  7. Giant arachnoid granulation in a patient with benign intracranial hypertension

    International Nuclear Information System (INIS)

    Kiroglu, Yilmaz; Yaqci, Baki; Cirak, Bayram; Karabulut, Nevzat

    2008-01-01

    We report magnetic resonance (MR), computed tomography (CT) and angiographic imaging of an unusual giant arachnoid granulation in the superior sagittal sinus in a man with headache and vertigo. Intrasinus pressure measurements revealed a significant pressure gradient across the lesion. MR imaging is useful to identify giant arachnoid granulation and dural sinus thrombosis, whereas dural sinus pressure measurement in certain cases of giant arachnoid granulations can be used to evaluate the lesion as the cause of the patient's symptoms. (orig.)

  8. Giant arachnoid granulation in a patient with benign intracranial hypertension

    Energy Technology Data Exchange (ETDEWEB)

    Kiroglu, Yilmaz; Yaqci, Baki; Cirak, Bayram; Karabulut, Nevzat [Pamukkale University, Department of Radiology, School of Medicine, Denizli (Turkey)

    2008-10-15

    We report magnetic resonance (MR), computed tomography (CT) and angiographic imaging of an unusual giant arachnoid granulation in the superior sagittal sinus in a man with headache and vertigo. Intrasinus pressure measurements revealed a significant pressure gradient across the lesion. MR imaging is useful to identify giant arachnoid granulation and dural sinus thrombosis, whereas dural sinus pressure measurement in certain cases of giant arachnoid granulations can be used to evaluate the lesion as the cause of the patient's symptoms. (orig.)

  9. Microbial granulation for lactic acid production.

    Science.gov (United States)

    Kim, Dong-Hoon; Lee, Mo-Kwon; Hwang, Yuhoon; Im, Wan-Taek; Yun, Yeo-Myeong; Park, Chul; Kim, Mi-Sun

    2016-01-01

    This work investigated the formation of microbial granules to boost the productivity of lactic acid (LA). The flocculated form of LA-producing microbial consortium, dominated by Lactobacillus sp. (91.5% of total sequence), was initially obtained in a continuous stirred-tank reactor (CSTR), which was fed with 2% glucose and operated at a hydraulic retention time (HRT) of 12 h and pH 5.0 ± 0.1 under a thermophilic condition (50°C). The mixed liquor in the CSTR was then transferred to an up-flow anaerobic sludge blanket reactor (UASB). The fermentation performance and granulation process were monitored with a gradual decrease of HRT from 8.0 to 0.17 h, corresponding to an increase in the substrate loading from 60 to 2,880 g glucose L(-1) d(-1) . As the operation continued, the accumulation of biomass in the UASB was clearly observed, which changed from flocculent to granular form with decrease in HRT. Up to the HRT decrease to 0.5 h, the LA concentration was maintained at 19-20 g L(-1) with over 90% of substrate removal efficiency. However, further decrease of HRT resulted in a decrease of LA concentration with increase in residual glucose. Nevertheless, the volumetric LA productivity continuously increased, reaching 67 g L-fermenter (-1) h(-1) at HRT 0.17 h. The size of LA-producing granules and hydrophobicity gradually increased with decrease in HRT, reaching 6.0 mm and 60%, respectively. These biogranules were also found to have high settling velocities and low porosities, ranging 2.69-4.73 cm s(-1) and 0.39-0.92, respectively. © 2015 Wiley Periodicals, Inc.

  10. Protein-losing enteropathy in a dog with lymphangiectasia, lymphoplasmacytic enteritis and pancreatic exocrine insufficiency.

    Science.gov (United States)

    Rodríguez-Alarcón, C A; Beristaín-Ruiz, D M; Pérez-Casio, F; Rivera, R; Ochoa, G; Martín-Orozco, U

    2012-01-01

    This is a report of seven-year-old male Akita mixed dog, with protein-losing enteropathy (PLE). He had a history of chronic vomiting and diarrhea with anorexia/hyporexia. Previously he suffered acute abdomen about eight months prior to this visit. Our dog showed uncommon combination of diseases that could cause PLE since it was affected by inflammatory bowel disease (IBD), intestinal lymphangiectasia (IL), and exocrine pancreatic insufficiency (EPI). The dog had most of the abnormalities found in IL, as well as hypoalbuminemia, hyperglobulinemia, lymphopenia, hypocalcemia, and hypercholesterolemia. During endoscopy exam, we found changes characteristic of IL such as irregular small white spots. We took biopsies from stomach, duodenum, and cecum. These biopsies showed infiltration by lymphocytes and plasmatic cells in the lamina propria also, the duodenal biopsies showed moderate dilation of the lymphatic vessels. The patient had 2.1 µg/mL of TLI, this result was compatible with EPI. We assume that the first pathology in this animal was IBD, which caused chronic pancreatitis (CP) that in turn progressed to EPI. It is also possible that IL was secondary to IBD. We have reported for the first time the correlation of IBD and EPI in dogs. This should change our approach to treating chronic diarrhea in dogs. Therefore, we propose that dogs diagnosed with EPI should also be subjected to endoscopy and intestinal biopsy. Similarly, to rule out secondary EPI, TLI should be measured routinely in dogs with IBD.

  11. Effect of long-term administration of dietary fiber on the exocrine pancreas in the rat.

    Science.gov (United States)

    Sommer, H; Kasper, H

    1984-08-01

    Male Sprague-Dawley rats (50--70g) were fed a standard laboratory diet containing 6% dietary fiber substances (diet I), the same diet supplemented with 5% guar (diet II), 10% wheat bran (diet III), or 5% pectin of high (76%) methylic esterification (diet IV), or a fiber-free diet (diet V). After a 6-week feeding period, the body weight of the animals had increased to 300--350g. The common bile duct was then canulated and the exocrine pancreatic function tested under urethane anesthesia (1.5 g/kg body weight). The tested fiber substances had no effect on the basal pancreatic secretion of volume, bicarbonate, lipase, amylase or protein, or on the wet weight and histological appearance of the organ. However, the fiber substances influenced the pancreatic response to maximal exogenous stimulation with secretin (3.0 CU/100 g X hour) and cholecystokinin (0.6 IDU/100 g X hour) and the enzyme content of the gland significantly. Compared with diet V, diet I increased the DNA content of the pancreas and its secretion of bicarbonate and protein, and decreased the protein concentration in the gland. Diet II reduced the pancreatic content of trypsinogen and protein. Diet III decreased the protein content, but increased the bicarbonate secretion, which was also increased by diet IV. -- We conclude that fiber substances influence stimulated secretion and the enzyme content of the pancrease to a varying degree.

  12. Monitoring the effect of substitution therapy in patients with exocrine pancreatic insufficiency

    Energy Technology Data Exchange (ETDEWEB)

    Joergensen, B.B. (Glostrup Hospital (Denmark)); Pedersen, N.T.; Worning, H. (Central Hospital, Herning (Denmark))

    1991-01-01

    Twenty-three outpatients with chronic pancreatitis and severe exocrine insufficiency were studied for the purpose of comparing the effect of Pancrease, Pankreon and Pankreatin by estimation of duodenal enzyme activity, the faecal fat excretion, and the faecal {sup 14}C-triolein-{sup 3}H-oleic acid test and, at the same time, to evaluate these tests when monitoring outpatients. The three preparations did not disclose any significant difference in treating steatorrhoea. Pankreatin increased the meal-stimulated duodenal enzyme activity (p<0.01) and caused reduction in the faecal fat excretion (p<0.05), whereas no change in these variables were observed with Pankreon or Pancrease. The faecal {sup 14}-C-triolein-{sup 3}H-oleic acid test showed significant improvement in the {sup 14}C-triolein digestion with all three preparations (p<0.001). The faecal {sup 14}-C-triolein-{sup 3}H-oleic acid test was the most reliable when monitoring outpatients. 17 refs., 1 fig., 3 tabs.

  13. Starch Origin and Thermal Processing Affect Starch Digestion in a Minipig Model of Pancreatic Exocrine Insufficiency.

    Science.gov (United States)

    Mößeler, Anne; Vagt, Sandra; Beyerbach, Martin; Kamphues, Josef

    2015-01-01

    Although steatorrhea is the most obvious symptom of pancreatic exocrine insufficiency (PEI), enzymatic digestion of protein and starch is also impaired. Low praecaecal digestibility of starch causes a forced microbial fermentation accounting for energy losses and meteorism. To optimise dietetic measures, knowledge of praecaecal digestibility of starch is needed but such information from PEI patients is rare. Minipigs fitted with an ileocaecal fistula with (n = 3) or without (n = 3) pancreatic duct ligation (PL) were used to estimate the rate of praecaecal disappearance (pcD) of starch. Different botanical sources of starch (rice, amaranth, potato, and pea) were fed either raw or cooked. In the controls (C), there was an almost complete pcD (>92%) except for potato starch (61.5%) which was significantly lower. In PL pcD of raw starch was significantly lower for all sources of starch except for amaranth (87.9%). Thermal processing increased pcD in PL, reaching values of C for starch from rice, potato, and pea. This study clearly underlines the need for precise specification of starch used for patients with specific dietetic needs like PEI. Data should be generated in suitable animal models or patients as tests in healthy individuals would not have given similar conclusions.

  14. Starch Origin and Thermal Processing Affect Starch Digestion in a Minipig Model of Pancreatic Exocrine Insufficiency

    Directory of Open Access Journals (Sweden)

    Anne Mößeler

    2015-01-01

    Full Text Available Although steatorrhea is the most obvious symptom of pancreatic exocrine insufficiency (PEI, enzymatic digestion of protein and starch is also impaired. Low praecaecal digestibility of starch causes a forced microbial fermentation accounting for energy losses and meteorism. To optimise dietetic measures, knowledge of praecaecal digestibility of starch is needed but such information from PEI patients is rare. Minipigs fitted with an ileocaecal fistula with (n=3 or without (n=3 pancreatic duct ligation (PL were used to estimate the rate of praecaecal disappearance (pcD of starch. Different botanical sources of starch (rice, amaranth, potato, and pea were fed either raw or cooked. In the controls (C, there was an almost complete pcD (>92% except for potato starch (61.5% which was significantly lower. In PL pcD of raw starch was significantly lower for all sources of starch except for amaranth (87.9%. Thermal processing increased pcD in PL, reaching values of C for starch from rice, potato, and pea. This study clearly underlines the need for precise specification of starch used for patients with specific dietetic needs like PEI. Data should be generated in suitable animal models or patients as tests in healthy individuals would not have given similar conclusions.

  15. VIP and its homologous increase vascular conductance in certain endocrine and exocrine glands

    International Nuclear Information System (INIS)

    Huffman, L.J.; Connors, J.M.; Hedge, G.A.

    1988-01-01

    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 141 Ce-labeled microspheres. Circulating thyrotropin (TSH), triiodothyronine (T 3 ), and thyroxine (T 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 3 , and T 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

  16. Excess influx of Zn(2+) into dentate granule cells affects object recognition memory via attenuated LTP.

    Science.gov (United States)

    Suzuki, Miki; Fujise, Yuki; Tsuchiya, Yuka; Tamano, Haruna; Takeda, Atsushi

    2015-08-01

    The influx of extracellular Zn(2+) into dentate granule cells is nonessential for dentate gyrus long-term potentiation (LTP) and the physiological significance of extracellular Zn(2+) dynamics is unknown in the dentate gyrus. Excess increase in extracellular Zn(2+) in the hippocampal CA1, which is induced with excitation of zincergic neurons, induces memory deficit via excess influx of Zn(2+) into CA1 pyramidal cells. In the present study, it was examined whether extracellular Zn(2+) induces object recognition memory deficit via excess influx of Zn(2+) into dentate granule cells. KCl (100 mM, 2 µl) was locally injected into the dentate gyrus. The increase in intracellular Zn(2+) in dentate granule cells induced with high K(+) was blocked by co-injection of CaEDTA and CNQX, an extracellular Zn(2+) chelator and an AMPA receptor antagonist, respectively, suggesting that high K(+) increases the influx of Zn(2+) into dentate granule cells via AMPA receptor activation. Dentate gyrus LTP induction was attenuated 1 h after KCl injection into the dentate gyrus and also attenuated when KCl was injected 5 min after the induction. Memory deficit was induced when training of object recognition test was performed 1 h after KCl injection into the dentate gyrus and also induced when KCl was injected 5 min after the training. High K(+)-induced impairments of LTP and memory were rescued by co-injection of CaEDTA. These results indicate that excess influx of Zn(2+) into dentate granule cells via AMPA receptor activation affects object recognition memory via attenuated LTP induction. Even in the dentate gyrus where is scarcely innervated by zincergic neurons, it is likely that extracellular Zn(2+) homeostasis is strictly regulated for cognition. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. A low-density culture method of cerebellar granule neurons with paracrine support applicable for the study of neuronal morphogenesis.

    Science.gov (United States)

    Kubota, Kenta; Seno, Takeshi; Konishi, Yoshiyuki

    2013-11-20

    Cerebellar granule neuronal cultures have been used to study the molecular mechanisms underlying neuronal functions, including neuronal morphogenesis. However, a limitation of this system is the difficulty to analyze isolated neurons because these are required to be maintained at a high density. Therefore, in the present study, we aimed to develop a simple and cost-effective method for culturing low-density cerebellar granule neurons. Cerebellar granule cells at two different densities (low- and high-density) were co-cultivated in order for the low-density culture to be supported by the paracrine signals from the high-density culture. This method enabled morphology analysis of isolated cerebellar granule neurons without astrocytic feeder cultures or supplements such as B27. Using this method, we investigated the function of a polarity factor. Studies using hippocampal neurons suggested that glycogen synthase kinase-3 (GSK-3) is an essential regulator of neuronal polarity, and inhibition of GSK-3 results in the formation of multiple axons. Pharmacological inhibitors for GSK-3 (6-bromoindirubin-3'-oxime and lithium chloride) did not cause the formation of multiple axons of cerebellar granule neurons but significantly reduced their length. Consistent results were obtained by introducing kinase-dead form of GSK-3 beta (K85A). These results indicated that GSK-3 is not directly involved in the control of neuronal polarity in cerebellar granule neurons. Overall, this study provides a simple method for culturing low-density cerebellar granule neurons and insights in to the neuronal-type dependent function of GSK-3 in neuronal morphogenesis. © 2013 Elsevier B.V. All rights reserved.

  18. New developments on transition radiation detectors using superconducting granules

    International Nuclear Information System (INIS)

    Yuan, L.C.L.

    1977-01-01

    By raising slightly either the temperature or the magnetic field to above that of the critical temperature or the critical magnetic field, the type I superconducting granules would still remain in the superconducting state which becomes a metastable state and is called the superheated superconducting state. If a relativistic charged particle incident on such a granule which is located in a colloidal suspension has imported to it an energy that is above the threshold energy (for state flipping) of the granule then it would flip to the normal state. The threshold energy of a granule is a function of the square of its radius, whereas the energy loss of a charged particle due to ionization is linearly proportional to the radius. The size of the granule can be pre-determined to be such that its threshold energy is slightly above the ionization loss of a relativistic charged particle. Then the traversal of the charged particle through such a granule would not affect the superconducting state of the granule unless a transition x-ray radiation is emitted at the surface of the granule by the traversing particle and the x-ray transition radiation is immediately absorbed either in total or partially by the metallic granule causing it to flip to the normal state. The total intensity of the x-ray transition radiation is linearly proportional to the Lorentz factor γ of the traversing particle, and the number of granules flipped would also be a measure of γ. Three methods for detecting the flipping of granules from the superconducting state to the normal state are described. They include the frequency measuring method, the SQUID method, and the pulse method with low noise amplifier system

  19. Identification of Neuregulin-2 as a novel stress granule component.

    Science.gov (United States)

    Kim, Jin Ah; Jayabalan, Aravinth Kumar; Kothandan, Vinoth Kumar; Mariappan, Ramesh; Kee, Younghoon; Ohn, Takbum

    2016-08-01

    Stress Granules (SGs) are microscopically visible, phase dense aggregates of translationally stalled messenger ribonucleoprotein (mRNP) complexes formed in response to distinct stress conditions. It is generally considered that SG formation is induced to protect cells from conditions of stress. The precise constituents of SGs and the mechanism through which SGs are dynamically regulated in response to stress are not completely understood. Hence, it is important to identify proteins which regulate SG assembly and disassembly. In the present study, we report Neuregulin-2 (NRG2) as a novel component of SGs; furthermore, depletion of NRG2 potently inhibits SG formation. We also demonstrate that NRG2 specifically localizes to SGs under various stress conditions. Knockdown of NRG2 has no effect on stress-induced polysome disassembly, suggesting that the component does not influence early step of SG formation. It was also observed that reduced expression of NRG2 led to marginal increase in cell survival under arsenite-induced stress. [BMB Reports 2016; 49(8): 449-454].

  20. Metatranscriptomics reveals the molecular mechanism of large granule formation in granular anammox reactor

    KAUST Repository

    Bagchi, Samik; Lamendella, Regina; Strutt, Steven; Van Loosdrecht, Mark C. M.; Saikaly, Pascal

    2016-01-01

    to formation of large granules. Size distribution analysis revealed the spatial distribution of granules in which large granules having higher abundance of anammox bacteria (genus Brocadia) dominated the bottom biomass. Metatranscriptomics analysis detected all

  1. Granule properties of paracetamol made with Bombax ceiba gum ...

    African Journals Online (AJOL)

    Bombax ceiba gum was extracted from the calyx of the Bombax flower using both hot and cold water extraction method. The gum was used as binder to prepare paracetamol granules in concentrations of 1, 1.5, 2, and 3 %. Acacia gum was used to prepare the standard at the same concentrations. The granule properties of ...

  2. Proximate analysis of Sweet Potato Toasted Granules | Meludu ...

    African Journals Online (AJOL)

    Sweet potato is an important root crop in the food system of many African countries. The yield, nutrition and economic potential of sweet potato have been identified as very high. In this study, sweet potato was processed and toasted into granules. The proximate analysis performed on the toasted granules showed protein, ...

  3. Application of granulating of tires; Aplicaciones de granulado de NFUs

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez Justicia, A.

    2001-07-01

    At present, used tires are mainly used as fuel, retreading and granulating of tires. In this article. I will focus on the last option, talking about some of the multiple applications and going into detail of the making process of the granulation of used tires in a recycling plant. (Author)

  4. Roll compaction and granulation system for nuclear fuel material

    International Nuclear Information System (INIS)

    Goldmann, L.H. Jr.; Holley, C.C.

    1981-01-01

    A roll compaction and roll granulation system has been designed and fabricated to replace conventional preslugging and crushing operations typically used in the fabrication of mixed oxide nuclear fuel pellets. This equipment will be of maintenance advantage with only the compaction and granulation rolls inside containment. The prototype is being tested and the results will be reported within a year

  5. Nonreutilizaton of adrenal chromaffin granule membranes following secretion

    International Nuclear Information System (INIS)

    Nobiletti, J.B.

    1985-01-01

    The intracellular postexocytotic fate of the adrenal chromaffin granule membrane (reutilization vs. nonreutilization) was addressed through two experimental approaches. First, ( 3 H) leucine pulse-chase labeling experiments were conducted in two systems - the isolated retrograde perfused cat adrenal gland and cultured bovine adrenal chromaffin cells to compare chromaffin granule soluble dopamine-B-hydroxylase (DBH) turnover (marker for granule soluble content turnover) to that of membrane-bound DBH (marker for granule membrane turnover). Experiments in cat adrenal glands showed that at all chase periods the granule distribution of radiolabeled DBH was in agreement with the DBH activity distribution (73% membrane-bound/27% soluble) - a result consistent with parallel turnover of soluble and membrane-bound DBH. Experiments in cultured bovine cells showed that labeled soluble and membrane-bound DBH had parallel turnover patterns and at all chase period, the distribution of radiolabeled DBH between the soluble contents and membranes was similar to the DBH activity distribution (50% soluble/50% membrane-bound). The above experiments showed that the soluble contents and membranes turnover in parallel and are consistent with nonreutilization of chromaffin granule membranes following exocytosis. Isolated retrograde perfused bovine adrenal glands were subjected to repetitive acetylcholine stimulation to induce exocytosis and then the dense and less-dense chromaffin granule fractions were isolated. Since both approaches gave results consistent with membrane nonreutilization, the authors conclude that once a chromaffin granule is involved in exocytosis, its membrane is not reutilized for the further synthesis, storage, and secretion of catecholamines

  6. Autophagy meets fused in sarcoma-positive stress granules.

    Science.gov (United States)

    Matus, Soledad; Bosco, Daryl A; Hetz, Claudio

    2014-12-01

    Mutations in fused in sarcoma and/or translocated in liposarcoma (FUS, TLS or FUS) are linked to familial cases of amyotrophic lateral sclerosis (ALS). Mutant FUS selectively accumulates into discrete cytosolic structures known as stress granules under various stress conditions. In addition, mutant FUS expression can alter the dynamics and morphology of stress granules. Although the link between mutant FUS and stress granules is well established, the mechanisms modulating stress granule formation and disassembly in the context of ALS are poorly understood. In this issue of Neurobiology of Aging, Ryu et al. uncover the impact of autophagy on the potential toxicity of mutant FUS-positive stress granules. The authors provide evidence indicating that enhanced autophagy activity reduces the number of stress granules, which in the case of cells containing mutant FUS-positive stress granules, is neuroprotective. Overall, this study identifies an intersection between the proteostasis network and alterations in RNA metabolism in ALS through the dynamic assembly and disassembly of stress granules. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Osseous drill holes to promote granulation tissue: Radiologic appearance

    International Nuclear Information System (INIS)

    Resnik, C.S.; Reiner, B.I.; Diaconis, J.N.; Goldberg, N.H.

    1991-01-01

    Skin grafting following extensive soft-tissue loss is often delayed until adequate granulation tissue can be generated. Surgical drill holes into the marrow cavity promote development of granulation tissue. This article illustrates the radiology appearance of these drill holes in four patients. (orig.)

  8. Method for the treatment of waste water with sludge granules

    NARCIS (Netherlands)

    Van Loosdrecht, M.C.; De Kreuk, M.K.

    2004-01-01

    The invention relates to a method for the treatment of waste water comprising an organic nutrient. According to the invention, the waste water is in a first step fed to sludge granules, after the supply of the waste water to be treated the sludge granules are fluidised in the presence of an

  9. Consolidating nanoparticles in micron-sized granules using spray drying

    International Nuclear Information System (INIS)

    Lindeloev, J S; Wahlberg, M

    2011-01-01

    Suspensions of nanoparticles (SiO 2 , SiC, TiO2, CNT, Nanoclay and Hydroxyapatite) were spray dried to produce dry granulated products. The nanoparticles were consolidated in granules making them more convenient and safer to use in further processing compared to handling of nanopowders.

  10. A prospective evaluation of pancreatic exocrine function in patients with acute pancreatitis: correlation with extent of necrosis and pancreatic endocrine insufficiency.

    Science.gov (United States)

    Boreham, B; Ammori, B J

    2003-01-01

    The aim of this prospective study was to assess pancreatic exocrine function in patients recovering from a first attack of acute pancreatitis, and to evaluate its relationship to severity of attack, extent of pancreatic necrosis and severity of pancreatic endocrine insufficiency. Between December 2000 and November 2001, 23 patients were prospectively evaluated. Pancreatic exocrine function was measured by the faecal elastase-1 test and insufficiency was classified as moderately impaired or severely impaired. Pancreatic necrosis was determined by contrast-enhanced CT scan, and its extent was categorised according to Balthazar's classification. The severity of pancreatic endocrine insufficiency was categorised according to insulin dependence. Attacks were classified as mild (n = 16) or severe (n = 7) according to the Atlanta criteria. Pancreatic exocrine insufficiency was significantly more frequent in patients recovering from severe attacks than mild (n = 6, 86% vs. n = 2, 13%; p = 0.002), and in those who developed pancreatic necrosis or pseudocyst than those who did not (6 of 7 patients vs. 2 of 16 patients, and 5 of 5 patients vs. 3 of 18 patients respectively; p = 0.002). The development of exocrine insufficiency correlated strongly with the extent of pancreatic necrosis (r = -0.754, p pancreatic endocrine insufficiency (n = 4, r = -0.453, p = 0.03). Pancreatic exocrine insufficiency is a common occurrence in patients recovering from severe acute pancreatitis, and its severity correlates with the extent of pancreatic necrosis and the severity of concomitant pancreatic endocrine insufficiency. Copyright 2003 S. Karger AG, Basel and IAP

  11. KIF20A-Mediated RNA Granule Transport System Promotes the Invasiveness of Pancreatic Cancer Cells

    Directory of Open Access Journals (Sweden)

    Keisuke Taniuchi

    2014-12-01

    Full Text Available Pancreatic cancers are aggressive because they are highly invasive and highly metastatic; moreover, effective treatments for aggressive pancreatic cancers are lacking. Here, we report that the motor kinesin protein KIF20A promoted the motility and invasiveness of pancreatic cancer cells through transporting the RNA-binding protein IGF2BP3 and IGF2BP3-bound transcripts toward cell protrusions along microtubules. We previously reported that IGF2BP3 and its target transcripts are assembled into cytoplasmic stress granules of pancreatic cancer cells, and that IGF2BP3 promotes the motility and invasiveness of pancreatic cancer cells through regulation of localized translation of IGF2BP3-bound transcripts in cell protrusions. We show that knockdown of KIF20A inhibited accumulation of IGF2BP3-containing stress granules in cell protrusions and suppressed local protein expression from specific IGF2BP3-bound transcripts, ARF6 and ARHGEF4, in the protrusions. Our results provide insight into the link between regulation of KIF20A-mediated trafficking of IGF2BP3-containing stress granules and modulation of the motility and invasiveness in pancreatic cancers.

  12. EXOCRINE FUNCTION OF THE LIVER IN RATS WITH EXPOSURE TO CОRVITIN.

    Science.gov (United States)

    Vovkun, T V; Yanchuk, P I; Shtanova, L Y; Vesеlskyу, S P; Shalamaу, A S

    In acute experiments on rats with cannulated bile duct we studied the effect of Corvitin, water-soluble analogue of quercetin, on secretion of bile. Intraportal administration of the test compound at doses of 2,5; 5 and 10 mg/kg resulted in a significant increase in the volume of secreted bile by 20,9, 31,2 and 20,4%, respectively, as compared with the control. Using the method of thin layer chromatography it was established the mild stimulating effect of Corvitin on the processes of bile acids conjugation with taurine and glycine, especially when administered at a dose of 5 mg/kg. This flavonoid did not affect the concentration of glycocholic acid, however increased the content of glycochenodeoxycholic and glycodeoxycholic acids in the mixture between 15 to 35,1%. Regarding free bile acids, the concentration of cholic acid, chenodeoxycholic and deoxycholic acids in the mixture was increased significantly relative to control only after Corvitin application at dose 10 mg/ kg. In the first case – from 17,9 to 29,8%, in the second – from 25 to 65,4%. At the dose of 5 mg/kg, Corvitin significantly increased the ratio of bile cholates conjugation (maximum by 23,2%), whereas 10 mg/kg of the drug decreased this index by 27,0%. After administration of Corvitin, the hydroxylation ratio in all experimental groups differed little from the control: at the dose of 5 and 10 mg/kg this parameter decreased by 14%. Thus, Corvitin modulates exocrine function of the liver, causing an increase in bile secretion and concentration of different cholates, dose-dependently increasing or decreasing the effectiveness of multienzyme systems providing processes of bile acids conjugation in rats.

  13. Clinical usefulness of dual-label Schilling test for pancreatic exocrine function

    Energy Technology Data Exchange (ETDEWEB)

    Chen, W.L.; Morishita, R.; Eguchi, T.; Kawai, T.; Sakai, M.; Tateishi, H.; Uchino, H.

    1989-05-01

    The usefulness of the pancreatic dual-label Schilling test as an indirect test of pancreatic exocrine function was evaluated. This dual-label Schilling test was based on the difference of absorption for (58Co)cobalamin bound to hog R protein and (57Co)cobalamin bound to intrinsic factor. In this study, the test was performed in 7 normal subjects, 5 patients with pancreatectomy, 12 patients with chronic pancreatitis, 10 patients with suspicion of chronic pancreatitis, and 13 patients without chronic pancreatitis. The normal lower limit (mean -2 SD) of excretion ratio for (58Co)/(57Co) in 24-h urine was 0.68. Of the 26 patients on whom endoscopic retrograde pancreatography was performed, none of the 9 patients with normal pancreatogram, 4 of the 9 patients with mild to moderate pancreatitic changes in pancreatogram, and 7 of the 8 patients with advanced pancreatitic changes in pancreatogram showed a positive value lower than the ratio of 0.68 in this test. In 28 patients examined with the direct test of pancreatic secretory capacity, 2 of the 13 patients with normal function, 6 of the 9 patients with mild dysfunction, and 5 of the 6 patients with definite dysfunction were positive in this test. The results of the pancreatic dual-label Schilling test significantly correlated with those of a direct test of pancreatic secretory capacity and the findings of pancreatitic changes in pancreatogram (p less than 0.01, chi 2 test). The ratio for (58Co)/(57Co) correlated (r = 0.73) with the maximal bicarbonate concentration in duodenal juice of the direct test of pancreatic secretory capacity. The impairment of bicarbonate output by the pancreas may adversely affect the transfer of cobalamin from R protein to intrinsic factor.

  14. Clinical usefulness of dual-label Schilling test for pancreatic exocrine function

    International Nuclear Information System (INIS)

    Chen, W.L.; Morishita, R.; Eguchi, T.; Kawai, T.; Sakai, M.; Tateishi, H.; Uchino, H.

    1989-01-01

    The usefulness of the pancreatic dual-label Schilling test as an indirect test of pancreatic exocrine function was evaluated. This dual-label Schilling test was based on the difference of absorption for [58Co]cobalamin bound to hog R protein and [57Co]cobalamin bound to intrinsic factor. In this study, the test was performed in 7 normal subjects, 5 patients with pancreatectomy, 12 patients with chronic pancreatitis, 10 patients with suspicion of chronic pancreatitis, and 13 patients without chronic pancreatitis. The normal lower limit (mean -2 SD) of excretion ratio for [58Co]/[57Co] in 24-h urine was 0.68. Of the 26 patients on whom endoscopic retrograde pancreatography was performed, none of the 9 patients with normal pancreatogram, 4 of the 9 patients with mild to moderate pancreatitic changes in pancreatogram, and 7 of the 8 patients with advanced pancreatitic changes in pancreatogram showed a positive value lower than the ratio of 0.68 in this test. In 28 patients examined with the direct test of pancreatic secretory capacity, 2 of the 13 patients with normal function, 6 of the 9 patients with mild dysfunction, and 5 of the 6 patients with definite dysfunction were positive in this test. The results of the pancreatic dual-label Schilling test significantly correlated with those of a direct test of pancreatic secretory capacity and the findings of pancreatitic changes in pancreatogram (p less than 0.01, chi 2 test). The ratio for [58Co]/[57Co] correlated (r = 0.73) with the maximal bicarbonate concentration in duodenal juice of the direct test of pancreatic secretory capacity. The impairment of bicarbonate output by the pancreas may adversely affect the transfer of cobalamin from R protein to intrinsic factor

  15. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21(st) century.

    Science.gov (United States)

    Trang, Tony; Chan, Johanna; Graham, David Y

    2014-09-07

    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.

  16. Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21st century

    Science.gov (United States)

    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

  17. Hilar mossy cell circuitry controlling dentate granule cell excitability

    Directory of Open Access Journals (Sweden)

    Seiichiro eJinde

    2013-02-01

    Full Text Available Glutamatergic hilar mossy cells of the dentate gyrus can either excite or inhibit distant granule cells, depending on whether their direct excitatory projections to granule cells or their projections to local inhibitory interneurons dominate. However, it remains controversial whether the net effect of mossy cell loss is granule cell excitation or inhibition. Clarifying this controversy has particular relevance to temporal lobe epilepsy, which is marked by dentate granule cell hyperexcitability and extensive loss of dentate hilar mossy cells. Two diametrically opposed hypotheses have been advanced to explain this granule cell hyperexcitability – the dormant basket cell and the irritable mossy cell hypotheses. The dormant basket cell hypothesis proposes that mossy cells normally exert a net inhibitory effect on granule cells and therefore their loss causes dentate granule cell hyperexcitability. The irritable mossy cell hypothesis takes the opposite view that mossy cells normally excite granule cells and that the surviving mossy cells in epilepsy increase their activity, causing granule cell excitation. The inability to eliminate mossy cells selectively has made it difficult to test these two opposing hypotheses. To this end, we developed a transgenic toxin-mediated, mossy cell-ablation mouse line. Using these mutants, we demonstrated that the extensive elimination of hilar mossy cells causes granule cell hyperexcitability, although the mossy cell loss observed appeared insufficient to cause clinical epilepsy. In this review, we focus on this topic and also suggest that different interneuron populations may mediate mossy cell-induced translamellar lateral inhibition and intralamellar recurrent inhibition. These unique local circuits in the dentate hilar region may be centrally involved in the functional organization of the dentate gyrus.

  18. Gene Expression Responses to FUS, EWS, and TAF15 Reduction and Stress Granule Sequestration Analyses Identifies FET-Protein Non-Redundant Functions

    DEFF Research Database (Denmark)

    Blechingberg, Jenny; Luo, Yonglun; Bolund, Lars

    2012-01-01

    The FET family of proteins is composed of FUS/TLS, EWS/EWSR1, and TAF15 and possesses RNA- and DNA-binding capacities. The FET-proteins are involved in transcriptional regulation and RNA processing, and FET-gene deregulation is associated with development of cancer and protein granule formations...... in amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and trinucleotide repeat expansion diseases. We here describe a comparative characterization of FET-protein localization and gene regulatory functions. We show that FUS and TAF15 locate to cellular stress granules to a larger extend than EWS....... FET-proteins have no major importance for stress granule formation and cellular stress responses, indicating that FET-protein stress granule association most likely is a downstream response to cellular stress. Gene expression analyses showed that the cellular response towards FUS and TAF15 reduction...

  19. A review on granules initiation and development inside UASB Reactor and the main factors affecting granules formation process

    Energy Technology Data Exchange (ETDEWEB)

    Habeeb, S.A.; Latiff, Ab Aziz Bin Abdul; Daud, Zawawi Bin; Ahmad, Zulkifli Bin [Civil and Environmental Engineering, University Tun Hussein Onn Malaysia (Malaysia)

    2011-07-01

    Decades of investigations and explorations in the field of anaerobic wastewater treatment have resulted in significant indications about the role importance of sludge granules in biodegradation anaerobic process. It is believed that the development of anaerobic granules is reflecting an important role on the performance of reactor. An overview on the concept of up-flow anaerobic sludge bed (UASB) reactor operation as well as the main parts that reactor consists of is briefly explained in this paper, whereas the major theories of anaerobic granules formation are listed by related researchers. The correlations and compositions of such sludge granule have been specifically explained. It is believed that the extracellular polymer (ECP) is totally responsible of bacterial cell correlations and the formation of bacterial communities in the form of granules. In addition, the dependable factors for the performance of anaerobic granules formation process e.g. temperature, organic loading rate, pH, and alkalinity, nutrients, and cations and heavy metals have been discussed in this paper. Strong evidences proved that the process of gas production in the form of biogas is related to the methanogens activities, which are practically found in the core of granules. The aim of this review is to explore and assess the mechanisms of granules initiation and development inside UASB reactor.

  20. Joint Effects of Granule Size and Degree of Substitution on Octenylsuccinated Sweet Potato Starch Granules As Pickering Emulsion Stabilizers.

    Science.gov (United States)

    Li, Jinfeng; Ye, Fayin; Lei, Lin; Zhou, Yun; Zhao, Guohua

    2018-05-02

    The granules of sweet potato starch were size fractionated into three portions with significantly different median diameters ( D 50 ) of 6.67 (small-sized), 11.54 (medium-sized), and 16.96 μm (large-sized), respectively. Each portion was hydrophobized at the mass-based degrees of substitution (DS m ) of approximately 0.0095 (low), 0.0160 (medium), and 0.0230 (high). The Pickering emulsion-stabilizing capacities of modified granules were tested, and the resultant emulsions were characterized. The joint effects of granule size and DS m on emulsifying capacity (EC) were investigated by response surface methodology. For small-, medium-, and large-sized fractions, their highest emulsifying capacities are comparable but, respectively, encountered at high (0.0225), medium (0.0158), and low (0.0095) DS m levels. The emulsion droplet size increased with granule size, and the number of freely scattered granules in emulsions decreased with DS m . In addition, the term of surface density of the octenyl succinic group (SD -OSG ) was first proposed for modified starch granules, and it was proved better than DS m in interpreting the emulsifying capacities of starch granules with varying sizes. The present results implied that, as the particulate stabilizers, the optimal DS m of modified starch granules is size specific.

  1. High-shear granulation as a manufacturing method for cocrystal granules

    DEFF Research Database (Denmark)

    Rehder, Sönke; Christensen, Niels Peter Aae; Rantanen, Jukka

    2013-01-01

    and the respective excipients). The drug release was slightly decreased by cocrystal formation, most likely due to the lower solubility of the cocrystal. In the presence of calcium hydrogenphosphate however, no influence of cocrystal formation on either compactability or on drug release were observed, compared...... with the reference tablets. It was concluded that high-shear wet granulation is a valuable, however complex, manufacturing method for cocrystals. Cocrystal formation may influence compactability and drug release and thus affect drug performance and should be investigated during pre-formulation.......Cocrystal formation allows the tailoring of physicochemical as well as of mechanical properties of an API. However, there is a lack of large-scale manufacturing methods of cocrystals. Therefore, the objective of this work was to examine the suitability of high-shear wet granulation...

  2. RNA Binding Proteins in Eye Development and Disease: Implication of Conserved RNA Granule Components

    Science.gov (United States)

    Dash, Soma; Siddam, Archana D.; Barnum, Carrie E.; Janga, Sarath Chandra

    2016-01-01

    The molecular biology of metazoan eye development is an area of intense investigation. These efforts have led to the surprising recognition that although insect and vertebrate eyes have dramatically different structures, the orthologs or family members of several conserved transcription and signaling regulators such as Pax6, Six3, Prox1 and Bmp4 are commonly required for their development. In contrast, our understanding of post-transcriptional regulation in eye development and disease, particularly regarding the function of RNA binding proteins (RBPs), is limited. We examine the present knowledge of RBPs in eye development in the insect model Drosophila, as well as several vertebrate models such as fish, frog, chicken and mouse. Interestingly, of the 42 RBPs that have been investigated with for their expression or function in vertebrate eye development, 24 (~60%) are recognized in eukaryotic cells as components of RNA granules such as Processing bodies (P-bodies), Stress granules, or other specialized ribonucleoprotein (RNP) complexes. We discuss the distinct developmental and cellular events that may necessitate potential RBP/RNA granule-associated RNA regulon models to facilitate post-transcriptional control of gene expression in eye morphogenesis. In support of these hypotheses, three RBPs and RNP/RNA granule components Tdrd7, Caprin2 and Stau2 are linked to ocular developmental defects such as congenital cataract, Peters anomaly and microphthalmia in human patients or animal models. We conclude by discussing the utility of interdisciplinary approaches such as the bioinformatics tool iSyTE (integrated Systems Tool for Eye gene discovery) to prioritize RBPs for deriving post-transcriptional regulatory networks in eye development and disease. PMID:27133484

  3. The Solar-flux Third Granulation Signature

    Science.gov (United States)

    Gray, David F.; Oostra, Benjamin

    2018-01-01

    The velocity shifts of spectral lines as a function of line strength, so-called the third signature of granulation, are investigated using three published solar-flux atlases. We use flux atlases because we wish to treat the Sun as a star, against which stellar observations can be compared and judged. The atlases are critiqued and compared to the lower-resolution observations taken with the Elginfield stellar spectrograph. Third-signature plots are constructed for the 6020–6340 Å region. No dependence on excitation potential or wavelength is found over this wavelength span. The shape of the plots from the three solar atlases is essentially the same, with rms line-core velocity differences of 30–35 m s‑1. High-resolution atlas data are degraded to the level of the Elginfield spectrograph and compared to direct observations taken with that spectrograph. The line-core velocities show good agreement, with rms differences of 38 m s‑1. A new standard curve is derived and compared with the previously published one. Only small differences in shape are found, but a significant (+97 m s‑1) change in the zero point is indicated. The bisector of the Fe I 6253 line is mapped onto the third-signature plots and flux deficits are derived, which measure the granule/lane flux imbalance. The lower spectral resolution lowers the flux deficit area slightly and moves the peak of the deficit 0.3–0.5 km s‑1 toward higher velocities. These differences, while significant, are not large compared to measurement errors for stellar data.

  4. Ocular Injury due to Potassium Permanganate Granules

    Directory of Open Access Journals (Sweden)

    Chareenun Chirapapaisan

    2018-02-01

    Full Text Available Purpose: We report a rare case of ocular injury due to potassium permanganate (KMnO4 granules in a child. Methods: This is a retrospective case report. Results: A 2-year-old boy was transferred to our emergency room with severe pain in his right eye, inflamed eyelids, and brownish stains on his fingers. Chemical injury was suspected. Copious eye irrigation was immediately performed. Diffuse brownish splotches were then observed at the inferior bulbar conjunctiva. Otherwise, systemic organs were intact. Complete eye exam under general anesthesia revealed a 5-mm epithelial defect at the central cornea, along with generalized conjunctival injection and limbal ischemia, inferiorly. Multiple semi-dissolved granules of KMnO4 trapped in the inferior fornix were identified. The chemical particles were gradually washed out and removed; however, the brownish stains remained. The patient received preservative-free steroid, antibiotic eye drops, and lubricants as regular management for mild to moderate degree of ocular burn. Pseudomembrane developed early and transformed into symblepharon within a few days after the injury. Membrane adhesion was lysed, and more aggressive medications were then substituted. Commercial amniotic membrane (PROKERA® was also applied to promote wound healing and to prevent recurrence of symblepharon. The ocular surface was eventually restored, and corneal transparency was preserved. Conclusion: Ocular injury with the granular form of KMnO4 is rare. Its toxicity is comparable to concentrated KMnO4 solution. However, the dissolved particles that had been absorbed in the stained conjunctiva were continuously released and damaged the ocular surface more than we primarily anticipated. Awareness of this condition and prompt management yield a good treatment outcome.

  5. Giessen international workshop on interactions of exocrine and endocrine pancreatic diseases. Castle of Rauischholzhausen of the Justus-Liebig-University, Giessen, Germany. March 18-19, 2005.

    Science.gov (United States)

    Andren-Sandberg, Ake; Hardt, Philip D

    2005-07-08

    The 'Giessen International Workshop on Interactions of Exocrine and Endocrine Pancreatic Diseases' was held on March 18-19, 2005 at the Castle of Rauischolzhausen, Giessen University, Germany. About 50 international clinicians and researchers attended the workshop. It was structured into three sessions: A: Pancreatic Autoimmunity - Interaction Between Exocrine and Endocrine Tissue; B: Diabetes Mellitus - Possible Implications of Exocrine Pancreatic Insufficiency; C: Chronic Pancreatitis - Update on Prevalence, Understanding and Pathophysiological Concepts. Several new aspects of pancreatic diseases were discussed, including new classifications of pancreatitis, new insights into prevalence, pathophysiology and new therapeutical considerations. The meeting resulted in more cooperation and a number of new concepts for clinical study which will provide data for future developments.

  6. Inhibin : its role in the regulation of the pituitary-testis axis.

    NARCIS (Netherlands)

    A.M. Ultee-van Gessel (Annemarie)

    1988-01-01

    textabstractThe endocrine and exocrine functions of the male gonads, the testes, are regulated by gonadotrophic hormones which are secreted by the pituitary gland. Two separate gonadotrophic hormones have been recognized: luteinizing hormone (LH) which influences Leydig cell function, and

  7. Comparison of 72-hour fecal fat quantification and the 13C-mixed triglyceride breath test in assessing pancreatic exocrine sufficiency in children with chronic pancreatitis.

    Science.gov (United States)

    Wejnarska, Karolina; Kołodziejczyk, Elwira; Ryżko, Józef; Oracz, Grzegorz

    Chronic pancreatitis (CP) in children is still a rare, although increasingly recognized entity. Over the duration of the disease several complications can be observed, two of which are major ones: endo- and exocrine insufficiency. In the medical care of children with CP it is crucial to diagnose the decreased endo- and exocrine function of the pancreas, in order to preserve patients from malnutrition and the failure to thrive. The aim of the study was to compare the usefulness of two indirect methods of assessing the pancreas exocrine function in children with CP. Ninety one patients with CP were enrolled in the study (41 boys, 50 girls, aged 2-17.8 years). Only Patients who had had both the 72-hour fecal fat quantification and the 13C-mixed triglyceride breath test (13C -MTBT) performed were selected. We compared the results of both tests for sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) in detecting exocrine pancreatic insufficiency. Out of 91 patients, 12 were diagnosed with exocrine pancreatic insufficiency (EPI). The sensitivity of the fecal fat quantification was 50%, the specificity for the test was 100%. PPV and NPV were 100% and 93%, respectively. 13C-MTBT had the sensitivity of 42% and the specificity of 99%. PPV and NPV for the breath test were of 83% and 92%, respectively. No statistically significant discrepancy between the values obtained was found. Although the 72-hour fecal fat quantification remains the gold standard in detecting EPI, both of the methods that had been investigated were shown to be comparable regarding sensitivity, specificity, PPV and NPV in assessing pancreas exocrine sufficiency in children with CP. Due to the easier execution of the breath test, both for the patient and for medical personnel, its importance may increase.

  8. UNCERTAINTY HANDLING IN DISASTER MANAGEMENT USING HIERARCHICAL ROUGH SET GRANULATION

    Directory of Open Access Journals (Sweden)

    H. Sheikhian

    2015-08-01

    Full Text Available Uncertainty is one of the main concerns in geospatial data analysis. It affects different parts of decision making based on such data. In this paper, a new methodology to handle uncertainty for multi-criteria decision making problems is proposed. It integrates hierarchical rough granulation and rule extraction to build an accurate classifier. Rough granulation provides information granules with a detailed quality assessment. The granules are the basis for the rule extraction in granular computing, which applies quality measures on the rules to obtain the best set of classification rules. The proposed methodology is applied to assess seismic physical vulnerability in Tehran. Six effective criteria reflecting building age, height and material, topographic slope and earthquake intensity of the North Tehran fault have been tested. The criteria were discretized and the data set was granulated using a hierarchical rough method, where the best describing granules are determined according to the quality measures. The granules are fed into the granular computing algorithm resulting in classification rules that provide the highest prediction quality. This detailed uncertainty management resulted in 84% accuracy in prediction in a training data set. It was applied next to the whole study area to obtain the seismic vulnerability map of Tehran. A sensitivity analysis proved that earthquake intensity is the most effective criterion in the seismic vulnerability assessment of Tehran.

  9. Assessment of physical properties of granules with paracetamol and caffeine

    Directory of Open Access Journals (Sweden)

    Michal Szumilo

    2017-09-01

    Full Text Available Caffeine increases the analgesic properties of acetaminophen and therefore it is reasonable to use both substances together in one drug form in stronger pain. Currently, there are no commercially available pharmaceutical combination products containing acetaminophen and caffeine, which is present as granules. The aim of the study was to obtain twelve different granules with these therapeutic substances and determine the effect of various excipients on the quality of the drug form. All the granules were made by wet granulation. Two types of binders were used: polyethylene glycol 6000 (PEG and polyvinylpyrrolidone K30 (PVP as well as different types of fillers. The physical properties of granules were assessed in accordance to the requirements of the European Pharmacopoeia 8th ed. The highest apparent density was found in preparations containing calcium hydrophosphate (0.609 g/mL and the lowest – containing mannitol (0.353 g/mL as a filler. The Hausner ratio of most prepared granules ranged from 1.05 to 1.11, while the compressibility index ranged from 4.59 to 10.48%. The evaluation of properties of individual granules helped to indicate formulation with good features, which perhaps will be a good alternative to currently available painkillers with caffeine and acetaminophen.

  10. On the regulatory functions of neuropeptide Y (NPY) with respect to vascular resistance and exocrine and endocrine secretion in the pig pancreas

    DEFF Research Database (Denmark)

    Holst, J J; Orskov, C; Knuhtsen, S

    1989-01-01

    We compared the effects of electrical stimulation of the splanchnic nerves and infusions of neuropeptide Y, noradrenaline or a combination of the two on pancreatic vascular resistance and exocrine and endocrine secretion. For these studies we used isolated perfused pig pancreas with preserved...... splanchnic nerve supply. The exocrine secretion was stimulated with physiological concentrations of secretin and cholecystokinin octapeptide. Noradrenaline and NPY at 10(-8) M both increased pancreatic perfusion pressure. Their effects were additive and similar in magnitude to that of electrical stimulation...

  11. Zinc sulfide in intestinal cell granules of Ancylostoma caninum adults

    Energy Technology Data Exchange (ETDEWEB)

    Gianotti, A.J.; Clark, D.T.; Dash, J. (Portland State Univ., OR (USA))

    1991-04-01

    A source of confusion has existed since the turn of the century about the reddish brown, weakly birefringent 'sphaerocrystals' located in the intestines of strongyle nematodes, Strongylus and Ancylostoma. X-ray diffraction and energy dispersive spectrometric analyses were used for accurate determination of the crystalline order and elemental composition of the granules in the canine hookworm Ancylostoma caninum. The composition of the intestinal pigmented granules was identified unequivocally as zinc sulfide. It seems most probable that the granules serve to detoxify high levels of metallic ions (specifically zinc) present due to the large intake of host blood.

  12. Mechanistic modelling of the drying behaviour of single pharmaceutical granules

    DEFF Research Database (Denmark)

    Thérèse F.C. Mortier, Séverine; Beer, Thomas De; Gernaey, Krist

    2012-01-01

    The trend to move towards continuous production processes in pharmaceutical applications enhances the necessity to develop mechanistic models to understand and control these processes. This work focuses on the drying behaviour of a single wet granule before tabletting, using a six...... phase (submodel 2), the water inside the granule evaporates. The second submodel contains an empirical power coefficient, b. A sensitivity analysis was performed to study the influence of parameters on the moisture content of single pharmaceutical granules, which clearly points towards the importance...

  13. Stress granules at the intersection of autophagy and ALS.

    Science.gov (United States)

    Monahan, Zachary; Shewmaker, Frank; Pandey, Udai Bhan

    2016-10-15

    Amyotrophic lateral sclerosis (ALS) is a progressive, fatal disease caused by loss of upper and lower motor neurons. The majority of ALS cases are classified as sporadic (80-90%), with the remaining considered familial based on patient history. The last decade has seen a surge in the identification of ALS-causing genes - including TARDBP (TDP-43), FUS, MATR3 (Matrin-3), C9ORF72 and several others - providing important insights into the molecular pathways involved in pathogenesis. Most of the protein products of ALS-linked genes fall into two functional categories: RNA-binding/homeostasis and protein-quality control (i.e. autophagy and proteasome). The RNA-binding proteins tend to be aggregation-prone with low-complexity domains similar to the prion-forming domains of yeast. Many also incorporate into stress granules (SGs), which are cytoplasmic ribonucleoprotein complexes that form in response to cellular stress. Mutant forms of TDP-43 and FUS perturb SG dynamics, lengthening their cytoplasmic persistence. Recent evidence suggests that SGs are regulated by the autophagy pathway, suggesting a unifying connection between many of the ALS-linked genes. Persistent SGs may give rise to intractable aggregates that disrupt neuronal homeostasis, thus failure to clear SGs by autophagic processes may promote ALS pathogenesis. This article is part of a Special Issue entitled SI:Autophagy. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Calcium signalling in the acinar environment of the exocrine pancreas: physiology and pathophysiology.

    Science.gov (United States)

    Gryshchenko, Oleksiy; Gerasimenko, Julia V; Peng, Shuang; Gerasimenko, Oleg V; Petersen, Ole H

    2018-02-09

    Ca 2+ signalling in different cell types in exocrine pancreatic lobules was monitored simultaneously and signalling responses to various stimuli were directly compared. Ca 2+ signals evoked by K + -induced depolarization were recorded from pancreatic nerve cells. Nerve cell stimulation evoked Ca 2+ signals in acinar but not in stellate cells. Stellate cells are not electrically excitable as they, like acinar cells, did not generate Ca 2+ signals in response to membrane depolarization. The responsiveness of the stellate cells to bradykinin was markedly reduced in experimental alcohol-related acute pancreatitis, but they became sensitive to stimulation with trypsin. Our results provide fresh evidence for an important role of stellate cells in acute pancreatitis. They seem to be a critical element in a vicious circle promoting necrotic acinar cell death. Initial trypsin release from a few dying acinar cells generates Ca 2+ signals in the stellate cells, which then in turn damage more acinar cells causing further trypsin liberation. Physiological Ca 2+ signals in pancreatic acinar cells control fluid and enzyme secretion, whereas excessive Ca 2+ signals induced by pathological agents induce destructive processes leading to acute pancreatitis. Ca 2+ signals in the peri-acinar stellate cells may also play a role in the development of acute pancreatitis. In this study, we explored Ca 2+ signalling in the different cell types in the acinar environment of the pancreatic tissue. We have, for the first time, recorded depolarization-evoked Ca 2+ signals in pancreatic nerves and shown that whereas acinar cells receive a functional cholinergic innervation, there is no evidence for functional innervation of the stellate cells. The stellate, like the acinar, cells are not electrically excitable as they do not generate Ca 2+ signals in response to membrane depolarization. The principal agent evoking Ca 2+ signals in the stellate cells is bradykinin, but in experimental alcohol

  15. A hypothetical role for vitamin K2 in the endocrine and exocrine aspects of dental caries.

    Science.gov (United States)

    Southward, Ken

    2015-03-01

    The growing interest in oral/systemic links demand new paradigms to understand disease processes. New opportunities for dental research, particularly in the fields of neuroscience and endocrinology will emerge. The role of the hypothalamus portion of the brain cannot be underestimated. Under the influence of nutrition, it plays a significant role in the systemic model of dental caries. Currently, the traditional theory of dental caries considers only the oral environment and does not recognize any significant role for the brain. The healthy tooth, however, has a centrifugal fluid flow to nourish and cleanse it. This is moderated by the hypothalamus/parotid axis which signals the endocrine portion of the parotid glands. High sugar intake creates an increase in reactive oxygen species and oxidative stress in the hypothalamus. When this signaling mechanism halts or reverses the dentinal fluid flow, it renders the tooth vulnerable to oral bacteria, which can now attach to the tooth's surface. Acid produced by oral bacteria such as Strep Mutans and lactobacillus can now de-mineralize the enamel and irritate the dentin. The acid attack stimulates an inflammatory response which results in dentin breakdown from the body's own matrix metalloproteinases. Vitamin K2 (K2) has been shown to have an antioxidant potential in the brain and may prove to be a potent way to preserve the endocrine controlled centrifugal dentinal fluid flow. Stress, including oxidative stress, magnifies the body's inflammatory response. Sugar can not only increase oral bacterial acid production but it can concurrently reduce the tooth's defenses through endocrine signaling. Saliva production is the exocrine function of the salivary glands. The buffering capacity of saliva is critical to neutralizing the oral environment. This minimizes the de-mineralization of enamel and enhances its re-mineralization. K2, such as that found in fermented cheese, improves salivary buffering through its influence on

  16. Pancreatic exocrine insufficiency following acute pancreatitis: Systematic review and study level meta-analysis.

    Science.gov (United States)

    Hollemans, Robbert A; Hallensleben, Nora D L; Mager, David J; Kelder, Johannes C; Besselink, Marc G; Bruno, Marco J; Verdonk, Robert C; van Santvoort, Hjalmar C

    2018-04-01

    This study systematically explores the prevalence of pancreatic exocrine insufficiency (PEI) after acute pancreatitis in different subgroups of etiology (biliary/alcoholic/other), disease severity and follow-up time ( 36 months after index admission). PubMed and EMBASE databases were searched, 32 studies were included in this study level meta-analysis. In a total of 1495 patients with acute pancreatitis, tested at a mean of 36 months after index admission, the pooled prevalence of PEI was 27.1% (95%-confidence interval [CI]: 20.3%-35.1%). Patients from seven studies (n = 194) underwent direct tests with pooled prevalence of 41.7% [18.5%-69.2%]. Patients from 26 studies (n = 1305) underwent indirect tests with pooled prevalence of 24.4% [18.3%-31.8%]. In subgroup analyses on patients that underwent fecal elastase-1 tests, PEI occurred more often in alcoholic pancreatitis (22.7% [16.6%-30.1%]) than in biliary pancreatitis (10.2% [6.2%-16.4%]) or other etiology (13.4% [7.7%-22.4%]; P = 0.02). Pooled prevalence of PEI after mild and severe pancreatitis was 19.4% [8.6%-38.2%] and 33.4% [22.6%-46.3%] respectively in studies using fecal elaste-1 tests (P = 0.049). Similar results were seen in patients without (18.9% [9.3%-34.6%]) and with necrotizing pancreatitis (32.0% [18.2%-49.8%]; P = 0.053). Over time, the prevalence of PEI decreased in patients who underwent the fecal elastase-1 test and increased in patients who underwent the fecal fat analysis. After acute pancreatitis, a quarter of all patients develop PEI during follow-up. Alcoholic etiology and severe and necrotizing pancreatitis are associated with higher risk of PEI. The prevalence of PEI may change as time of follow-up increases. Copyright © 2018 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  17. A link between interferon and augmented plasmin generation in exocrine gland damage in Sjögren's syndrome.

    Science.gov (United States)

    Gliozzi, Maria; Greenwell-Wild, Teresa; Jin, Wenwen; Moutsopoulos, Niki M; Kapsogeorgou, Efstathia; Moutsopoulos, Haralampos M; Wahl, Sharon M

    2013-02-01

    Sjögren's syndrome is an autoimmune disease that targets exocrine glands, but often exhibits systemic manifestations. Infiltration of the salivary and lacrimal glands by lymphoid and myeloid cells orchestrates a perpetuating immune response leading to exocrine gland damage and dysfunction. Th1 and Th17 lymphocyte populations and their products recruit additional lymphocytes, including B cells, but also large numbers of macrophages, which accumulate with disease progression. In addition to cytokines, chemokines, chitinases, and lipid mediators, macrophages contribute to a proteolytic milieu, underlying tissue destruction, inappropriate repair, and compromised glandular functions. Among the proteases enhanced in this local environment are matrix metalloproteases (MMP) and plasmin, generated by plasminogen activation, dependent upon plasminogen activators, such as tissue plasminogen activator (tPA). Not previously associated with salivary gland pathology, our evidence implicates enhanced tPA in the context of inflamed salivary glands revolving around lymphocyte-mediated activation of macrophages. Tracking down the mechanism of macrophage plasmin activation, the cytokines IFNγ and to a lesser extent, IFNα, via Janus kinase (JAK) and signal transducer and activator of transcription (STAT) activation, were found to be pivotal for driving the plasmin cascade of proteolytic events culminating in perpetuation of the inflammation and tissue damage, and suggesting intervention strategies to blunt irreversible tissue destruction. Published by Elsevier Ltd.

  18. TGF-beta1 immunohistochemistry and promoter methylation in chronic renal failure rats treated with Uremic Clearance Granules.

    Directory of Open Access Journals (Sweden)

    Cheng-Bin Chen

    2010-08-01

    Full Text Available The aim of the study was the explain the mechanism related to therapeutic effects of Uremic Clearance Granules (Niaoduqing Keli in Chinese on adenine-induced Chronic Renal Failure in rats. Thirty 8-week-old male Wistar rats were selected and randomly divided in to 3 groups: Normal Control Group (NCGconsisted of 10 rats, Chronic Renal Failure Pathological Control Group (PCG 10 rats, and Uremic Clearance Granules Treatment Group (UCG 10 rats. Each rat in PCG and UCG was fed with adenine-enriched diets, containing 10 g adenine per kg food for 6 weeks. After fed with adenine, each rat in UCG was administered orally with 2 ml solution of Uremic Clearance Granules for 6 weeks. The concentration of Uremic Clearance Granules solution was 0.42 g/ml which was 10 times of human. On days 42 and 84, the serum levels of creatinine, Blood Urea Nitrogen and homocysteine were determined. The methylation of TGFbeta1 promoter was tested by methylation-specific PCR. TGF-beta1 mRNA and protein expression in rat renal cortex were analyzed by real-time RT-PCR and Immunohistochemistry. (1 Experimented on model of Chronic Renal Failure in rats, the preparation was proved to be able to reduce serum creatinine, Blood Urea Nitrogen, and homocysteine (p<0.05, improve renal function. (2 The expression of TGF-beta1 in mRNA and protein level were down-regulated. (3 TGF-beta1 promoter was demethylated at some loci in PCG, and was recovered in UCG. After treatment with Uremic Clearance Granules, the Chronic Renal Failure Wistar rat's kidney function was recovered. The recovery may be result of the remethylation of TGF-beta1 promoter and then lead to TGF-beta1 be transcripted and translated normally. The experimental study explain the molecular mechanism by which Uremic Clearance Granules treat Chronic Renal Failure.

  19. Does Thermal Granulation Drive Tephra Jets?

    Science.gov (United States)

    White, J. D.; Zimanowski, B.; Buettner, R.; Sonder, I.; Dellino, P.

    2011-12-01

    Surtseyan tephra jets, also called cypressoid or cock's tail plumes, comprise a characteristic mixture of ash with bombs travelling roughly ballistic paths that tip the individual fingers of the projecting jet. Jets of similar form but smaller scale are generated by littoral magma-water interactions, confirming the general inference that surtseyan tephra jets are a characteristic product of explosive magma-water interaction, and suggesting that magmatic volatiles play a subsidiary role, if any, in their formation. Surtseyan jets have been inferred to result from both intense fuel-coolant interactions, and from simple boiling of water entrained into rising magma, and little new information has become available to test these two positions since they were clearly developed in the 1980s. Recent experiments in which magma is poured into standing water have produced vigorous jetting of hot water as melt solidifies and undergoes extensive thermal granulation. We present high-resolution hi-speed video of these jets, which we see as having the following origin. As thermal granulation takes place, a fracture network advances into the melt/glass body, and water invading the cracks at the rate of propagation is heated nearly instantaneously. Vapor produced at the contact expands and drives outward through cooled cracks, condensing as it moves to the exterior of the magma body where it is emitted as a jet of hot water. In ocean ridge hydrothermal systems a diffuse crack network inducts cold water, which is heated and expelled in focused jets. Focusing of hot outflow in experiments is inferred to result, as suggested for ridge hydrothermal systems, from thermoelastic closure of cracks near the one(s) feeding the jet. From the cooled products of our experimental runs, we know that thermal contraction produces a network of curved cracks with modal spacing of 1-2 mm, which separate domains of unbroken glass. It is during growth of this crack network that cold water enters, is

  20. A review of monitoring methods for pharmaceutical wet granulation.

    Science.gov (United States)

    Hansuld, E M; Briens, L

    2014-09-10

    High-shear wet granulation is commonly used in the pharmaceutical industry to improve powder properties for downstream processes such as tabletting. Granule growth, however, is difficult to predict because the process is sensitive to raw material properties and operating conditions. Development of process analytical technologies is encouraged by regulatory bodies to improve process understanding and monitor quality online. The primary technologies investigated for high-shear wet granulation monitoring include power consumption, near-infrared spectroscopy, Raman spectroscopy, capacitance measurements, microwave measurements, imaging, focused beam reflectance measurements, spatial filter velocimetry, stress and vibration measurements, as well as acoustic emissions. This review summarizes relevant research related to each of these technologies and discusses the challenges associated with each approach as a possible process analytical technology tool for high-shear wet granulation. Copyright © 2014 Elsevier B.V. All rights reserved.

  1. Evaluation of Grade 120 Granulated Ground blast Furnace Slag.

    Science.gov (United States)

    1999-06-01

    This study evaluates Grade 120 Granulated Ground Blast Furnace Slag (GGBFS) and its effect on the properties of hydraulic cement concretes used in structural and pavement construction. Several mix designs, structural and pavement, were used for this ...

  2. Treatment of hyper-granulated limb wounds in horses

    Directory of Open Access Journals (Sweden)

    O. A. Bader

    2011-01-01

    Full Text Available This study was performed to investigate the different methods of treating hyper granulation tissue on experimentally induced wounds in equine limbs. Wounds were induced by removal of a skin patch and subcutaneous tissue for about 5-7 cm width and 6-8 cm in length from the dorsal and lateral aspect of the fore and hind limbs below the carpal and tarsal joints. The wounds were left open without treatment and the animals were trained 2-2.5 hours every day for about 3-5 weeks until hyper granulation tissue was developed. The schedule for the treatment of hyper granulation was divided into five groups each contained eight wounds of hyper granulation tissue; each main group was divided into two subgroups. The subgroups of first, second, third, fourth and fifth groups were treated by the following schedules: bandage alone; copper sulphate ointment 10%; silver nitrate ointment 2%; red mercury ointment 11%; and laser therapy (at a total dose of 9.72 Joule / cm2 respectively. While the second subgroups were treated by surgical resection of the hyper granulation tissue, followed by the same treatments applied on the first subgroup. The bandage for all experimental groups was changed every 48 hours until healing was occurred. The clinical and histological observation of the first group revealed that the healing take long period comparing with other groups. The mean of wound healing were 65 days in non surgical removal of hyper granulation tissue subgroup, while 57 days in surgical removed of hyper granulation tissue subgroup. The results of the second, third, fourth groups revealed that the caustic material especially red mercury has a role in healing processes through depressing the hyper granulation tissue. The mean of wound healing of the second group was 42.25 days in non surgical removal of hyper granulation tissue subgroup while 37.25 days in surgically removed hyper granulation tissue subgroup. In the third group the mean of wound healing was 45

  3. In vitro binding of puroindolines to wheat starch granules

    DEFF Research Database (Denmark)

    Sørensen, Helle Aagaard; Darlington, H.F.; Shewry, P.R.

    2001-01-01

    Puroindoline (pin) preparations made from flours of hard and soft wheats contained a mixture of pin-a, 0.19/0.53 alpha -amylase inhibitor, and purothionins. Starch granule preparations from the same cultivars were treated with proteinase to remove surface proteins and incubated with solutions...... of the pin preparations. Binding of pin-a and purothionins but not the 0.19/0.53 inhibitor was observed with no apparent differences between the behavior of the pin preparations or starch granule preparations from hard or soft types. No binding was observed when several other proteins (bovine serum albumin......, total albumins, a commercial preparation of wheat alpha -amylase inhibitors, and barley beta -amylase) were incubated with the starch granules under the same conditions, indicating that in vitro binding can be used to study specific starch granule and protein interactions....

  4. A Review of Granulation Process for Blast Furnace Slag

    Directory of Open Access Journals (Sweden)

    Yu Pengfei

    2016-01-01

    Full Text Available Molten slags of blast furnace is a second resources with great value of 1600~1 800 MJ sensible heat per ton. At present, water-quenching process plays a leading role in recovering waste heat of the molten slags. However, this method not only cost lots of water, but also recover little sensible heat and can pollute the surrounding environment. Dry granulation process, as an environmentally friendly method with high-efficiency heat recovery, have attracted widespread attentions. In this paper, the water quenching and dry granulation processes were discussed in detail. After a thorough comparative analysis of various treatment technologies, it can be concluded that centrifugal granulation affiliated with dry granulation is the optimum process, with smaller slag particle size (about 2mm, more glassy phase and higher recovery rate.

  5. Kit systems for granulated decontamination formulations

    Science.gov (United States)

    Tucker, Mark D.

    2010-07-06

    A decontamination formulation and method of making that neutralizes the adverse health effects of both chemical and biological compounds, especially chemical warfare (CW) and biological warfare (BW) agents, and toxic industrial chemicals. The formulation provides solubilizing compounds that serve to effectively render the chemical and biological compounds, particularly CW and BW compounds, susceptible to attack, and at least one reactive compound that serves to attack (and detoxify or kill) the compound. The formulation includes at least one solubilizing agent, a reactive compound, a sorbent additive, and water. A highly adsorbent sorbent additive (e.g., amorphous silica, sorbitol, mannitol, etc.) is used to "dry out" one or more liquid ingredients into a dry, free-flowing powder that has an extended shelf life, and is more convenient to handle and mix in the field. The formulation can be pre-mixed and pre-packaged as a multi-part kit system, where one or more of the parts are packaged in a powdered, granulated form for ease of handling and mixing in the field.

  6. Behavioral experience induces zif268 expression in mature granule cells but suppresses its expression in immature granule cells

    Directory of Open Access Journals (Sweden)

    Kylie A. Huckleberry

    2015-08-01

    Full Text Available Thousands of neurons are born each day in the dentate gyrus (DG, but many of these cells die before reaching maturity. Both death and survival of adult-born neurons are regulated by neuronal activity in DG. The immediate-early gene (IEG zif268 is an important mediator of these effects, as its expression is induced by neural activity and knockout of zif268 impairs survival of adult-born neurons (Veyrac et al., 2013. Despite the apparent importance of zif268 for adult neurogenesis, its behavior-induced expression has not been fully characterized in adult-born neurons. Here we characterize behavior-evoked expression of zif268 in mature and newborn dentate granule cells (DGCs. In the general granule cell population, zif268 expression peaked 1 hour after novel environment exposure and returned to baseline by 8 hours post-exposure. However, in the doublecortin-positive (DCX+ immature neurons, zif268 expression was suppressed relative to home cage for at least 8 hours post-exposure. We next determined that exposure to water maze training, an enriched environment, or a novel environment caused approximately equal suppression of zif268 expression in DCX+ cells and approximately equal activation of zif268 in the general DGC population and in 6-week-old adult-born neurons. Finally, we asked whether zif268 suppression varied as a function of age within the DCX+ population, which ranges in age from 0 to approximately 4 weeks. Novel environment exposure had no significant effect on zif268 expression in 2- or 4-week-old BrdU-labeled neurons, but it significantly suppressed zif268 expression in 3-week-old neurons. In summary, behavioral experience transiently activated expression of zif268 in mature DGCs but caused a more long-lasting suppression of zif268 expression in immature, adult-born DGCs. We hypothesize that zif268 suppression inhibits memory-related synaptic plasticity in immature DGCs or mediates learning-induced apoptosis of immature adult

  7. Development of granules from Phyllanthus niruri spray-dried extract

    Directory of Open Access Journals (Sweden)

    Tatiane Pereira de Souza

    2009-12-01

    Full Text Available The aim of this study was to develop granules from Phyllanthus niruri spray-dried extract using dry and wet granulation and to assess techniques to enable the production of granules with improved technological characteristics and yields. Granules were characterized by granulometry, reological parameters, compression and hygroscopic behavior. Independent of the granulation technique, technologically developed granules presented particle diameter, bulk and tapped densities and compressibility indexes suitable for a solid dosage form. The compression behavior showed plastic and fragmentary deformation for granules produced by the dry granulation technique and predominantly plastic deformation for wet granulation. Concerning the humidity sorption, the study showed that granules absorb less humidity than the spray-dried extract. However, granules with Eudragit® E 100 were the least hygroscopic.O objetivo deste estudo foi desenvolver grânulos de extrato Phyllantus niruri seco por aspersão e por granulação úmida e avaliar técnicas que possibilitem a produção de grânulos com características tecnológicas e rendimentos aperfeiçoados. Os grânulos foram caracterizados por granulometria, parâmetros reológicos, compressão e comportamento higroscópico. Independentemente da técnica de granulação, os grânulos tecnologicamente desenvolvidos apresentaram diâmetro de partículas, densidades aparente e compactada e índices de compressibilidade adequados para a formulação sólida. O comportamento de compressão mostrou deformação plástica e elástica para os grânulos produzidos por técnicas de granulação seca e, predominantemente, deformação plástica para a granulação úmida. Com relação à absorção da umidade, o estudo mostrou que os grânulos absorvem menos umidade do que o extrato seco por aspersão. Entretanto, os grânulos com Eudragit E 100 foram os menos higroscópicos.

  8. The stress granule protein Vgl1 and poly(A)-binding protein Pab1 are required for doxorubicin resistance in the fission yeast Schizosaccharomyces pombe

    Energy Technology Data Exchange (ETDEWEB)

    Morita, Takahiro [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, Kowakae 3-4-1, Higashi-Osaka 577-8502 (Japan); Satoh, Ryosuke [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, Kowakae 3-4-1, Higashi-Osaka 577-8502 (Japan); Japan Society for the Promotion of Science, 1-8 Chiyoda-ku, Tokyo 102-8472 (Japan); Umeda, Nanae; Kita, Ayako [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, Kowakae 3-4-1, Higashi-Osaka 577-8502 (Japan); Sugiura, Reiko, E-mail: sugiurar@phar.kindai.ac.jp [Laboratory of Molecular Pharmacogenomics, School of Pharmaceutical Sciences, Kinki University, Kowakae 3-4-1, Higashi-Osaka 577-8502 (Japan)

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer Stress granules (SGs) as a mechanism of doxorubicin tolerance. Black-Right-Pointing-Pointer We characterize the role of stress granules in doxorubicin tolerance. Black-Right-Pointing-Pointer Deletion of components of SGs enhances doxorubicin sensitivity in fission yeast. Black-Right-Pointing-Pointer Doxorubicin promotes SG formation when combined with heat shock. Black-Right-Pointing-Pointer Doxorubicin regulates stress granule assembly independent of eIF2{alpha} phosphorylation. -- Abstract: Doxorubicin is an anthracycline antibiotic widely used for chemotherapy. Although doxorubicin is effective in the treatment of several cancers, including solid tumors and leukemias, the basis of its mechanism of action is not completely understood. Here, we describe the effects of doxorubicin and its relationship with stress granules formation in the fission yeast, Schizosaccharomyces pombe. We show that disruption of genes encoding the components of stress granules, including vgl1{sup +}, which encodes a multi-KH type RNA-binding protein, and pab1{sup +}, which encodes a poly(A)-binding protein, resulted in greater sensitivity to doxorubicin than seen in wild-type cells. Disruption of the vgl1{sup +} and pab1{sup +} genes did not confer sensitivity to other anti-cancer drugs such as cisplatin, 5-fluorouracil, and paclitaxel. We also showed that doxorubicin treatment promoted stress granule formation when combined with heat shock. Notably, doxorubicin treatment did not induce hyperphosphorylation of eIF2{alpha}, suggesting that doxorubicin is involved in stress granule assembly independent of eIF2{alpha} phosphorylation. Our results demonstrate the usefulness of fission yeast for elucidating the molecular targets of doxorubicin toxicity and suggest a novel drug-resistance mechanism involving stress granule assembly.

  9. The stress granule protein Vgl1 and poly(A)-binding protein Pab1 are required for doxorubicin resistance in the fission yeast Schizosaccharomyces pombe

    International Nuclear Information System (INIS)

    Morita, Takahiro; Satoh, Ryosuke; Umeda, Nanae; Kita, Ayako; Sugiura, Reiko

    2012-01-01

    Highlights: ► Stress granules (SGs) as a mechanism of doxorubicin tolerance. ► We characterize the role of stress granules in doxorubicin tolerance. ► Deletion of components of SGs enhances doxorubicin sensitivity in fission yeast. ► Doxorubicin promotes SG formation when combined with heat shock. ► Doxorubicin regulates stress granule assembly independent of eIF2α phosphorylation. -- Abstract: Doxorubicin is an anthracycline antibiotic widely used for chemotherapy. Although doxorubicin is effective in the treatment of several cancers, including solid tumors and leukemias, the basis of its mechanism of action is not completely understood. Here, we describe the effects of doxorubicin and its relationship with stress granules formation in the fission yeast, Schizosaccharomyces pombe. We show that disruption of genes encoding the components of stress granules, including vgl1 + , which encodes a multi-KH type RNA-binding protein, and pab1 + , which encodes a poly(A)-binding protein, resulted in greater sensitivity to doxorubicin than seen in wild-type cells. Disruption of the vgl1 + and pab1 + genes did not confer sensitivity to other anti-cancer drugs such as cisplatin, 5-fluorouracil, and paclitaxel. We also showed that doxorubicin treatment promoted stress granule formation when combined with heat shock. Notably, doxorubicin treatment did not induce hyperphosphorylation of eIF2α, suggesting that doxorubicin is involved in stress granule assembly independent of eIF2α phosphorylation. Our results demonstrate the usefulness of fission yeast for elucidating the molecular targets of doxorubicin toxicity and suggest a novel drug-resistance mechanism involving stress granule assembly.

  10. Sludge granulation during anaerobic treatment of pre-hydrolysed ...

    African Journals Online (AJOL)

    An upflow anaerobic sludge bed (UASB) digester was operated at different hydraulic retention times (HRT) ranging from 26.7 h to 2.2 h, while the organic load rate (OLR) ranged from 0.9 to 7.3 kgCOD/m3·d. Sludge granulation was observed after day 150 of operation, at an HRT of 3.4 h, when small granules of less than 2 ...

  11. Superheated superconducting granules: a detector for particle physics and astrophysics

    International Nuclear Information System (INIS)

    Gonzalez-Mestres, L.; Perret-Gallix, D.

    1987-01-01

    A general introduction to superheated superconducting granules (SSG) detectors is given and some recent results on their basic properties are presented. Granules recently made by industrial producers exhibit good metastability properties and show sensitivity, better than naively expected, to photons and ionizing particles. The behaviour of SSG detectors at very low temperatures is also discussed. We finally sketch a critical review of proposed applications to the cross-disciplinary frontier between particle physics and astrophysics

  12. Effect of granular activated carbon on the aerobic granulation of sludge and its mechanism.

    Science.gov (United States)

    Tao, Jia; Qin, Lian; Liu, Xiaoying; Li, Bolin; Chen, Junnan; You, Juan; Shen, Yitian; Chen, Xiaoguo

    2017-07-01

    The granulation of activated sludge and effect of granular activated carbon (GAC) was investigated under the alternative anaerobic and aerobic conditions. The results showed that GAC accelerated the granulation, but had no obvious effect on the bacterial community structure of granules. The whole granulation process could be categorized into three phases, i.e. lag, granulation and granule maturation phase. During lag period GAC provided nuclei for sludge to attach, and thus enhanced the morphological regularization of sludge. During granulation period the granule size increased significantly due to the growth of bacteria in granules. GAC reduced the compression caused by the inter-particle collisions and thus accelerate the granulation. GAC has no negative effect on the performance of SBR, and thus efficient simultaneous removal of COD, nitrogen and phosphorus were obtained during most of the operating time. Copyright © 2017. Published by Elsevier Ltd.

  13. Incorporation of a circulating protein into megakaryocyte and platelet granules

    Science.gov (United States)

    Handagama, P. J.; George, J. N.; Shuman, M. A.; McEver, R. P.; Bainton, D. F.

    1987-01-01

    To determine whether or not proteins circulating in plasma can be incorporated into megakaryocytes and platelets, horseradish peroxidase (HRP) was injected intravenously into guinea pigs and these cells were examined for its uptake by electron microscopy and cytochemistry. Enriched samples of megakaryocytes enabled ultrastructural analysis of large numbers of these rare cells. In megakaryocytes, 50% of alpha granules contained HRP between 75 min and 7 hr after injection. At 24 hr, 25% of the megakaryocyte granules were peroxidase-positive, less were positive by 48 hr, and there were none at 4 days. Thus, the findings demonstrate that a circulating protein can be endocytosed by megakaryocytes and rapidly packaged into alpha granules. Platelet granules also contain HRP by 7 hr after injection, and they can secrete it in response to thrombin. Unfortunately, our present studies do not allow us to distinguish between direct endocytosis by the platelet and/or shedding of new platelets from recently labeled megakaryocytes. It is concluded that while some alpha granule proteins are synthesized by megakaryocytes, others may be acquired from plasma by endocytosis. In addition to providing evidence that some of the proteins of alpha granules may be of exogenous origin, this study has allowed the definition of a pathway whereby plasma proteins may be temporarily sequestered in megakaryocytes before reentering the circulation in platelets.

  14. New Onset of Diabetes and Pancreatic Exocrine Insufficiency After Pancreaticoduodenectomy for Benign and Malignant Tumors: A Systematic Review and Meta-analysis of Long-term Results.

    Science.gov (United States)

    Beger, Hans G; Poch, Bertram; Mayer, Benjamin; Siech, Marco

    2018-02-01

    The aim of this study was to assess the frequency and severity of new onset of diabetes mellitus (NODM) and pancreatic exocrine insufficiency (PEI) after pancreaticoduodenectomy (PD) for benign and malignant tumors. When PD is performed on patients for benign tumors, the question of long-term metabolic dysfunctions becomes of importance. Medline/PubMed, Embase, and Cochrane Library were searched for articles reporting results of measuring endocrine and exocrine pancreatic functions after PD. The methodological quality of 19 studies was assessed by means of the Newcastle-Ottawa scale and Moga-Score. The mean weighted overall percentages of NODM and PEI after PD were calculated with a 95% confidence interval (CI). Of 1295 patients, data valid-for-efficacy-analysis are based on 845 patients measuring pancreatic endocrine and on 964 patients determining exocrine functions after PD. The cumulative incidence of NODM was 40 of 275 patients (14.5%; 95% CI: 10.3-18.7) in the benign tumor group, 25 of 161 (15.5%; 95% CI: 9.9-21.2) in the malignant tumor group, and 91 of 409 patients (22.2%; 95% CI: 18.2-26.3) in the benign and malignant tumor group. Comparing the frequency of NODM after PD revealed significant differences between the groups (benign vs benign and malignant P benign and malignant P benign and malignant tumors and a significant decrease of exocrine functions contribute to a rational weighting of metabolic long-term risks following PD.

  15. PHYSICAL PROPERTIES OF LARGE AND SMALL GRANULES IN SOLAR QUIET REGIONS

    Energy Technology Data Exchange (ETDEWEB)

    Yu Daren; Xie Zongxia; Hu Qinghua [Harbin Institute of Technology, Harbin 150001 (China); Yang Shuhong; Zhang Jun; Wang Jingxiu, E-mail: caddiexie@hotmail.com, E-mail: zjun@ourstar.bao.ac.cn [Key Laboratory of Solar Activity, National Astronomical Observatories, Chinese Academy of Sciences, Beijing 100012 (China)

    2011-12-10

    The normal mode observations of seven quiet regions obtained by the Hinode spacecraft are analyzed to study the physical properties of granules. An artificial intelligence technique is introduced to automatically find the spatial distribution of granules in feature spaces. In this work, we investigate the dependence of granular continuum intensity, mean Doppler velocity, and magnetic fields on granular diameter. We recognized 71,538 granules by an automatic segmentation technique and then extracted five properties: diameter, continuum intensity, Doppler velocity, and longitudinal and transverse magnetic flux density to describe the granules. To automatically explore the intrinsic structures of the granules in the five-dimensional parameter space, the X-means clustering algorithm and one-rule classifier are introduced to define the rules for classifying the granules. It is found that diameter is a dominating parameter in classifying the granules and two families of granules are derived: small granules with diameters smaller than 1.''44, and large granules with diameters larger than 1.''44. Based on statistical analysis of the detected granules, the following results are derived: (1) the averages of diameter, continuum intensity, and Doppler velocity in the upward direction of large granules are larger than those of small granules; (2) the averages of absolute longitudinal, transverse, and unsigned flux density of large granules are smaller than those of small granules; (3) for small granules, the average of continuum intensity increases with their diameters, while the averages of Doppler velocity, transverse, absolute longitudinal, and unsigned magnetic flux density decrease with their diameters. However, the mean properties of large granules are stable; (4) the intensity distributions of all granules and small granules do not satisfy Gaussian distribution, while that of large granules almost agrees with normal distribution with a peak at 1.04 I

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

    Science.gov (United States)

    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

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

    Science.gov (United States)

    Schmitner, Nicole; Kohno, Kenji; Meyer, Dirk

    2017-03-01

    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 conclusion, we

  18. Regulation

    International Nuclear Information System (INIS)

    Ballereau, P.

    1999-01-01

    The different regulations relative to nuclear energy since the first of January 1999 are given here. Two points deserve to be noticed: the decree of the third august 1999 authorizing the national Agency for the radioactive waste management to install and exploit on the commune of Bures (Meuse) an underground laboratory destined to study the deep geological formations where could be stored the radioactive waste. The second point is about the uranium residues and the waste notion. The judgment of the administrative tribunal of Limoges ( 9. july 1998) forbidding the exploitation of a storage installation of depleted uranium considered as final waste and qualifying it as an industrial waste storage facility has been annulled bu the Court of Appeal. It stipulated that, according to the law number 75663 of the 15. july 1965, no criteria below can be applied to depleted uranium: production residue (possibility of an ulterior enrichment), abandonment of a personal property or simple intention to do it ( future use aimed in the authorization request made in the Prefecture). This judgment has devoted the primacy of the waste notion on this one of final waste. (N.C.)

  19. Balloon cells associated with granule cell dispersion in the dentate gyrus in hippocampal sclerosis.

    Science.gov (United States)

    Thom, M; Martinian, L; Caboclo, L O; McEvoy, A W; Sisodiya, S M

    2008-06-01

    Granule cell dispersion (GCD) is a common finding in hippocampal sclerosis in patients with intractable focal epilepsy. It is considered to be an acquired, post-developmental rather than a pre-existing abnormality, involving dispersion of either mature or newborn neurones, but the precise factors regulating it and its relationship to seizures are unknown. We present two cases of GCD with associated CD34-immunopositive balloon cells, a cell phenotype associated with focal cortical dysplasia type IIB, considered to be a developmental cortical lesion promoting epilepsy. This observation opens up the debate regarding the origin of balloon cells and CD34 expression and their temporal relationship to seizures.

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

    International Nuclear Information System (INIS)

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

    2003-01-01

    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 β-emitting radionuclides, such as lutetium-177 and yttrium-90. Based on serum stability (4 h incubation at 37 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 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- and DOTA-conjugated NT

  1. The impact of pancreaticoduodenectomy on endocrine and exocrine pancreatic function: A prospective cohort study based on pre- and postoperative function tests.

    Science.gov (United States)

    Roeyen, Geert; Jansen, Miet; Hartman, Vera; Chapelle, Thiery; Bracke, Bart; Ysebaert, Dirk; De Block, Christophe

    Studies reporting on function after pancreatic surgery are frequently based on diabetes history, fasting glycemia or random glycemia. The aim of this study was to investigate prospectively the evolution of pancreatic function in patients undergoing pancreaticoduodenectomy based on proper pre- and postoperative function tests. It was hypothesised that pancreatic function deteriorates after pancreaticoduodenectomy. Between 2013 and 2016, 78 patients undergoing pancreaticoduodenectomy for oncologic indications had a prospective evaluation of their endocrine and exocrine pancreatic function. Endocrine function was evaluated with the 75 g oral glucose tolerance test (OGTT) and the 1 mg intravenous glucagon test. Exocrine function was evaluated with a 13C-labelled mixed-triglyceride breath test. Tests were performed pre- and postoperatively. In 90.5% (19/21) of patients with preoperatively known diabetes, no change in endocrine function was observed. In contrast, endocrine function improved in 68.1% (15/22) of patients with newly diagnosed diabetes. 40% (14/35) of patients with a preoperative normal OGTT or prediabetes experienced deterioration in function. In multivariate analysis, improvement of newly diagnosed diabetes was correlated with preoperative bilirubin levels (p = 0.045), while progression towards diabetes was correlated with preoperative C-peptidogenic index T 30 (p = 0.037). A total of 20.5% (16/78) of patients had pancreatic exocrine insufficiency preoperatively. Another 51.3% (40/78) of patients deteriorated on exocrine level. In total, 64.1% (50/78) of patients required pancreatic enzyme-replacement therapy postoperatively. Although deterioration of endocrine function was expected after pancreatic resection, improvement is frequently observed in patients with newly diagnosed diabetes. Exocrine function deteriorates after pancreaticoduodenectomy. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  2. Effects of Bufei Yishen Granules Combined with Acupoint Sticking Therapy on Pulmonary Surfactant Proteins in Chronic Obstructive Pulmonary Disease Rats

    Directory of Open Access Journals (Sweden)

    Yange Tian

    2016-01-01

    Full Text Available Our previous studies have demonstrated the beneficial effects of Bufei Yishen granules combined with acupoint sticking therapy (the integrated therapy in chronic obstructive pulmonary disease (COPD, but the underlying mechanism remains unclear. Dysfunction of pulmonary surfactant proteins (SPs, including SP-A, SP-B, SP-C, and SP-D may be included in pathophysiology of COPD. This study aimed to explore the mechanism of the integrated therapy on SPs. COPD rat models were established. The treatment groups received Bufei Yishen granules or acupoint sticking or their combination. Using aminophylline as a positive control drug. The levels of SPs in serum, BALF, and lung were measured. The results showed that the integrated therapy markedly reduced the levels of SPs in serum and increased these indicators in the lung. The integrated therapy was better than aminophylline in reducing the levels of SPs and was better than Bufei Yishen granules in reducing SP-A, SP-C, and SP-D in serum. The integrated therapy was better than aminophylline and Bufei Yishen granules in increasing SP-A, SP-B, and SP-D mRNA in the lung. SP-A and SP-D in BALF were positively correlated with PEF and EF50. The levels of SPs are associated with airway limitation. The beneficial effects of the integrated therapy may be involved in regulating pulmonary surfactant proteins.

  3. Proneurotrophin-3 promotes cell cycle withdrawal of developing cerebellar granule cell progenitors via the p75 neurotrophin receptor.

    Science.gov (United States)

    Zanin, Juan Pablo; Abercrombie, Elizabeth; Friedman, Wilma J

    2016-07-19

    Cerebellar granule cell progenitors (GCP) proliferate extensively in the external granule layer (EGL) of the developing cerebellum prior to differentiating and migrating. Mechanisms that regulate the appropriate timing of cell cycle withdrawal of these neuronal progenitors during brain development are not well defined. The p75 neurotrophin receptor (p75(NTR)) is highly expressed in the proliferating GCPs, but is downregulated once the cells leave the cell cycle. This receptor has primarily been characterized as a death receptor for its ability to induce neuronal apoptosis following injury. Here we demonstrate a novel function for p75(NTR) in regulating proper cell cycle exit of neuronal progenitors in the developing rat and mouse EGL, which is stimulated by proNT3. In the absence of p75(NTR), GCPs continue to proliferate beyond their normal period, resulting in a larger cerebellum that persists into adulthood, with consequent motor deficits.

  4. Localization of SERBP1 in stress granules and nucleoli.

    Science.gov (United States)

    Lee, Yu-Jen; Wei, Hung-Ming; Chen, Ling-Yun; Li, Chuan

    2014-01-01

    SERPINE1 mRNA-binding protein 1 (SERBP1) is an arginine-methylated RNA-binding protein whose modification affects protein interaction and intracellular localization. In the present study, we show that, under normal growth conditions without stress, SERBP1 interacts with arginine-methylated and stress granule-associated proteins such as heterogeneous nuclear ribonucleoprotein A1, fragile X mental retardation protein and fragile X mental retardation syndrome-related protein 1 in an RNA-dependent manner. We also show that, after arsenite treatment, a proportion of full-length SERBP1 protein co-localizes with the typical stress granule marker T-cell intracellular antigen-1 in the cytoplasmic stress granules. Truncated SERBP1 with an N-terminal, central RG or C-terminal deletion, or single-domain segments comprising the N-terminal, central or C-terminal region, were recruited to stress granules upon arsenite treatment but with reduced efficiency. In addition, upon arsenite treatment, the localization of SERBP1 changed from a diffuse cytoplasmic localization to nuclear-dominant (concentrated in the nucleolus) A similar distribution was observed when cells were treated with the methylation inhibitor adenosine periodate, and was also detected for N- or C-terminal domain deletions and all three single-domain fragments even without stress induction. We further demonstrate that adenosine periodate treatment delays the association/dissociation of SERBP1 with stress granules. Hypomethylation retains SERBP1 in the nucleus/nucleolus regardless of arsenite treatment. Our study indicates that arginine methylation is correlated with recruitment of SERBP to stress granules and nucleoli and its retention therein. To our knowledge, this is the first report of an RNA-binding protein that is shifted simultaneously to cytoplasmic stress granules and nucleoli, two ribonucleoprotein-enriched subcellular compartments, upon stress. © 2013 FEBS.

  5. Recent results and prospects on superheated superconducting granules detectors

    International Nuclear Information System (INIS)

    Gonzalez-Mestres, L.; Perret-Gallix, D.

    1987-11-01

    The basic properties of superheated superconducting granules (SSG) detectors are reviewed. Recent results are presented and discussed. Granule samples of different sizes (10 μm -8 Ω.cm -6 Ω.cm) exhibit encouraging sensitivity to low energy β and γ sources (down to 55 Fe 6 KeV γ'S). All tests were performed with real-time read-out electronics, detecting single granule flips under the action of individual particles. Sensitivity is shown to depend on normal state resistivity. Irradiation of very large tin granules (45 μm ≤ Φ ≤ 400 μm) with α particles ( 241 Am, E ≅ 5.5 MeV) shows evidence for local heating, where the observed energy threshold is far below the one predicted by equilibrium thermodynamical calculations. Tests made at lower temperatures (T ≥ 450 mK) show the absence of avalanche effect (seen by other authors in different conditions) for several samples of tin granules. A theoretical discussion of the avalanche effect is presented. The understanding of the role of heat exchanges in the composite medium leads to the concept of 'localized micro-avalanche' and opens the way to drastic improvements of SSG performance for particle detection. Such a phenomenon should be obtained by a better thermal matching between dielectric and granules, working at temperatures where the released latent heat is slightly positive. Estimates of the behavior of the detector at very low T are also given, where a thin layer of normal electrons near the surface is shown to contribute to the heat capacity of a superheated granule. We discuss the main points to be studied in the near future, and give a brief evaluation of the present status of feasibility investigation for several proposed experiments (solar neutrinos, monopoles, dark matter, double β,...). An updated working program for SSG development is proposed

  6. Exocrine pancreatic secretion is stimulated in piglets fed Fish oil compared with those fed Coconut Oil or Lard

    DEFF Research Database (Denmark)

    Hedemann, Mette Skou; Pedersen, Asger Roer; Engberg, Ricarda M.

    2001-01-01

    An experiment was conducted to study the effect of feeding diets containing fat sources with different fatty acid composition (fish oil, coconut oil or lard, 10 g/100 g diet) on exocrine pancreatic secretion in piglets after weaning. A total of 16 barrows were weaned at 4 wk of age; 3 d later...... the coconut oil or lard diets. The output [U/(h. kg(0.75))] of lipase was higher in piglets fed fish oil than in piglets fed lard or coconut oil. The output of colipase was greater in piglets fed fish oil and coconut oil than in those fed lard. The dietary treatments did not affect the output of carboxylester...... hydrolase. The output of trypsin was significantly lower in piglets fed lard than in piglets fed fish oil or coconut oil diets and the output of carboxypeptidase B was greater in those fed the fish oil diet. Protein, chymotrypsin, carboxypeptidase A, elastase and amylase outputs did not differ among...

  7. Exocrine and endocrine pancreatic function in 21 patients suffering from autoimmune pancreatitis before and after steroid treatment.

    Science.gov (United States)

    Frulloni, Luca; Scattolini, Chiara; Katsotourchi, Anna Maria; Amodio, Antonio; Gabbrielli, Armando; Zamboni, Giuseppe; Benini, Luigi; Vantini, Italo

    2010-01-01

    Autoimmune pancreatitis (AIP) responds rapidly and dramatically to steroid therapy. The aim of this study was to evaluate pancreatic exocrine and endocrine function in patients suffering from AIP both before and after steroid therapy. Fecal elastase 1 and diabetes were evaluated before steroid therapy and within 1 month of its suspension in 21 patients (13 males and 8 females, mean age 43 +/- 16.5 years) diagnosed as having AIP between 2006 and 2008. At clinical onset, fecal elastase 1 was 107 +/- 126 microg/g stool. Thirteen patients (62%) showed severe pancreatic insufficiency (insufficiency (100-200 microg/g stool), while 4 (19%) had normal pancreatic function (>200 microg/g stool). Before steroids, diabetes was diagnosed in 5 patients (24%), all of whom had very low levels of fecal elastase 1 (endocrine pancreatic insufficiency at clinical onset. These insufficiencies improve after steroid therapy. Copyright 2010 S. Karger AG, Basel.

  8. Exocrine and endocrine testicular function during the treatment of experimental orchitis and nonspecific orchoepididymitis by low-energy laser radiation

    Science.gov (United States)

    Reznikov, Leonid L.; Pupkova, Ludmila S.; Bell, H.; Murzin, Alexander G.

    1995-05-01

    Investigations into the biological effects of low-energy laser radiation (LLR) are characterized by a score of challenges, which are due primarily to a cascade of laser-induced and sometimes antagonistic processes. To investigate these processes on various biologic levels, we analyzed local and general effects of LLR on the exocrine and endocrine functions of the accessory sex glands in experimentally induced orchitis and orchoepididymitis in rabbits, and in clinical studies on male patients. The results indicate that LLR may alter the inflammatory response, including the exudative reaction, macrophage migration, and fibroblast activity. Furthermore, LLR may result in changes in serum concentrations of LH, FSH, and ACTH, prolactin, testosterone, cortisol and aldosterone. Some of these changes may be at least partially responsible for the well-known anti-inflammatory effects of LLR.

  9. [Protective effect and mechanism of compound Ginkgo biloba granules on oxidative stress injury of HUVEC].

    Science.gov (United States)

    Li, Qi; Chen, Xi; Kan, Xiao-Xi; Li, Yu-Jie; Yang, Qing; Wang, Ya-Jie; Chen, Ying; Weng, Xiao-Gang; Cai, Wei-Yan; Huang, He-Fei; Zhu, Xiao-Xin

    2016-02-01

    To reveal the protective and anti-apoptosis effect of compound Ginkgo biloba granules on oxidative stress injury of human umbilical vein endothelial cells (HUVEC). Negative control group, H2O2 model group and 4 drug pretreatment groups (80, 160, 320, 640 mg• L⁻¹) were established. The cell proliferation, morphological changes in each group after oxidative stress injury was detected by MTT assay and through microscope observation respectively. The content of LDH, MDA, SOD and NO and SOD activity in supernatant were detected to judge the protection effect of the drugs on endothelial cells. The protective effect on HUVEC apoptosis was analyzed by Caspase-3 activity test and Annexin V-FITC/PI staining. Western blot was used to observe the expression of apoptosis-related proteins Bcl-2 and Bax. Results showed that 1 200 μmol• L⁻¹ H2O2 can induce oxidative stress injury in endothelial cells and reduce the cell survival rate; cell proliferation inhibition degree is positively correlated with the effect time of H2O2. Besides, 80, 160, 320 640 mg•L⁻¹ compound Ginkgo biloba granules can protect HUVEC from oxidative stress injury, recover the normal proliferation level of cells, improve their state, prohibit cell apoptosis, and can up-regulate and down-regulate the expression level of Bcl-2 and Bax respectively. In conclusion, compound G. biloba granules can protect HUVEC from the oxidative stress injury induced by H2O2, its mechanism may be correlated with inhibition of the mitochondrial apoptotic pathway in HUVEC. Copyright© by the Chinese Pharmaceutical Association.

  10. Spatio-temporal Dynamics and Mechanisms of Stress Granule Assembly.

    Directory of Open Access Journals (Sweden)

    Daisuke Ohshima

    2015-06-01

    Full Text Available Stress granules (SGs are non-membranous cytoplasmic aggregates of mRNAs and related proteins, assembled in response to environmental stresses such as heat shock, hypoxia, endoplasmic reticulum (ER stress, chemicals (e.g. arsenite, and viral infections. SGs are hypothesized as a loci of mRNA triage and/or maintenance of proper translation capacity ratio to the pool of mRNAs. In brain ischemia, hippocampal CA3 neurons, which are resilient to ischemia, assemble SGs. In contrast, CA1 neurons, which are vulnerable to ischemia, do not assemble SGs. These results suggest a critical role SG plays in regards to cell fate decisions. Thus SG assembly along with its dynamics should determine the cell fate. However, the process that exactly determines the SG assembly dynamics is largely unknown. In this paper, analyses of experimental data and computer simulations were used to approach this problem. SGs were assembled as a result of applying arsenite to HeLa cells. The number of SGs increased after a short latent period, reached a maximum, then decreased during the application of arsenite. At the same time, the size of SGs grew larger and became localized at the perinuclear region. A minimal mathematical model was constructed, and stochastic simulations were run to test the modeling. Since SGs are discrete entities as there are only several tens of them in a cell, commonly used deterministic simulations could not be employed. The stochastic simulations replicated observed dynamics of SG assembly. In addition, these stochastic simulations predicted a gamma distribution relative to the size of SGs. This same distribution was also found in our experimental data suggesting the existence of multiple fusion steps in the SG assembly. Furthermore, we found that the initial steps in the SG assembly process and microtubules were critical to the dynamics. Thus our experiments and stochastic simulations presented a possible mechanism regulating SG assembly.

  11. The influence of substrate transport limitation on porosity and methanogenic activity of anaerobic sludge granules

    Energy Technology Data Exchange (ETDEWEB)

    Alphenaar, P.A. (Agricultural Univ., Wageningen (Netherlands). Dept. of Environmental Technology); Perez, M.C. (Agricultural Univ., Wageningen (Netherlands). Dept. of Environmental Technology); Lettinga, G. (Agricultural Univ., Wageningen (Netherlands). Dept. of Environmental Technology)

    1993-05-01

    The relationship between porosity, diameter and methanogenic activity of anaerobic granules has been investigated. Experiments with different granular sludges revealed that substrate transport limitations increase with the diameter of the granules. As a consequence, autolysis can occur in the core of the granule, producing hollow granules. The porosity measurements revealed that the hollow centre is not available for substrate transport. Possibly as an effect of bacterial lysis, the porosity decreases in the more interior layers of the granules. This results in a inactive inner part of the large granules, which is not involved in the treatment process; the specific methanogenic activity decreases with granule size. No marked difference in substrate affinity is observed between granules of different sizes, which probably indicates that for large granules only the exterior is biological active. (orig.)

  12. Correlation between microbial community and granule conductivity in anaerobic bioreactors for brewery wastewater treatment

    DEFF Research Database (Denmark)

    Shrestha, Pravin; Malvankar, Nikhil S.; Werner, Jeffrey

    2014-01-01

    Prior investigation of an upflow anaerobic sludge blanket (UASB) reactor treating brewery wastes suggested that direct interspecies electron transfer (DIET) significantly contributed to interspecies electron transfer to methanogens. To investigate DIET in granules further, the electrical conducti......Prior investigation of an upflow anaerobic sludge blanket (UASB) reactor treating brewery wastes suggested that direct interspecies electron transfer (DIET) significantly contributed to interspecies electron transfer to methanogens. To investigate DIET in granules further, the electrical...... conductivity and bacterial community composition of granules in fourteen samples from four different UASB reactors treating brewery wastes were investigated. All of the UASB granules were electrically conductive whereas control granules from ANAMMOX (ANaerobic AMMonium OXidation) reactors and microbial...... granules from an aerobic bioreactor designed for phosphate removal were not. There was a moderate correlation (r = 0.67) between the abundance of Geobacter species in the UASB granules and granule conductivity, suggesting that Geobacter contributed to granule conductivity. These results, coupled...

  13. Granulation of Cu-Al-Fe-Ni Bronze

    Directory of Open Access Journals (Sweden)

    Pisarek B.P.

    2014-08-01

    Full Text Available With the increase in wall thickness of the casting of iron-nickel-aluminium-bronze, by the reduction of the cooling rate the size of κII phase precipitates increases. This process, in the case of complex aluminium bronzes with additions of Cr, Mo and W is increased. Crystallization of big κII phase, during slow cooling of the casting, reduces the concentration of additives introduced to the bronze matrix and hardness. Undertaken research to develop technology of thick-walled products (g> 6 mm of complex aluminium bronzes. Particular attention was paid to the metallurgy of granules. As a result, a large cooling speed of the alloy, and also high-speed solidification casting a light weight of the granules allows: to avoid micro-and macrosegregation, decreasing the particle size, increase the dispersion of phases in multiphase alloys. Depending on the size granules as possible is to provide finished products with a wall thickness greater than 6 mm by infiltration of liquid alloy of granules (composites. Preliminary studies was conducted using drip method granulate of CuAl10Fe5Ni5 bronze melted in a INDUTHERM-VC 500 D Vacuum Pressure Casting Machine. This bronze is a starting alloy for the preparation of the complex aluminium bronzes with additions of Cr, Mo, W and C or Si. Optimizations of granulation process was carried out. As the process control parameters taken a casting temperature t (°C and the path h (mm of free-fall of the metal droplets in the surrounding atmosphere before it is intensively cooled in a container of water. The granulate was subjected to a sieve analysis. For the objective function was assume maximize of the product of Um*n, the percentage weight “Um” and the quantity of granules ‘n’ in the mesh fraction. The maximum value of the ratio obtained for mesh fraction a sieve with a mesh aperture of 6.3 mm. In the intensively cooled granule of bronze was identified microstructure composed of phases: β and fine bainite

  14. Pelletizing of NaF granules as adsorbent for fluorides of nuclear fuel materials, (1)

    International Nuclear Information System (INIS)

    Kimura, Syojiro; Tsutsui, Tenson; Kanagawa, Akira.

    1976-01-01

    The pelletizing of NaF granules on laboratory scale used for recovery and purification of fluorides of nuclear fuel materials are investigated, particularity experimental studies on how to pelletize, fluidity of granules and flow rate of the granules in mortar of tablet machine are carried out. As result, added quantity of H 2 O as binder at granulation process of spherical NaF granule influence to yield of NaF granules. The proper quantity of H 2 O to NaF powder is about 18--19%. Friction coefficient of unfixed shape NaF granule is higher than that of spherical granule, in opposition, density of the former granule is lower. So fluidity of unfixed shape NaF granule is low, flow rate of the granules through feeder of tablet machine is slow, and arching on mortar of the tablet machine occurs. Then, some further operation for getting better fluidity needs for pelletizing of NaF granules using unfixed shape granule. The other hand, using spherical NaF granule, continuous pelletizing by commercial tablet machine can be carried out. (auth.)

  15. Studi Awal Desain Pabrik Pupuk Organik Granul Dari Organic Waste

    Directory of Open Access Journals (Sweden)

    Zulfatul Hanna

    2015-12-01

    Full Text Available 800x600 Banyak pertanian di Indonesia yang masih bergantung pada penggunaan pupuk kimia. Padahal penggunaan pupuk kimia yang berlebihan dapat menyebabkan penurunan bahan organik tanah. Untuk menyeimbangkannnya saat ini petani juga sedang menggalakkan penggunaan pupuk organik. Sehingga membuat kebutuhan pupuk organik meningkat setiap tahunnya. Pendirian pabrik pupuk organik granul ini dapat memenuhi kebutuhan pupuk organik untuk petani. Prosess pembuatan pupuk organik granul terdiri dari pencampuran bahan baku, yakni sampah organik, kotoran sapi, kotoran domba, dan dipotong dengan rotary knife cutter. Tahap berikutnya adalah proses fermentasi, dengan penambahan bioactivator agar meningkatkan kandungan C-organik, phosphor, dan kalium. Selanjutnya adalah proses granulasi, pembesaran dari partikel dengan proses aglomerasi. Ukuran yang diharapkan pada proses granulasi ini adalah 2-4 mm sehingga produk undersize maupun oversize akan dikembalikan ke dalam granulator setelah melewati screener. Selanjutnya pupuk organik granul dikeringkan. Selanjutnya produk dipisahkan berdasarkan ukurannya lalu didinginkan di Rotary cooler. Setelah keluar dari Rotary Cooler suhu keluaran sekitar 40 oC dan masih mengandung kadar air sebesar 13,7%. Produk dari rotary cooler siap untuk di packaging dan masuk ke dalam pupuk organik granul storage. Dari analisa ekonomi didapatkan BEP sebesar 45% dengan POT sesudah pajak sebesar 4,8 tahun. Normal 0 false false false IN X-NONE X-NONE MicrosoftInternetExplorer4

  16. Preparation of porcelain tile granulates by more environmentally sustainable processes

    Energy Technology Data Exchange (ETDEWEB)

    Gil, C.; Silvestre, D.; Piquer, J.; Garcia-Ten, J.; Quereda, E.; Vicente, M. J.

    2012-07-01

    This study examines the feasibility of manufacturing glazed porcelain tiles with a more environmentally friendly manufacturing process, by reducing water and thermal energy consumption. The process studied in this paper is dry milling in a pendulum mill, with subsequent granulation (in order to obtain a press powder with similar flow ability to that of spray dried powders). The different morphology of the new granulate with respect to the standard spray-dried granulate modifies the microstructure of the green compacts and thus, their behaviour and fired tile properties. In order to obtain porcelain tiles with the required properties (water absorption, mechanical strength,) changes have been made in the raw materials mixture and in the processing variables. Finally, porcelain tiles measuring 50x50 cm have been manufactured at industrial scale with the new granulate using a conventional firing cycle, obtaining quality levels identical to those provided by the spray-dried granulate. These results open the possibility of preparing porcelain tile body compositions through a manufacturing process alternative to the standard one, more environmentally friendly and with lower costs. (Author)

  17. Physicochemical and tablet properties of Cyperus alulatus rhizomes starch granules.

    Science.gov (United States)

    Paramakrishnan, N; Jha, S; Kumar, K Jayaram

    2015-05-01

    The starch extracted from rhizomes of Cyperus alulatus (CA) was characterized for its physicochemical, morphological and tableting properties. Rhizomes of CA yield a significant quantity of starch granules (CASG) i.e., 11.93%. CASG was characterized in terms of moisture, ash and amylose contents, solubility and swelling power, paste clarity and water retention capacity. The swelling power was found to be significantly improved with the increase in temperature. Scanning electron micrographs revealed that the granule's surface was smooth, the granules were spherical, mostly round, disc like, and the size range was 6.65-12.13 μm. Finger print region in FTIR spectra confirmed its carbohydrate nature. The evaluated micromeritic properties of extracted granule's bulk density, tapped density, Carr's index, Hausner ratio, true density and porosity render unique practicability of CASG being used as an adjuvant in pharmaceutical solid dosage forms. Tablets prepared by using CASG showed higher mechanical strength and more disintegration time, which depicted the characteristic binding nature of the starch granules. As CASG is imparting better binding properties in less concentration and also it can be used in combination with the established starches to get the synergistic effect; this starch can be used commercially in the tablet preparation. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Competition from newborn granule cells does not drive axonal retraction of silenced old granule cells in the adult hippocampus

    Directory of Open Access Journals (Sweden)

    Carla M Lopez

    2012-11-01

    Full Text Available In the developing nervous system synaptic refinement, typified by the neuromuscular junction where supernumerary connections are eliminated by axon retraction leaving the postsynaptic target innervated by a single dominant input, critically regulates neuronal circuit formation. Whether such competition based pruning continues in established circuits of mature animals remains unknown. This question is particularly relevant in the context of adult neurogenesis where newborn cells must integrate into preexisting circuits, and thus, potentially compete with functionally mature synapses to gain access to their postsynaptic targets. The hippocampus plays an important role in memory formation/retrieval and the dentate gyrus subfield (DG exhibits continued neurogenesis into adulthood. Therefore, this region contains both mature granule cells (old GCs and immature recently born GCs that are generated throughout adult life (young GCs, providing a neurogenic niche model to examine the role of competition in synaptic refinement. Recent work from an independent group in developing animals indicated that embryonically/early postnatal generated GCs placed at a competitive disadvantage by selective expression of tetanus toxin (TeTX to prevent synaptic release rapidly retracted their axons, and that this retraction was driven by competition from newborn GCs lacking TeTX. In contrast, following 3-6 months of selective TeTX expression in old GCs of adult mice we did not observe any evidence of axon retraction. Indeed ultrastructural analyses indicated that the terminals of silenced GCs even maintained synaptic contact with their postsynaptic targets. Furthermore, we did not detect any significant differences in the electrophysiological properties between old GCs in control and TeTX conditions. Thus, our data demonstrate a remarkable stability in the face of a relatively prolonged period of altered synaptic competition between two populations of neurons within the

  19. Removal of strontium ions from solutions using granulated zeolites

    International Nuclear Information System (INIS)

    Bronic, J.; Subotic, B.

    1992-01-01

    The ion-exchange process on columns filled with granulated zeolites is determined by several physico-chemical parameters. The influence of these parameters (zeolite type, concentration of exchangeable ions in solution, temperature, flow rate, etc.) on the kinetics of ion-exchange process was studied by measuring the Sr 2+ ion concentration in solution before and after passing through a column filled with various granulated zeolites (zeolite 13X, zeolite A and synthetic mordenite). Using the experimental technique of radioactive labeling by 89 Sr, the distribution of Sr 2+ ions in column fillings were also determined. From the results obtained, the optimal conditions for the most efficient removal of strontium ions from solutions using granulated zeolites can be defined. (author) 24 refs.; 9 figs

  20. Superheated superconducting granule detector tested with nuclear recoil measurements

    International Nuclear Information System (INIS)

    Berger, C.; Czapek, G.; Diggelmann, U.; Flammer, I.; Frei, D.; Furlan, M.; Gabutti, A.; Janos, S.; Moser, U.; Pretzl, K.; Schmiemann, K.; Perret-Gallix, D.; Brandt, B. van den; Konter, J.A.; Mango, S.

    1993-01-01

    The presented results are part of a superheated superconducting granule (SSG) detector development for neutrino and dark matter. The aim of the experiment was to measure the sensitivity of the detector to nuclear recoil energies when exposed to a 70 MeV neutron beam. The detector consists of a small readout coil (diameter 5 mm, length 10 mm) filled with aluminum granules of average diameter 23 μm embedded in an Al 2 O 3 granulate with a 6% volume filling factor. The neutron scattering angles were determined using a scintillator hodoscope. Coincidences between the SSG and the hodoscope signals have been clearly established. Data were taken at an operating temperature of 120 mK for different SSG intrinsic thresholds. The results prove the sensitivity of the detector to nuclear recoils around 10 keV. (orig.)

  1. [Pharmacological availability of erythromycin granules for children's use].

    Science.gov (United States)

    Korenev, S V; Garsheva, G B; Nesterova, L Ia; Grakovskaia, L K; Tentsova, A I

    1990-08-01

    Pharmaceutical availability of erythromycin granules with polymeric coating of different composition+ was studied. With an account of the ++anatomo-physiological features of a child organism and the properties of the antibiotic, acetylphthalyl cellulose in combination with hydroxypropyl methylcellulose or methyl cellulose was used as a film forming agent. The coated granules were estimated by such parameters as the time of disintegration and the rate of dissolution in various media. The results of the study showed that coating of the erythromycin granules with the film composed of acetylphthalyl cellulose and hydroxypropyl methylcellulose in the ratio of 8 to 2 provided the required protection of the antibiotic in acid media and high pharmaceutical availability of the drug.

  2. Olfactory granule cell development in normal and hyperthyroid rats.

    Science.gov (United States)

    Brunjes, P C; Schwark, H D; Greenough, W T

    1982-10-01

    Dendritic development was examined in olfactory bulbs of both normal 7-, 14-, 21- and 60-day-old rats and littermates treated on postnatal days 1-4 with 1 microgram/g body weight of L-thyroxine sodium. Tissue was processed via the Golgi-Cox technique and subjected to quantitative analyses of mitral and internal layer granule cell development. These populations of granule cells were selected because their pattern of late proliferation suggested potentially greater susceptibility to postnatal hormonal alterations. Although neonatal hyperthyroidism induces widespread acceleration of maturation, including precocious chemosensitivity, granule cell development was unaffected relative to littermate controls. Both normal and hyperthyroid groups exhibited an inverted U-shaped pattern of cellular development, with rapid dendritic dendritic growth and expansion occurring during the earliest ages tested, but with loss of processes and dendritic field size occurring after day 21.

  3. UVC-induced stress granules in mammalian cells.

    Directory of Open Access Journals (Sweden)

    Mohamed Taha Moutaoufik

    Full Text Available Stress granules (SGs are well characterized cytoplasmic RNA bodies that form under various stress conditions. We have observed that exposure of mammalian cells in culture to low doses of UVC induces the formation of discrete cytoplasmic RNA granules that were detected by immunofluorescence staining using antibodies to RNA-binding proteins. UVC-induced cytoplasmic granules are not Processing Bodies (P-bodies and are bone fide SGs as they contain TIA-1, TIA-1/R, Caprin1, FMRP, G3BP1, PABP1, well known markers, and mRNA. Concomitant with the accumulation of the granules in the cytoplasm, cells enter a quiescent state, as they are arrested in G1 phase of the cell cycle in order to repair DNA damages induced by UVC irradiation. This blockage persists as long as the granules are present. A tight correlation between their decay and re-entry into S-phase was observed. However the kinetics of their formation, their low number per cell, their absence of fusion into larger granules, their persistence over 48 hours and their slow decay, all differ from classical SGs induced by arsenite or heat treatment. The induction of these SGs does not correlate with major translation inhibition nor with phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α. We propose that a restricted subset of mRNAs coding for proteins implicated in cell cycling are removed from the translational apparatus and are sequestered in a repressed form in SGs.

  4. Giant arachnoid granulation: differential diagnosis of acute headache

    International Nuclear Information System (INIS)

    Peters, S.A.; Heyer, C.M.; Frombach, E.

    2007-01-01

    Full text: We present a case of intense, rapidly evolving headache clinically mimicking meningitis, subarachnoid haemorrhage or venous sinus thrombosis. Clinical examination, standard blood work and central nervous system studies were non-contributory and effectively ruled out these diagnoses. Cranial multidetector CT studies before and after application of intravenous contrast medium performed prior to lumbar tap disclosed a non-enhancing ovoid mass filling the superior sagittal sinus. This lesion posed a differential to venous sinus thrombosis, but ultimately fulfilled the criteria of a giant arachnoid granulation. The imaging characteristics and differential diagnosis of giant arachnoid granulations are discussed

  5. Morphological Constraints on Cerebellar Granule Cell Combinatorial Diversity.

    Science.gov (United States)

    Gilmer, Jesse I; Person, Abigail L

    2017-12-13

    Combinatorial expansion by the cerebellar granule cell layer (GCL) is fundamental to theories of cerebellar contributions to motor control and learning. Granule cells (GrCs) sample approximately four mossy fiber inputs and are thought to form a combinatorial code useful for pattern separation and learning. We constructed a spatially realistic model of the cerebellar GCL and examined how GCL architecture contributes to GrC combinatorial diversity. We found that GrC combinatorial diversity saturates quickly as mossy fiber input diversity increases, and that this saturation is in part a consequence of short dendrites, which limit access to diverse inputs and favor dense sampling of local inputs. This local sampling also produced GrCs that were combinatorially redundant, even when input diversity was extremely high. In addition, we found that mossy fiber clustering, which is a common anatomical pattern, also led to increased redundancy of GrC input combinations. We related this redundancy to hypothesized roles of temporal expansion of GrC information encoding in service of learned timing, and we show that GCL architecture produces GrC populations that support both temporal and combinatorial expansion. Finally, we used novel anatomical measurements from mice of either sex to inform modeling of sparse and filopodia-bearing mossy fibers, finding that these circuit features uniquely contribute to enhancing GrC diversification and redundancy. Our results complement information theoretic studies of granule layer structure and provide insight into the contributions of granule layer anatomical features to afferent mixing. SIGNIFICANCE STATEMENT Cerebellar granule cells are among the simplest neurons, with tiny somata and, on average, just four dendrites. These characteristics, along with their dense organization, inspired influential theoretical work on the granule cell layer as a combinatorial expander, where each granule cell represents a unique combination of inputs

  6. Method of production of granulates of ceramic nuclear fuels

    International Nuclear Information System (INIS)

    Wilkinson, W.L.

    1975-01-01

    To obtain a classified granulate of ceramic nuclear fuels with narrow grain size spectrum, the nuclear fuel powder is made into a slurry in a non-aqueous solvent with a water content as low as possible (e.g. chlorated hydrocarbon), a binder added to it, and spray-dried. The dry granulate desired is already obtained by this working stage. Polybutyl methacrylate in dibutylphthalate is proposed as binder. An example in which uranium dioxide powder is slurried in trichloro-ethylene is described in detail. (UWI/LH) [de

  7. Removal of cesium radioisotopes from solutions using granulated zeolites

    International Nuclear Information System (INIS)

    Bronic, J.; Subotic, B.

    1991-01-01

    The influence of type of zeolite and the flow rate of solution through the column on the removal efficiency of radioactive cesium ions from solution has been investigated. The analysis of the change in the concentration of cesium ions in the solutions and distribution of cesium ions in the column fillings (granulated zeolites), after passing the solutions through the columns filled with various granulated zeolites (zeolite 4A, zeolite 13X, synthetic mordenite) was performed. On the basis of the results of this study, the conditions for the most efficient removal of cesium ions from solutions have been discussed. (author) 35 refs.; 9 figs.; 1 tab

  8. PHB granules are attached to the nucleoid via PhaM in Ralstonia eutropha.

    Science.gov (United States)

    Wahl, Andreas; Schuth, Nora; Pfeiffer, Daniel; Nussberger, Stephan; Jendrossek, Dieter

    2012-11-16

    Poly(3-hydroxybutyrate) (PHB) granules are important storage compounds of carbon and energy in many prokaryotes which allow survival of the cells in the absence of suitable carbon sources. Formation and subcellular localization of PHB granules was previously assumed to occur randomly in the cytoplasm of PHB accumulating bacteria. However, contradictionary results on subcellular localization of PHB granules in Ralstonia eutropha were published, recently. Here, we provide evidence by transmission electron microscopy that PHB granules are localized in close contact to the nucleoid region in R. eutropha during growth on nutrient broth. Binding of PHB granules to the nucleoid is mediated by PhaM, a PHB granule associated protein with phasin-like properties that is also able to bind to DNA and to phasin PhaP5. Over-expression of PhaM resulted in formation of many small PHB granules that were always attached to the nucleoid region. In contrast, PHB granules of ∆phaM strains became very large and distribution of granules to daughter cells was impaired. Association of PHB granules to the nucleoid region was prevented by over-expression of PhaP5 and clusters of several PHB granules were mainly localized near the cell poles. Subcellular localization of PHB granules is controlled in R. eutropha and depends on the presence and concentrations of at least two PHB granule associated proteins, PhaM and PhaP5.

  9. Phenotypic properties and microbial diversity of methanogenic granules from a full-scale UASB reactor treating brewery wastewater

    NARCIS (Netherlands)

    Diaz, E.E.; Stams, A.J.M.; Amils, R.; Sanz, J.L.

    2006-01-01

    Methanogenic granules from an anaerobic bioreactor that treated wastewater of a beer brewery consisted of different morphological types of granules. In this study, the microbial compositions of the different granules were analyzed by molecular microbiological techniques: cloning, denaturing gradient

  10. The number of granule cells in rat hippocampus is reduced after chronic mild stress and re-established after chronic escitalopram treatment

    DEFF Research Database (Denmark)

    Jayatissa, Magdalena N; Bisgaard, Christina; West, Mark J

    2008-01-01

    mild stress and chronic escitalopram treatment. Furthermore, we investigated which classes of immature granule cells are affected by stress and targeted by escitalopram. Rats were initially exposed to 2weeks of CMS and 4weeks of escitalopram treatment with concurrent exposure to stress. The behavioral...... changes, indicating a decrease in sensitivity to a reward, were assessed in terms of sucrose consumption. We found a significant 22.4% decrease in the total number of granule cells in the stressed rats. This decrease was reversed in the stressed escitalopram treated rats that responded to the treatment......, but not in the rats that did not respond to escitalopram treatment. These changes were not followed by alterations in the volume of the granule cell layer. We also showed a differential regulation of dentate neurons, in different stages of development, by chronic stress and chronic escitalopram treatment. Our study...

  11. AMP Kinase Activation Alters Oxidant-Induced Stress Granule Assembly by Modulating Cell Signaling and Microtubule Organization.

    Science.gov (United States)

    Mahboubi, Hicham; Koromilas, Antonis E; Stochaj, Ursula

    2016-10-01

    Eukaryotic cells assemble stress granules (SGs) when translation initiation is inhibited. Different cell signaling pathways regulate SG production. Particularly relevant to this process is 5'-AMP-activated protein kinase (AMPK), which functions as a stress sensor and is transiently activated by adverse physiologic conditions. Here, we dissected the role of AMPK for oxidant-induced SG formation. Our studies identified multiple steps of de novo SG assembly that are controlled by the kinase. Single-cell analyses demonstrated that pharmacological AMPK activation prior to stress exposure changed SG properties, because the granules became more abundant and smaller in size. These altered SG characteristics correlated with specific changes in cell survival, cell signaling, cytoskeletal organization, and the abundance of translation initiation factors. Specifically, AMPK activation increased stress-induced eukaryotic initiation factor (eIF) 2α phosphorylation and reduced the concentration of eIF4F complex subunits eIF4G and eIF4E. At the same time, the abundance of histone deacetylase 6 (HDAC6) was diminished. This loss of HDAC6 was accompanied by increased acetylation of α-tubulin on Lys40. Pharmacological studies further confirmed this novel AMPK-HDAC6 interplay and its importance for SG biology. Taken together, we provide mechanistic insights into the regulation of SG formation. We propose that AMPK activation stimulates oxidant-induced SG formation but limits their fusion into larger granules. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  12. Effective biotransformation and detoxification of anthraquinone dye reactive blue 4 by using aerobic bacterial granules.

    Science.gov (United States)

    Chaudhari, Ashvini U; Paul, Dhiraj; Dhotre, Dhiraj; Kodam, Kisan M

    2017-10-01

    Treatment of textile wastewater containing anthraquinone dye is quite a huge challenge due to its complex aromatic structure and toxicity. Present study deals with the degradation and detoxification of anthraquinone dye reactive blue 4 using aerobic bacterial granules. Bacterial granules effectively decolorized reactive blue 4 at wide range of pH (4.0-11.0) and temperature (20-55 °C) as well as decolorized and tolerated high concentration of reactive blue 4 dye upto 1000 mg l -1 with V max 6.16 ± 0.82 mg l -1 h -1 and K m 227 ± 41 mg l -1 . Metagenomics study evaluates important role of Clostridia, Actinobacteria, and Proteobacterial members in biotransformation and tolerance of high concentrations of reactive blue 4 dye. Up-regulation of xenobiotic degradation and environmental information processing pathways during dye exposure signifies their noteworthy role in dye degradation. Biotransformation of dye was confirmed by significant decrease in the values of total suspended solids, biological and chemical oxygen demand. The metabolites formed after biotransformation was characterized by FT-IR and GC-MS analysis. The reactive blue 4 dye was found to be phytotoxic, cytotoxic and genotoxic whereas its biotransformed product were non-toxic. This study comprehensively illustrates that, bacterial aerobic granules can be used for eco-friendly remediation and detoxification of wastewater containing high organic load of anthraquinone dye. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Effect of matrix granulation and wax coating on the dissolution rates ...

    African Journals Online (AJOL)

    disintegrating) granules consisting of paracetamol (drug) and acrylatemethacrylate copolymer, a matrix forming material. The effect of coating the matrix granules with wax on the drug release profiles was also investigated. The objective was to ...

  14. Effect of particle size of granules on some mechanical properties of ...

    African Journals Online (AJOL)

    PRECIOUS

    2009-11-02

    Nov 2, 2009 ... granules on some tablet mechanical properties of paracetamol tablets. Granules ... massing paracetamol powder (200 g) with 20% (w/w) of maize starch mucilage as binder. .... The resulting tablets were stored overnight in a.

  15. Formulation of a poorly water-soluble drug in sustained-release hollow granules with a high viscosity water-soluble polymer using a fluidized bed rotor granulator.

    Science.gov (United States)

    Asada, Takumi; Yoshihara, Naoki; Ochiai, Yasushi; Kimura, Shin-Ichiro; Iwao, Yasunori; Itai, Shigeru

    2018-04-25

    Water-soluble polymers with high viscosity are frequently used in the design of sustained-release formulations of poorly water-soluble drugs to enable complete release of the drug in the gastrointestinal tract. Tablets containing matrix granules with a water-soluble polymer are preferred because tablets are easier to handle and the multiple drug-release units of the matrix granules decreases the influences of the physiological environment on the drug. However, matrix granules with a particle size of over 800 μm sometimes cause a content uniformity problem in the tableting process because of the large particle size. An effective method of manufacturing controlled-release matrix granules with a smaller particle size is desired. The aim of this study was to develop tablets containing matrix granules with a smaller size and good controlled-release properties, using phenytoin as a model poorly water-soluble drug. We adapted the recently developed hollow spherical granule granulation technology, using water-soluble polymers with different viscosities. The prepared granules had an average particle size of 300 μm and sharp particle size distribution (relative width: 0.52-0.64). The values for the particle strength of the granules were 1.86-1.97 N/mm 2 , and the dissolution profiles of the granules were not affected by the tableting process. The dissolution profiles and the blood concentration levels of drug released from the granules depended on the viscosity of the polymer contained in the granules. We succeeded in developing the desired controlled-release granules, and this study should be valuable in the development of sustained-release formulations of poorly water-soluble drugs. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. Absence of diabetes and pancreatic exocrine dysfunction in a transgenic model of carboxyl-ester lipase-MODY (maturity-onset diabetes of the young.

    Directory of Open Access Journals (Sweden)

    Helge Ræder

    Full Text Available CEL-MODY is a monogenic form of diabetes with exocrine pancreatic insufficiency caused by mutations in CARBOXYL-ESTER LIPASE (CEL. The pathogenic processes underlying CEL-MODY are poorly understood, and the global knockout mouse model of the CEL gene (CELKO did not recapitulate the disease. We therefore aimed to create and phenotype a mouse model specifically over-expressing mutated CEL in the pancreas.We established a monotransgenic floxed (flanking LOX sequences mouse line carrying the human CEL mutation c.1686delT and crossed it with an elastase-Cre mouse to derive a bitransgenic mouse line with pancreas-specific over-expression of CEL carrying this disease-associated mutation (TgCEL. Following confirmation of murine pancreatic expression of the human transgene by real-time quantitative PCR, we phenotyped the mouse model fed a normal chow and compared it with mice fed a 60% high fat diet (HFD as well as the effects of short-term and long-term cerulein exposure.Pancreatic exocrine function was normal in TgCEL mice on normal chow as assessed by serum lipid and lipid-soluble vitamin levels, fecal elastase and fecal fat absorption, and the normoglycemic mice exhibited normal pancreatic morphology. On 60% HFD, the mice gained weight to the same extent as controls, had normal pancreatic exocrine function and comparable glucose tolerance even after resuming normal diet and follow up up to 22 months of age. The cerulein-exposed TgCEL mice gained weight and remained glucose tolerant, and there were no detectable mutation-specific differences in serum amylase, islet hormones or the extent of pancreatic tissue inflammation.In this murine model of human CEL-MODY diabetes, we did not detect mutation-specific endocrine or exocrine pancreatic phenotypes, in response to altered diets or exposure to cerulein.

  17. Absence of diabetes and pancreatic exocrine dysfunction in a transgenic model of carboxyl-ester lipase-MODY (maturity-onset diabetes of the young).

    Science.gov (United States)

    Ræder, Helge; Vesterhus, Mette; El Ouaamari, Abdelfattah; Paulo, Joao A; McAllister, Fiona E; Liew, Chong Wee; Hu, Jiang; Kawamori, Dan; Molven, Anders; Gygi, Steven P; Njølstad, Pål R; Kahn, C Ronald; Kulkarni, Rohit N

    2013-01-01

    CEL-MODY is a monogenic form of diabetes with exocrine pancreatic insufficiency caused by mutations in CARBOXYL-ESTER LIPASE (CEL). The pathogenic processes underlying CEL-MODY are poorly understood, and the global knockout mouse model of the CEL gene (CELKO) did not recapitulate the disease. We therefore aimed to create and phenotype a mouse model specifically over-expressing mutated CEL in the pancreas. We established a monotransgenic floxed (flanking LOX sequences) mouse line carrying the human CEL mutation c.1686delT and crossed it with an elastase-Cre mouse to derive a bitransgenic mouse line with pancreas-specific over-expression of CEL carrying this disease-associated mutation (TgCEL). Following confirmation of murine pancreatic expression of the human transgene by real-time quantitative PCR, we phenotyped the mouse model fed a normal chow and compared it with mice fed a 60% high fat diet (HFD) as well as the effects of short-term and long-term cerulein exposure. Pancreatic exocrine function was normal in TgCEL mice on normal chow as assessed by serum lipid and lipid-soluble vitamin levels, fecal elastase and fecal fat absorption, and the normoglycemic mice exhibited normal pancreatic morphology. On 60% HFD, the mice gained weight to the same extent as controls, had normal pancreatic exocrine function and comparable glucose tolerance even after resuming normal diet and follow up up to 22 months of age. The cerulein-exposed TgCEL mice gained weight and remained glucose tolerant, and there were no detectable mutation-specific differences in serum amylase, islet hormones or the extent of pancreatic tissue inflammation. In this murine model of human CEL-MODY diabetes, we did not detect mutation-specific endocrine or exocrine pancreatic phenotypes, in response to altered diets or exposure to cerulein.

  18. A comparison of caspase 3 expression in the endocrine and exocrine parts of the pancreas after cladribine application according to the "leukemic" schema

    Directory of Open Access Journals (Sweden)

    Jasinski Ludwik

    2017-03-01

    Full Text Available The therapeutic effects of the immunosuppressive agent, cladribine, have been demonstrated by its toxicity to cells. However, its effects on healthy cells of the body is poorly understood. The aim of study was, hence, to, firstly, evaluate the morphology of the endocrine and exocrine pancreas after the administration of cladribine according to the "leukemic" schema, and, secondly, to assess its impact on the intensity of apoptosis. The experiment was carried out on female Wistar rats which were placed within the control group KA, and the experimental groups: A and A-bis. In the experimental groups, Cladribine was administered according to the cycle used to treat human hairy cell leukemia. In group A, the material was taken 24 hours after administration of the last dose of the drug, while in group A-bis, this was done after a 4 weeks break. The reaction was assessed to be average in 80% of all cells in group A, and in 64% of all acinar cells in group KA, while in group A-bis, the majority of the exocrine cells demonstrated a lack of immunohistochemical response (72%. Moreover, most endocrine cells (60% in group A-bis revealed a strong reaction, while in Group A, the corresponding figure is a little over 34%. A comparison of the severity of the caspase 3 expression in both the exocrine and endocrine pancreas showed significant differentiation results between the group KA and group A-bis, and between group A and A-bis (p < 0.0001. In can be concluded that endocrine cells are more sensitive to cladribine than are exocrine cells.

  19. Pancreatic mesenchyme regulates epithelial organogenesis throughout development.

    Directory of Open Access Journals (Sweden)

    Limor Landsman

    2011-09-01

    Full Text Available The developing pancreatic epithelium gives rise to all endocrine and exocrine cells of the mature organ. During organogenesis, the epithelial cells receive essential signals from the overlying mesenchyme. Previous studies, focusing on ex vivo tissue explants or complete knockout mice, have identified an important role for the mesenchyme in regulating the expansion of progenitor cells in the early pancreas epithelium. However, due to the lack of genetic tools directing expression specifically to the mesenchyme, the potential roles of this supporting tissue in vivo, especially in guiding later stages of pancreas organogenesis, have not been elucidated. We employed transgenic tools and fetal surgical techniques to ablate mesenchyme via Cre-mediated mesenchymal expression of Diphtheria Toxin (DT at the onset of pancreas formation, and at later developmental stages via in utero injection of DT into transgenic mice expressing the Diphtheria Toxin receptor (DTR in this tissue. Our results demonstrate that mesenchymal cells regulate pancreatic growth and branching at both early and late developmental stages by supporting proliferation of precursors and differentiated cells, respectively. Interestingly, while cell differentiation was not affected, the expansion of both the endocrine and exocrine compartments was equally impaired. To further elucidate signals required for mesenchymal cell function, we eliminated β-catenin signaling and determined that it is a critical pathway in regulating mesenchyme survival and growth. Our study presents the first in vivo evidence that the embryonic mesenchyme provides critical signals to the epithelium throughout pancreas organogenesis. The findings are novel and relevant as they indicate a critical role for the mesenchyme during late expansion of endocrine and exocrine compartments. In addition, our results provide a molecular mechanism for mesenchymal expansion and survival by identifying β-catenin signaling as an

  20. Thermal effects on granules and direct determination of swelling ...

    African Journals Online (AJOL)

    STORAGESEVER

    2009-08-04

    Aug 4, 2009 ... DEA. UAA. Abidjan. Côte d'Ivoire, pp. 25-28. Larrigue S, Alvarez G, Cuvelier G, Flick D (2008). Swelling kinetics of waxy maize and starches at high temperatures and heating rates. Carbohydr. Polym. 73: 148-155. Leach HW, MC Cowen LD, Schoch JJ (1959). Structure of the starch granule swelling and ...

  1. Electron microscopic analysis of the specific granule content of ...

    African Journals Online (AJOL)

    Knowledge about the stimulus for the release of atrial natriuretic peptide (ANP) from human atria is incomplete. Atrial stretch is known to be a stimulus and atrial tachyarrhythmias are thought to be another. The effects of atrial size (by twodimensional echocardiography) and atrial fibrillation on the atrial specific granule ...

  2. Glass foam granulate as growing medium for tomato and cucumber

    NARCIS (Netherlands)

    Blok, C.; Winkel, van A.; Chizhmak, S.

    2011-01-01

    Glass foam granulate was evaluated for use as a horticultural rooting medium with laboratory tests and cultivation experiments. The laboratory tests included moisture characteristics, rehydration rate and pH buffering analyses. Cucumbers and later on tomatoes were propagated in rockwool propagation

  3. ATP storage and uptake by isolated pancreatic zymogen granules

    DEFF Research Database (Denmark)

    Haanes, Kristian Agmund; Novak, Ivana

    2010-01-01

    ATP is released from pancreatic acini in response to cholinergic and hormonal stimulation. The same stimuli cause exocytosis of ZG (zymogen granules) and release of digestive enzymes. The aim of the present study was to determine whether ZG stored ATP and to characterize the uptake mechanism for ...

  4. Effect of Drug Active Substance Particles on Wet Granulation Process.

    Czech Academy of Sciences Publication Activity Database

    Bělohlav, Z.; Břenková, L.; Hanika, Jiří; Durdil, P.; Rapek, P.; Tomášek, V.

    2007-01-01

    Roč. 85, A7 (2007) , s. 974-980 ISSN 0263-8762 Institutional research plan: CEZ:AV0Z40720504 Keywords : wet granulation * control * active substance Subject RIV: CI - Industrial Chemistry, Chemical Engineering Impact factor: 0.837, year: 2007

  5. Measurement of the moisture content of the granulated sugar by ...

    African Journals Online (AJOL)

    AJB SERVER

    2007-01-18

    Jan 18, 2007 ... The moisture content of granulated sugar is a critical parameter for its transformation into cubes. To the best of our ... resolve this, a new method using infrared transphotometry technique based on the attenuation of an infrared ... contribution of other interactions to the attenuation of the incident wave, i.e. ...

  6. Granulated Silica Method for the Fiber Preform Production

    Directory of Open Access Journals (Sweden)

    Sönke Pilz

    2017-07-01

    Full Text Available During the past few years, we have studied the granulated silica method as a versatile and cost effective way of fiber preform production and the sol-gel method. Until now, we have used the sol-gel technology together with an iterative re-melting and milling step in order to produce rare earth or transition metal doped granular material for the granulated silica method. Here, we present that the iterative re-melting (laser-assisted and milling step is no longer needed to reach a high homogeneity. The sol-gel method also offers a high degree of compositional flexibility with respect to dopants; it further facilitates achieving high concentrations, even in cases when several dopants are used. We employed optical active doped sol-gel derived granulate for the fiber core, whereas pure or index-raised granulated silica has been employed for the cladding. Based on the powder-in-tube technique, where silica glass tubes are appropriately filled with these granular materials, fibers has been directly drawn (“fiber rapid prototyping”, or eventually after an additional optional quality enhancing vitrification step. The powder-in-tube technique is also ideally suited for the preparation of microstructured optical fibers.

  7. Iron-based granules in body of bumblebees

    Czech Academy of Sciences Publication Activity Database

    Jandacka, P.; Kasparova, B.; Jirásková, Yvonna; Dedkova, K.; Mamulová-Kutláková, K.; Kukutschová, J.

    2015-01-01

    Roč. 28, č. 1 (2015), s. 89-99 ISSN 0966-0844 R&D Projects: GA ČR(CZ) GAP108/11/1350 Institutional support: RVO:68081723 Keywords : Magnetoreception * Bumblebee * Biomineralisation * Iron granules Subject RIV: BO - Biophysics Impact factor: 2.134, year: 2015

  8. Automation system for production of UO2 granules

    International Nuclear Information System (INIS)

    Swaminathan, N.; Setty, C.R.P.; Banerjee, P.K.; Husnain, G.; Rao, K.C.M.; Satyanarayana, A.

    1990-01-01

    Precompaction of UO 2 powder into slugs and granulation of the slugs were used to be carried out in two different work centres involving manual loading/handling of powder and compacts which resulted in a very high level of air-borne activity. This has been simplified by integrating both the operations into one work centre on both the precompaction presses. In the present system, UO 2 powder is transferred to feed hopper through the use of high vac. feeder. The powder in metered quantities is fed into the shoe by deploying screw feeder driven by a compact hydraulic motor. The die cavity is filled with just the right quantity of powder to prevent spillage. The compacts are pushed on to the granulator through a set of guides mounted on the die platform. The granulated powder is made to pass through Vibro screen for separating the fines before collecting in a replaceable S.S. Container. This container is mounted on the final compacting press by using job crane installed on the press. The replaceable container handling facility drastically cuts down the manual handling of UO 2 granules and also eliminates spillage, air borne activity. The development and fabrication of hydraulically operated screw feeder, feed shoe, replaceable container and the job crane structure etc., were completely carried out at Nuclear Fuel Complex, Hyderabad. Paper deals in detail the design of the system developed, present operational experiences and further improvements planned. (author). 6 figs

  9. Contribution of granule bound starch synthase in kernel modification ...

    African Journals Online (AJOL)

    The role of gbssI and gbssII genes, encoding granule bound starch synthase enzyme I and II, respectively, in quality protein maize (QPM) were studied at different days after pollination (DAP). Total RNA was used for first strand cDNA synthesis using the ImpromIISriptTM reverse transcriptase. No detectable levels of gbssI ...

  10. Population balance modelling of fluidized bed melt granulation: an overview

    NARCIS (Netherlands)

    Tan, H.S.; Goldschmidt, M.J.V.; Boerefijn, R.; Hounslow, M.J.; Salman, A.; Kuipers, J.A.M.

    2005-01-01

    This paper presents an overview of the work undertaken by our group to identify and quantify the rates processes active in fluidized bed melt granulation (FBMG). The process involves the identification and development of physically representative models to mechanistically describe FBMG using both

  11. Measurement of the moisture content of the granulated sugar by ...

    African Journals Online (AJOL)

    The moisture content of granulated sugar is a critical parameter for its transformation into cubes. To the best of our knowledge there is no easy-to-use method for the determination of this parameter. To resolve this, a new method using infrared transphotometry technique based on the attenuation of an infrared radiation ...

  12. Metabolic changes induced by Bushenhouxue Granules on striatum ...

    African Journals Online (AJOL)

    Background: Parkinson's disease is a neurodegenerative disease, while its mechanism is still unclear. Long-term levodopa-based treatment leads to decreased response or loss of response, as well as severe side effects. Our previous study has proved that Bushenhuoxue Granules have effects on Parkinson's disease, but ...

  13. EVIDENCE FOR GRANULATION IN EARLY A-TYPE STARS

    International Nuclear Information System (INIS)

    Kallinger, Thomas; Matthews, Jaymie M.

    2010-01-01

    Stars with spectral types earlier than about F0 on (or close) to the main sequence have long been believed to lack observable surface convection, although evolutionary models of A-type stars do predict very thin surface convective zones. We present evidence for granulation in two δ Scuti stars of spectral type A2: HD 174936 and HD 50844. Recent analyses of space-based CoRoT data revealed up to some 1000 frequencies in the photometry of these stars. The frequencies were interpreted as individual pulsation modes. If true, there must be large numbers of nonradial modes of very high degree l which should suffer cancellation effects in disk-integrated photometry (even of high space-based precision). The p-mode interpretation of all the frequencies in HD 174936 and HD 50844 depends on the assumption of white (frequency-independent) noise. Our independent analyses of the data provide an alternative explanation: most of the peaks in the Fourier spectra are the signature of non-white granulation background noise, and less than about 100 of the frequencies are actual stellar p-modes in each star. We find granulation timescales which are consistent with scaling relations that describe cooler stars with known surface convection. If the granulation interpretation is correct, the hundreds of low-amplitude Fourier peaks reported in recent studies are falsely interpreted as independent pulsation modes and a significantly lower number of frequencies are associated with pulsation, consistent with only modes of low degree.

  14. 21 CFR 520.2520f - Trichlorfon granules.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Trichlorfon granules. 520.2520f Section 520.2520f Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL.... Do not fast horses before or after treatment. Treatment of mares in late pregnancy is not recommended...

  15. Granule-by-granule reconstruction of a sandpile from x-ray microtomography data

    International Nuclear Information System (INIS)

    Seidler, G. T.; Martinez, G.; Seeley, L. H.; Kim, K. H.; Behne, E. A.; Zaranek, S.; Chapman, B. D.; Heald, S. M.; Brewe, D. L.

    2000-01-01

    Mesoscale disordered materials are ubiquitous in industry and in the environment. Any fundamental understanding of the transport and mechanical properties of such materials must follow from a thorough understanding of their structure. However, in the overwhelming majority of cases, experimental characterization of such materials has been limited to first- and second-order structural correlation functions, i.e., the mean filling fraction and the structural autocorrelation function. We report here the successful combination of synchrotron x-ray microtomography and image processing to determine the full three-dimensional real-space structure of a model disordered material, a granular bed of relatively monodisperse glass spheres. Specifically, we determine the center location and the local connectivity of each granule. This complete knowledge of structure can be used to calculate otherwise inaccessible high-order correlation functions. We analyze nematic order parameters for contact bonds to characterize the geometric anisotropy or fabric induced by the sample boundary conditions. Away from the boundaries we find short-range bond orientational order exhibiting characteristics of the underlying polytetrahedral structure

  16. THE EFFECT OF DRY GRANULATION ON THE CONSOLIDATION AND COMPACTION OF CRYSTALLINE LACTOSE

    NARCIS (Netherlands)

    RIEPMA, KA; VROMANS, H; ZUURMAN, K; LERK, CF

    1993-01-01

    The consolidation and compaction properties of granule fractions prepared by dry granulation (slugging) of alpha-lactose monohydrate and roller dried beta-lactose, respectively, were studied. The results showed that the compactibility of the granule fractions was determined by the type of lactose

  17. THE RELATIONSHIP BETWEEN BULK-DENSITY AND COMPACTIBILITY OF LACTOSE GRANULATIONS

    NARCIS (Netherlands)

    ZUURMAN, K; RIEPMA, KA; BOLHUIS, GK; VROMANS, H; LERK, CF

    1994-01-01

    The relationship between the bulk density and the compactibility of lactose granulations was studied. The granulations were prepared from different alpha-lactose monohydrate and roller dried beta-lactose powders by wet granulation, using different techniques with only water as a binder, or by

  18. The consequences of granulate heterogeneity towards breakage and attrition upon fluid-bed drying

    NARCIS (Netherlands)

    Nieuwmeyer, Florentine; Maarschalk, Kees van der Voort; Vromans, Herman

    High-shear granulated lactose granulates were dried in it fluid-bed dryer at various conditions. Granules were characterized by water content and size analysis. It is shown that the drying process is very dynamic in terms of growth and breakage phenomena. Granular size heterogeneity, composition and

  19. TABLETING PROPERTIES OF EXPERIMENTAL AND COMMERCIALLY AVAILABLE LACTOSE GRANULATIONS FOR DIRECT COMPRESSION

    NARCIS (Netherlands)

    BOLHUIS, GK; ZUURMAN, K

    1995-01-01

    Lactose granulations (125-250 mu m) were prepared from two different alpha-lactose monohydrate powders and one roller dried beta-lactose powder respectively, by wet granulation with only water as a binder. As an effect of the granulation process, the flow properties improved, but the compactibility

  20. File list: DNS.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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  1. File list: Pol.Neu.50.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

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  18. File list: ALL.Neu.05.AllAg.Cerebellar_granule_neurons [Chip-atlas[Archive

    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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    Lifescience Database Archive (English)

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  1. Surface Modification of Porous Titanium Granules for Improving Bioactivity.

    Science.gov (United States)

    Karaji, Zahra Gorgin; Houshmand, Behzad; Faghihi, Shahab

    The highly porous titanium granules are currently being used as bone substitute material and for bone tissue augmentation. However, they suffer from weak bone bonding ability. The aim of this study was to create a nanostructured surface oxide layer on irregularly shaped titanium granules to improve their bioactivity. This could be achieved using optimized electrochemical anodic oxidation (anodizing) and heat treatment processes. The anodizing process was done in an ethylene glycol-based electrolyte at an optimized condition of 60 V for 3 hours. The anodized granules were subsequently annealed at 450°C for 1 hour. Scanning electron microscopy (SEM), energy-dispersive x-ray spectroscopy (EDS), and x-ray diffraction (XRD) were used to characterize the surface structure and morphology of the granules. The in vitro bioactivity of the samples was evaluated by immersion of specimens in simulated body fluid (SBF) for 1, 2, and 3 weeks. The human osteoblastic sarcoma cell line, MG63, was used to evaluate cell viability on the samples using dimethylthiazol-diphenyl tetrazolium bromide (MTT) assay. The results demonstrated the formation of amorphous nanostructured titanium oxide after anodizing, which transformed to crystalline anatase and rutile phases upon heat treatment. After immersion in SBF, spherical aggregates of amorphous calcium phosphate were formed on the surface of the anodized sample, which turned into crystalline hydroxyapatite on the surface of the anodized annealed sample. No cytotoxicity was detected among the samples. It is suggested that anodic oxidation followed by heat treatment could be used as an effective surface treatment procedure to improve bioactivity of titanium granules implemented for bone tissue repair and augmentation.

  2. Magnetic resonance microscopy of iron transport in methanogenic granules

    Science.gov (United States)

    Bartacek, Jan; Vergeldt, Frank J.; Gerkema, Edo; Jenicek, Pavel; Lens, Piet N. L.; Van As, Henk

    2009-10-01

    Interactions between anaerobic biofilms and heavy metals such as iron, cobalt or nickel are largely unknown. Magnetic resonance imaging (MRI) is a non-invasive method that allows in situ studies of metal transport within biofilm matrixes. The present study investigates quantitatively the penetration of iron (1.75 mM) bound to ethylenediaminetetraacetate (EDTA) into the methanogenic granules (spherical biofilm). A spatial resolution of 109 × 109 × 218 μm 3 and a temporal resolution of 11 min are achieved with 3D Turbo Spin Echo (TSE) measurements. The longitudinal relaxivity, i.e. the slope the dependence of the relaxation rate (1/ T1) on the concentration of paramagnetic metal ions, was used to measure temporal changes in iron concentration in the methanogenic granules. It took up to 300 min for the iron-EDTA complex ([FeEDTA] 2-) to penetrate into the methanogenic granules (3-4 mm in diameter). The diffusion was equally fast in all directions with irregularities such as diffusion-facilitating channels and diffusion-resistant zones. Despite these irregularities, the overall process could be modeled using Fick's equations for diffusion in a sphere, because immobilization of [FeEDTA] 2- in the granular matrix (or the presence of a reactive barrier) was not observed. The effective diffusion coefficient ( D ejf) of [FeEDTA] 2- was found to be 2.8 × 10 -11 m 2 s -1, i.e. approximately 4% of D ejf of [FeEDTA] 2- in water. The Fickian model did not correspond to the processes taking place in the core of the granule (3-5% of the total volume of the granule), where up to 25% over-saturation by iron (compare to the concentration in the bulk solution) occurred.

  3. GRANULATION AND BRIQUETTING OF SOLID PRODUCTS FROM FLUE GAS DESULFURIZATION

    Directory of Open Access Journals (Sweden)

    Jan J. Hycnar

    2015-11-01

    Full Text Available Most flue gas desulfurization products can be characterized by significant solubility in water and dusting in dry state. These characteristics can cause a considerable pollution of air, water, and soil. Among many approaches to utilization of this waste, the process of agglomeration using granulation or briquetting has proved very effective. Using desulfurization products a new material of aggregate characteristics has been acquired, and this material is resistant to water and wind erosion as well as to the conditions of transportation and storage. The paper presents the results of industrial trials granulation and briquetting of calcium desulphurization products. The granulation of a mixture of phosphogypsum used with fly ash (in the share 1:5. The resulting granules characterized by a compressive strength of 41.6 MPa, the damping resistance of 70% and 14.2% abrasion. The granulate was used for the production of cement mix. The produced concrete mortar have a longer setting and hardening time, as compared to the traditional ash and gypsum mortar, and have a higher or comparable flexural and compressive strength during hardening. Briquetting trials made of a product called synthetic gypsum or rea-gypsum both in pure form and with the addition of 5% and 10% of the limestone dust. Briquettes have a high initial strength and resistance to abrasion. The values ​​of these parameters increased after 72 hours of seasoning. It was found that higher hardiness of briquettes with rea-gypsum was obtained with the impact of atmospheric conditions and higher resistance to elution of water-soluble components in comparison to ash briquettes.

  4. Cold experiments on ligament formation for blast furnace slag granulation

    International Nuclear Information System (INIS)

    Liu Junxiang; Yu Qingbo; Li Peng; Du Wenya

    2012-01-01

    Rotary cup atomization for molten slag granulation is an attractive alternative to water quenching. However, the mechanism of disintegration of molten slag must be assessed. In the present study, a glycerol/water mixture was substituted for molten slag, and the mechanism of ligament formation in a rotary cup was investigated using photos taken by a high-speed camera. The effects of the angular speed and inner depth of the rotary cup on ligament disintegration was investigated. The results showed that one state of disintegration may transform into another state as the angular speed of the rotary cup increases at a given liquid flow rate. During ligament formation, the number of ligaments increased with an increase in the angular speed of the rotary cup, and a decrease in the diameter of ligament and liquid drop was observed. Moreover, the initial point of disintegration of the ligament moved to the lip of the rotary cup as the angular speed increased. An equation describing the relationship between the diameter of the liquid drop and various factors was used to predict the diameter of the liquid drop. A rotary cup with an inner depth of 30 mm was the best choice for granulation. The results of the present study will be useful for designing devices used in molten slag granulation. - Highlights: ►The results can be used in the granulation of molten blast furnace slag. ► The three different states of disintegration occur as the angular speed of rotary cup increases. ► The mechanism of ligament disintegration is analyzed. ► Eq. can be used to predict the diameter of liquid drop. ► A rotary cup with an inner depth of 30 mm is optimal for granulation.

  5. Combination of ciclopirox olamine and sphingosine-1-phosphate as granulation enhancer in diabetic wounds.

    Science.gov (United States)

    Lim, Natalie Sheng Jie; Sham, Adeline; Chee, Stella Min Ling; Chan, Casey; Raghunath, Michael

    2016-09-01

    Granulation tissue formation requires a robust angiogenic response. As granulation tissue develops, collagen fibers are deposited and compacted. Forces generated in the wake of this process drive wound contraction to reduce the wound area. In diabetics, both angiogenesis and wound contraction are diminished leading to impaired wound healing. To emulate this pathology and to address it pharmacologically, we developed a wound healing model in the diabetic Zucker fatty rat and tested a topical proangiogenic strategy combining antifungal agent ciclopirox olamine (CPX) and lysophospholipid sphingosine-1-phosphate (S1P) to promote diabetic wound closure. In vitro, we demonstrated that CPX + S1P up-regulates a crucial driver of angiogenesis, hypoxia-inducible factor-1, in endothelial cells. Injection of CPX + S1P into subcutaneously implanted sponges in experimental rats showed, in an additive manner, a fivefold increased endothelial infiltration and lectin-perfused vessel length. We developed a splinted diabetic rodent model to achieve low wound contraction rates that are characteristic for the healing mode of diabetic ulcers in humans. We discovered specific dorsal sites that allowed for incremental full-thickness excisional wound depths from 1 mm (superficial) to 3 mm (deep). This enabled us to bring down wound contraction from 51% in superficial wounds to 8% in deep wounds. While the effects of topical gel treatment of CPX + S1P were masked by the rodent-characteristic dominant contraction in superficial wounds, they became clearly evident in deep diabetic wounds. Here, a fivefold increase of functional large vessels resulted in accelerated granulation tissue formulation, accompanied by a 40% increase of compacted thick collagen fibers. This was associated with substantially reduced matrix metalloproteinase-3 and -13 expression. These findings translated into a fivefold increase in granulation-driven contraction, promoting diabetic wound closure. With CPX

  6. High resolution of heterogeneity among human neutrophil granules: physical, biochemical, and ultrastructural properties of isolated fractions.

    Science.gov (United States)

    Rice, W G; Kinkade, J M; Parmley, R T

    1986-08-01

    Previous studies on the fractionation of human neutrophil granules have identified two major populations: myeloperoxidase (MPO)-containing azurophil, or primary, granules and MPO-deficient specific, or secondary, granules. Peripheral blood neutrophils from individual donors were lysed in sucrose-free media by either hypotonic shock or nitrogen cavitation. Using a novel two-gradient Percoll density centrifugation system, the granule-rich postnuclear supernatant was rapidly (ten minutes) and reproducibly resolved into 13 granule fractions (L1 through L8 and H1 through H5). Granule flotation and recentrifugation experiments on both continuous, self-generated and multiple-step gradients using individual and mixed isolated fractions demonstrated that the banding patterns were isopycnic and nonartifactual. Isolated granules were intact based on the findings that biochemical latency of several granule enzymes was greater than 95%, and thin-sectioned electron micrographs demonstrated intact granule profiles. Biochemical analyses of the granule marker proteins MPO, beta-glucuronidase, lysozyme, and lactoferrin indicated that a number of the fractions were related to the major azurophil and specific granule populations. Lactoferrin was found in ten of 13 fractions (L1 through L8, H1 to H2), whereas MPO was found in every fraction. Consistent with these biochemical data, all fractions exhibited varying degrees of heterogeneity based on ultrastructural morphology and cytochemistry, including diaminobenzidine (DAB) reactivity for peroxidase and periodate-thiocarbohydrazide-silver proteinate (PA-TCH-SP) staining for complex glycoconjugates. A variable but significant percentage (23% to 70%) of the granules in fractions L1 through L8 and H1 and H2 showed DAB reactivity, while about 90% of the granules in fractions H3 through H5 were peroxidase positive. These results demonstrated that DAB-reactive granules spanned the entire range of granule size and density. Ultrastructural PA

  7. Clarithromycin highly-loaded gastro-floating fine granules prepared by high-shear melt granulation can enhance the efficacy of Helicobacter pylori eradication.

    Science.gov (United States)

    Aoki, Hajime; Iwao, Yasunori; Mizoguchi, Midori; Noguchi, Shuji; Itai, Shigeru

    2015-05-01

    In an effort to develop a new gastro-retentive drug delivery system (GRDDS) without a large amount of additives, 75% clarithromycin (CAM) loaded fine granules were prepared with three different hydrophobic binders by high-shear melt granulation and their properties were evaluated. Granules containing the higher hydrophobic binder showed sustained drug release and were able to float over 24h. The synchrotron X-ray CT measurement indicated that both the high hydrophobicity of the binder and the void space inside the granules might be involved in their buoyancy. In an in vivo experiment, the floating granules more effectively eradicated Helicobacter pylori than a CAM suspension by remaining in the stomach for a longer period. In short, CAM highly-loaded gastro-floating fine granules can enhance the eradication efficiency of H. pylori compared with CAM alone. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. FMRP Associates with Cytoplasmic Granules at the Onset of Meiosis in the Human Oocyte.

    Directory of Open Access Journals (Sweden)

    Roseanne Rosario

    Full Text Available Germ cell development and primordial follicle formation during fetal life is critical in establishing the pool of oocytes that subsequently determines the reproductive lifespan of women. Fragile X-associated primary ovarian insufficiency (FXPOI is caused by inheritance of the FMR1 premutation allele and approximately 20% of women with the premutation allele develop ovarian dysfunction and premature ovarian insufficiency. However, the underlying disease mechanism remains obscure, and a potential role of FMRP in human ovarian development has not been explored. We have characterised the expression of FMR1 and FMRP in the human fetal ovary at the time of germ cell entry into meiosis through to primordial follicle formation. FMRP expression is exclusively in germ cells in the human fetal ovary. Increased FMRP expression in germ cells coincides with the loss of pluripotency-associated protein expression, and entry into meiosis is associated with FMRP granulation. In addition, we have uncovered FMRP association with components of P-bodies and stress granules, suggesting it may have a role in mRNA metabolism at the time of onset of meiosis. Therefore, this data support the hypothesis that FMRP plays a role regulating mRNAs during pivotal maturational processes in fetal germ cells, and ovarian dysfunction resulting from FMR1 premutation may have its origins during these stages of oocyte development.

  9. Fragile X protein mitigates TDP-43 toxicity by remodeling RNA granules and restoring translation.

    Science.gov (United States)

    Coyne, Alyssa N; Yamada, Shizuka B; Siddegowda, Bhavani Bagevalu; Estes, Patricia S; Zaepfel, Benjamin L; Johannesmeyer, Jeffrey S; Lockwood, Donovan B; Pham, Linh T; Hart, Michael P; Cassel, Joel A; Freibaum, Brian; Boehringer, Ashley V; Taylor, J Paul; Reitz, Allen B; Gitler, Aaron D; Zarnescu, Daniela C

    2015-12-15

    RNA dysregulation is a newly recognized disease mechanism in amyotrophic lateral sclerosis (ALS). Here we identify Drosophila fragile X mental retardation protein (dFMRP) as a robust genetic modifier of TDP-43-dependent toxicity in a Drosophila model of ALS. We find that dFMRP overexpression (dFMRP OE) mitigates TDP-43 dependent locomotor defects and reduced lifespan in Drosophila. TDP-43 and FMRP form a complex in flies and human cells. In motor neurons, TDP-43 expression increases the association of dFMRP with stress granules and colocalizes with polyA binding protein in a variant-dependent manner. Furthermore, dFMRP dosage modulates TDP-43 solubility and molecular mobility with overexpression of dFMRP resulting in a significant reduction of TDP-43 in the aggregate fraction. Polysome fractionation experiments indicate that dFMRP OE also relieves the translation inhibition of futsch mRNA, a TDP-43 target mRNA, which regulates neuromuscular synapse architecture. Restoration of futsch translation by dFMRP OE mitigates Futsch-dependent morphological phenotypes at the neuromuscular junction including synaptic size and presence of satellite boutons. Our data suggest a model whereby dFMRP is neuroprotective by remodeling TDP-43 containing RNA granules, reducing aggregation and restoring the translation of specific mRNAs in motor neurons. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  10. LXR agonist rescued the deficit in the proliferation of the cerebellar granule cells induced by dexamethasone

    Energy Technology Data Exchange (ETDEWEB)

    Bian, Xuting; Zhong, Hongyu; Li, Fen; Cai, Yulong; Li, Xin; Wang, Lian; Fan, Xiaotang, E-mail: fanxiaotang2005@163.com

    2016-09-02

    Dexamethasone (DEX) exposure during early postnatal life produces permanent neuromotor and intellectual deficits and stunts cerebellar growth. The liver X receptor (LXR) plays important roles in CNS development. However, the effects of LXR on the DEX-mediated impairment of cerebellar development remain undetermined. Thus, mice were pretreated with LXR agonist TO901317 (TO) and were later exposed to DEX to evaluate its protective effects on DEX-mediated deficit during cerebellar development. The results showed that an acute exposure of DEX on postnatal day 7 resulted in a significant impairment in cerebellar development and decreased the proliferation of granule neuron precursors in the external granule layer of cerebellum. This effect was attenuated by pretreatment with TO. We further found that the decrease in the proliferation caused by DEX occurred via up-regulation of glucocorticoid receptor and p27kip1, which could be partially prevented by LXR agonist pretreatment. Overall, our results suggest that LXR agonist pretreatment could protect against DEX-induced deficits in cerebellar development in postnatal mice and may thus be perspective recruited to counteract such GC side effects.

  11. LXR agonist rescued the deficit in the proliferation of the cerebellar granule cells induced by dexamethasone

    International Nuclear Information System (INIS)

    Bian, Xuting; Zhong, Hongyu; Li, Fen; Cai, Yulong; Li, Xin; Wang, Lian; Fan, Xiaotang

    2016-01-01

    Dexamethasone (DEX) exposure during early postnatal life produces permanent neuromotor and intellectual deficits and stunts cerebellar growth. The liver X receptor (LXR) plays important roles in CNS development. However, the effects of LXR on the DEX-mediated impairment of cerebellar development remain undetermined. Thus, mice were pretreated with LXR agonist TO901317 (TO) and were later exposed to DEX to evaluate its protective effects on DEX-mediated deficit during cerebellar development. The results showed that an acute exposure of DEX on postnatal day 7 resulted in a significant impairment in cerebellar development and decreased the proliferation of granule neuron precursors in the external granule layer of cerebellum. This effect was attenuated by pretreatment with TO. We further found that the decrease in the proliferation caused by DEX occurred via up-regulation of glucocorticoid receptor and p27kip1, which could be partially prevented by LXR agonist pretreatment. Overall, our results suggest that LXR agonist pretreatment could protect against DEX-induced deficits in cerebellar development in postnatal mice and may thus be perspective recruited to counteract such GC side effects.

  12. Impact of fill-level in twin-screw granulation on critical quality attributes of granules and tablets.

    Science.gov (United States)

    Meier, Robin; Moll, Klaus-Peter; Krumme, Markus; Kleinebudde, Peter

    2017-06-01

    In a previous study a change of the fill-level in the barrel exerted a huge influence on the twin-screw granulation (TSG) process of a high drug loaded, simplified formulation. The present work investigated this influence systematically. The specific feed load (SFL) indicating the mass per revolution as surrogate parameter for the fill-level was applied and the correlation to the real volumetric fill level of an extruder could be demonstrated by a newly developed method. A design of experiments was conducted to examine the combined influence of SFL and screw speed on the process and on critical quality attributes of granules and tablets. The same formulation was granulated at constant liquid level with the same screw configuration and led to distinctively different results by only changing the fill-level and the screw speed. The power consumption of the extruder increased at higher SFLs with hardly any influence of screw speed. At low SFL the median residence time was mainly fill-level dependent and at higher SFL mainly screw speed dependent. Optimal values for the product characteristics were found at medium values for the SFL. Granule size distributions shifted from mono-modal and narrow shape to broader and even bimodal distributions of larger median granule sizes, when exceeding or falling below a certain fill-level. Deviating from the optimum fill-level, tensile strength of tablets decreased by about 25% and disintegration times of tablets increased for more than one third. At low fill-levels, material accumulation in front of the kneading zone was detected by pressure measurements and was assumed to be responsible for the unfavored product performance. At high fill-levels, granule consolidation due to higher propensity of contact with the result of higher material temperature was accounted for inferior product performance. The fill-level was found to be an important factor in assessment and development of twin-screw granulation processes as it impacted

  13. Decreased α-cell mass and early structural alterations of the exocrine pancreas in patients with type 1 diabetes: An analysis based on the nPOD repository.

    Directory of Open Access Journals (Sweden)

    Fidéline Bonnet-Serrano

    Full Text Available Abnormal glucagon secretion and functional alterations of the exocrine pancreas have been described in patients with type 1 diabetes (T1D, but their respective anatomical substrata have seldom been investigated. Our aim was to develop an automated morphometric analysis process to characterize the anatomy of α-cell and exocrine pancreas in patients with T1D, using the publicly available slides of the Network for Pancreatic Organ Donors (nPOD.The ratio of β- and α-cell area to total tissue area were quantified in 75 patients with T1D (thereafter patients and 66 control subjects (thereafter controls, on 2 insulin-stained and 4 glucagon-stained slides from both the head and the tail of the pancreas. The β- and α-cell masses were calculated in the 66 patients and the 50 controls for which the pancreas weight was available. Non-exocrine-non-endocrine tissue area (i.e. non-acinar, non-insular tissue to total tissue area ratio was evaluated on both insulin- and glucagon-stained slides. Results were expressed as mean ±SD.An automated quantification method was set up using the R software and was validated by quantification of β-cell mass, a well characterized parameter. β-cell mass was 29.6±112 mg in patients and 628 ±717 mg in controls (p<0.0001. α-cell mass was 181±176 mg in patients and 349 ±241mg in controls (p<0.0001. Non-exocrine-non-endocrine area to total tissue area ratio was 39±9% in patients and 29± 10% in controls (p<0.0001 and increased with age in both groups, with no correlation with diabetes duration in patients.The absolute α-cell mass was lower in patients compared to controls, in proportion to the decrease in pancreas weight observed in patients. Non-exocrine-non-endocrine area to total tissue area ratio increased with age in both groups but was higher in patients at all ages.

  14. Risk factors of exocrine and endocrine pancreatic insufficiency after pancreatic resection: A multi-center prospective study.

    Science.gov (United States)

    Maignan, A; Ouaïssi, M; Turrini, O; Regenet, N; Loundou, A; Louis, G; Moutardier, V; Dahan, L; Pirrò, N; Sastre, B; Delpero, J-R; Sielezneff, I

    2018-01-26

    Management of functional consequences after pancreatic resection has become a new therapeutic challenge. The goal of our study is to evaluate the risk factors for exocrine (ExoPI) and endocrine (EndoPI) pancreatic insufficiency after pancreatic surgery and to establish a predictive model for their onset. Between January 1, 2014 and June 19, 2015, 91 consecutive patients undergoing pancreatoduodenectomy (PD) or left pancreatectomy (LP) (72% and 28%, respectively) were followed prospectively. ExoPI was defined as fecal elastase content126mg/dL or aggravation of preexisting diabetes. The volume of residual pancreas was measured according to the same principles as liver volumetry. The ExoPI and EndoPI rates at 6 months were 75.9% and 30.8%, respectively. The rate of ExoPI after PD was statistically significantly higher than after LP (98% vs. 21%; Ppancreatic volume less than 39.5% was predictive of ExoPI. ExoPI occurs quasi-systematically after PD irrespective of the reconstruction scheme. The rate of EndoPI did not differ between PD and LP. Copyright © 2017. Published by Elsevier Masson SAS.

  15. Exocrine Gland-Secreting Peptide 1 Is a Key Chemosensory Signal Responsible for the Bruce Effect in Mice.

    Science.gov (United States)

    Hattori, Tatsuya; Osakada, Takuya; Masaoka, Takuto; Ooyama, Rumi; Horio, Nao; Mogi, Kazutaka; Nagasawa, Miho; Haga-Yamanaka, Sachiko; Touhara, Kazushige; Kikusui, Takefumi

    2017-10-23

    The Bruce effect refers to pregnancy termination in recently pregnant female rodents upon exposure to unfamiliar males [1]. This event occurs in specific combinations of laboratory mouse strains via the vomeronasal system [2, 3]; however, the responsible chemosensory signals have not been fully identified. Here we demonstrate that the male pheromone exocrine gland-secreting peptide 1 (ESP1) is one of the key factors that causes pregnancy block. Female mice exhibited high pregnancy failure rates upon encountering males that secreted different levels of ESP1 compared to the mated male. The effect was not observed in mice that lacked the ESP1 receptor, V2Rp5, which is expressed in vomeronasal sensory neurons. Prolactin surges in the blood after mating, which are essential for maintaining luteal function, were suppressed by ESP1 exposure, suggesting that a neuroendocrine mechanism underlies ESP1-mediated pregnancy failure. The single peptide pheromone ESP1 conveys not only maleness to promote female receptivity but also the males' characteristics to facilitate memorization of the mating partner. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Shotgun proteomics deciphered age/division of labor-related functional specification of three honeybee (Apis mellifera L.) exocrine glands.

    Science.gov (United States)

    Fujita, Toshiyuki; Kozuka-Hata, Hiroko; Hori, Yutaro; Takeuchi, Jun; Kubo, Takeo; Oyama, Masaaki

    2018-01-01

    The honeybee (Apis mellifera L.) uses various chemical signals produced by the worker exocrine glands to maintain the functioning of its colony. The roles of worker postcerebral glands (PcGs), thoracic glands (TGs), and mandibular glands (MGs) and the functional changes they undergo according to the division of labor from nursing to foraging are not as well studied. To comprehensively characterize the molecular roles of these glands in workers and their changes according to the division of labor of workers, we analyzed the proteomes of PcGs, TGs, and MGs from nurse bees and foragers using shotgun proteomics technology. We identified approximately 2000 proteins from each of the nurse bee or forager glands and highlighted the features of these glands at the molecular level by semiquantitative enrichment analyses of frequently detected, gland-selective, and labor-selective proteins. First, we found the high potential to produce lipids in PcGs and MGs, suggesting their relation to pheromone production. Second, we also found the proton pumps abundant in TGs and propose some transporters possibly related to the saliva production. Finally, our data unveiled candidate enzymes involved in labor-dependent acid production in MGs.

  17. Statistical properties of solar granulation from the SOUP instrument on Spacelab 2

    International Nuclear Information System (INIS)

    Topka, K.; Title, A.; Tarbell, T.; Ferguson, S.; Shine, R.

    1988-01-01

    The Solar Optical Universal Polarimeter (SOUP) on Spacelab 2 collected movies of solar granulation completely free from atmospheric blurring, and are not degraded by pointint jitter (the pointing stability was 0.003 sec root mean square). The movies illustrate that the solar five minute oscillation has a major role in the appearance of solar granulation and that exploding granules are a common feature of the granule evolution. Using 3-D Fourier filtering techniques the oscillations were removed and it was demonstrated that the autocorrelation lifetime of granulation is a factor of two greater in magnetic field regions than in field-free quiet sun. Horizontal velocities were measured and flow patterns were observed on the scale of meso- and super granulation. In quiet regions the mean flow velocity is 370 m/s while in the magnetic regions it is about 125 m/s. It was also found that the root mean square (RMS) fluctuating horizonal velocity field is substantially greater in quiet sun than in strong magnetic field regions. By superimposing the location of exploding granules on the average flow maps it was found that they appear almost exclusively in the center of mesogranulation size flow cells. Because of the nonuniformity of the distribution of exploding granules, the evolution of the granulation pattern in mesogranule cell centers and boundaries differs fundamentally. It is clear from this study there is neither a typical granule nor a typical granule evolution

  18. Statistical properties of solar granulation from the SOUP instrument on Spacelab 2

    Science.gov (United States)

    Topka, K.; Title, A.; Tarbell, T.; Ferguson, S.; Shine, R.

    1988-11-01

    The Solar Optical Universal Polarimeter (SOUP) on Spacelab 2 collected movies of solar granulation completely free from atmospheric blurring, and are not degraded by pointint jitter (the pointing stability was 0.003 sec root mean square). The movies illustrate that the solar five minute oscillation has a major role in the appearance of solar granulation and that exploding granules are a common feature of the granule evolution. Using 3-D Fourier filtering techniques the oscillations were removed and it was demonstrated that the autocorrelation lifetime of granulation is a factor of two greater in magnetic field regions than in field-free quiet sun. Horizontal velocities were measured and flow patterns were observed on the scale of meso- and super granulation. In quiet regions the mean flow velocity is 370 m/s while in the magnetic regions it is about 125 m/s. It was also found that the root mean square (RMS) fluctuating horizonal velocity field is substantially greater in quiet sun than in strong magnetic field regions. By superimposing the location of exploding granules on the average flow maps it was found that they appear almost exclusively in the center of mesogranulation size flow cells. Because of the nonuniformity of the distribution of exploding granules, the evolution of the granulation pattern in mesogranule cell centers and boundaries differs fundamentally. It is clear from this study there is neither a typical granule nor a typical granule evolution.

  19. Maintained LTP and Memory Are Lost by Zn2+ Influx into Dentate Granule Cells, but Not Ca2+ Influx.

    Science.gov (United States)

    Takeda, Atsushi; Tamano, Haruna; Hisatsune, Marie; Murakami, Taku; Nakada, Hiroyuki; Fujii, Hiroaki

    2018-02-01

    The idea that maintained LTP and memory are lost by either increase in intracellular Zn 2+ in dentate granule cells or increase in intracellular Ca 2+ was examined to clarify significance of the increases induced by excess synapse excitation. Both maintained LTP and space memory were impaired by injection of high K + into the dentate gyrus, but rescued by co-injection of CaEDTA, which blocked high K + -induced increase in intracellular Zn 2+ but not high K + -induced increase in intracellular Ca 2+ . High K + -induced disturbances of LTP and intracellular Zn 2+ are rescued by co-injection of 6-cyano-7-nitroquinoxakine-2,3-dione, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor antagonist, but not by co-injection of blockers of NMDA receptors, metabotropic glutamate receptors, and voltage-dependent calcium channels. Furthermore, AMPA impaired maintained LTP and the impairment was also rescued by co-injection of CaEDTA, which blocked increase in intracellular Zn 2+ , but not increase in intracellular Ca 2+ . NMDA and glucocorticoid, which induced Zn 2+ release from the internal stores, did not impair maintained LTP. The present study indicates that increase in Zn 2+ influx into dentate granule cells through AMPA receptors loses maintained LTP and memory. Regulation of Zn 2+ influx into dentate granule cells is more critical for not only memory acquisition but also memory retention than that of Ca 2+ influx.

  20. Behavior of hollow balls containing granules bouncing repeatedly off the ground

    Science.gov (United States)

    Hu, Min; Mu, Qing-song; Luo, Ning; Li, Gang; Peng, Ning-bo

    2013-07-01

    An experimental study of the behavior of hollow balls filled with some granules (mung beans or millets) bouncing repeatedly off a static flat horizontal surface is presented. We observed that the bounce number of the ball is limited and decreases regularly with an increasing number of granules. Moreover, for two balls containing a different kind of granules, their bounce numbers are basically equal when the two balls have the same mass of granules. While there is no clear relationship between the first rebound height of one ball and the number of granules, there appears an exponential decay of the second rebound height with an increase of the granule number. Furthermore, a two-dimensional numerical model has been created to find out the law of the ball's rebound height and the dissipation law of the granule nested system. A generalized prediction equation to reasonably explain the law of the bounce number has also been proposed.

  1. The converse magnetoelectric coupling in asymmetric granule/matrix composite film with Ni/PZT component

    Science.gov (United States)

    Chen, Bo; Su, Ning-Ning; Cui, Wen-Li; Yan, Shi-Nong

    2018-04-01

    In this work, a type of asymmetric granule/matrix composite film is designed, where the Ni granule is dispersed in PZT matrix, meanwhile the top and bottom electrode is constituted by Au and SRO respectively. Predicted through the electrostatic screening model and mean field approximation, considerable electrostatic charge is induced on Ni granule surface by ferroelectric PZT polarization. Predicted through the spin splitting model and spherical shell approximation, both the magnetization and magnetic anisotropy of Ni granule are modulated by ferroelectric PZT polarization. As the volume fraction of Ni granule is increased, the electric modulation of magnetization and magnetic anisotropy is reduced and enhanced respectively. As the dimension of granule/matrix composite is varied, such modulation is retained. Due to the large area-volume ratio of nano-granule, this work benefits to realize the converse magnetoelectric coupling in nanoscale.

  2. MICROMORPHOLOGICAL STUDIES OF STARCH GRANULES IN SELECTED PROCESSED INDIGENOUS FLOUR OF SOUTH WESTERN NIGERIA

    Directory of Open Access Journals (Sweden)

    Adeniyi A. JAYEOLA

    2013-06-01

    Full Text Available Starch granules of yam stem tubers, plantain fruits and cassava root tubers were studied using the light microscope and then compared. Yam and plantain, both monocotyledons, had morphologically similar granules between locations, being mostly oval in shape while the granules of cassava, a dicot, were predominantly globular but varied between locations. Differences in processing methods between locations might be responsible for the observed variation in cassava granules. There is a suggestion that starch granule morphology might follow lineages in a broad sense. The unique micromorphology of cassava starch granule could make it easily detectable when adulterated, substituted or contaminated with yam or plantain granules and this could provide a cost effective clue in forensic determination.

  3. GRANULATION TRIALS OF WASTE THE DUST SILICON CARBIDE FOR UTILIZATION IN METALLURGY

    Directory of Open Access Journals (Sweden)

    Gabriel Borowski

    2016-09-01

    Full Text Available The article presents the results of laboratory granulation tests of dust silicon carbide and the results of research on the selection of the binder and the properties of the granules obtained. The research material was a waste of the silicon carbide powder with a high fragmentation, mixed with a cement or an organic modified starch specimen. Six tests were performed in a disc granulator with 100 cm in diameter. In each series of trial specified: the type and share of the binder, the diameter of the granules, tenderness, type of structure and mechanical properties. Good granules of silicon carbide obtained with the addition of cement binder with 4% of the mass fraction and at least 24 hours of seasoning. The binder should be added twice by powdering, first in a stirred granulator, and again after manufacture. It was found that the resulting granules may be used as a replacement of ferrosilicon in the process of steelmaking.

  4. Self-organizing of critical state in granulated superconductors

    International Nuclear Information System (INIS)

    Ginzburg, S.L.; Savitskaya, N.E.

    2000-01-01

    Critical state in granulated superconductors was studied on the basis of two mathematical models - the system of differential equations for calibration and invariant difference of phases and a simplified model describing the system of associated images and equivalent to the standard models to study self-organizing criticality. The critical state of granulated superconductors in all studied cases was shown to be self-organized. Besides, it is shown that the applied models are practically equivalent ones, that is they both show similar critical behavior and lead to coincidence of noncritical phenomena. For the first time one showed that the occurrence of self-organized critically within the system of nonlinear differential equations and its equivalence to self-organized critically in the standard models [ru

  5. Block-based approach to modelling of granulated fertilizers' quality

    DEFF Research Database (Denmark)

    Kohonen, J.; Reinikainen, S. P.; Høskuldsson, Agnar

    2009-01-01

    be defined through testing the flow rate with, e.g., seed drill. Besides the chemical composition, flowability can be considered as one of the most important characteristics. There are numerous factors affecting the flowability of a granulated fertilizer, several of them related to the particle size......Fertilizer manufacturing is a customer-driven industry, where the quality of a product is a key factor in order to survive the competition. However, measuring the most important feature with granulated fertilizers, flowability, is tedious, time-consuming and thus expensive. Flowability can...... size distribution. The goals are to find a reliable model for flowability using this data and to find the most important variables and to identify the effect of blocks to the quality....

  6. Spray Drying Processing: granules production and drying kinetics of droplets

    International Nuclear Information System (INIS)

    Mondragon, R.; Julia, J. E.; Barba, A.; Jarque, J. C.

    2013-01-01

    Spray drying is a unit operation very common in many industrial processes. For each particular application, the resulting granulated material must possess determined properties that depend on the conditions in which the spray drying processing has been carried out, and whose dependence must be known in order to optimize the quality of the material obtained. The large number of variables that influence on the processes of matter and energy transfer and on the formation of granular material has required a detailed analysis of the drying process. Over the years there have been many studies on the spray drying processing of all kind of materials and the influence of process variables on the drying kinetics of the granulated material properties obtained. This article lists the most important works published for both the spray drying processing and the drying of individual droplets, as well as studies aimed at modeling the drying kinetics of drops. (Author)

  7. Contaminated fluid filtration plant using pneumatically renewable granulated material

    International Nuclear Information System (INIS)

    Lucas, J.-C.; Messirejean, Pierre.

    1980-01-01

    This invention concerns a plant for the filtration of a contaminated fluid flow using a granulated material capable of absorbing or adsorbing the contaminants. This plant includes a filtration box within which there is at least one appreciably vertical filtering bed filled with the material and crossed by the fluid flow, loading and discharge compartments respectively located at the top and bottom of the box, each in communication with the filtering bed and an air-actuated transfer system for loading and discharging this bed through these compartments. Facilities of this kind are used mainly in the nuclear and chemical engineering industries to rid their waste of radio-iodines, generally constituted by elementary iodine and methyl iodide, or of toxic gases that contaminate them. The granulated material, whose job it is to trap these contaminants by adsorption or absorption, is generally composed of active carbon or zeolites whose utilisation time is limited [fr

  8. Organic-mineral binder for molybdenum concentrate granulation

    International Nuclear Information System (INIS)

    Guro, Vitaliy P.; Ibragimova, Matluba A.; Safarov, Edgorjon T.

    2016-01-01

    Process of pyrite cinders production from Mo middlings consists of molybdenite concentrate granulation, firing to oxidize sulfide minerals and to recover Re-oxide. If kaolin binder is used a pyrite cinders dilution with Mo takes place. So, the development of organic binding agents, alternative to kaolin, is an actual issue. The approach is based on the comparison of the hydrophilic, strength and technological features of the hydrometallurgical processing of pellets. The new batch is developed. It differs from the traditional mixture by polymer burning and minimizing Mo dilution, thus aiming to maximize Re, Au, Ag recovery. The composition of the new organic-mineral batch is as follows: 97.3 % of molybdenite concentrate, 2 % of kaolin and 0.7 % of SK polymer. Keywords: molybdenum middlings, binder, organic additive, batch, granulation.

  9. Multivariate modelling of the tablet manufacturing process with wet granulation for tablet optimization and in-process control

    NARCIS (Netherlands)

    Westerhuis, J.A; Coenegracht, P.M J; Lerk, C.F

    1997-01-01

    The process of tablet manufacturing with granulation is described as a two-step process. The first step comprises wet granulation of the powder mixture, and in the second step the granules are compressed into tablets. For the modelling of the pharmaceutical process of wet granulation and tableting,

  10. Spontaneous calcium waves in granule cells in cerebellar slice cultures

    DEFF Research Database (Denmark)

    Apuschkin, Mia; Ougaard, Maria; Rekling, Jens C

    2013-01-01

    Multiple regions in the CNS display propagating correlated activity during embryonic and postnatal development. This activity can be recorded as waves of increased calcium concentrations in spiking neurons or glia cells, and have been suggested to be involved in patterning, axonal guidance and es......, that the propagating wave activity is carried through the tissue by axonal collaterals formed by neighboring granule cells, and further suggest that the correlated activity may be related to processes that ensure correct postnatal wiring of the cerebellar circuits....

  11. Lewis M. Rutherfurd and the First Photograph of Solar Granulation

    Science.gov (United States)

    Harvey, J. W.; Briggs, John W.; Prosser, Sian

    2017-08-01

    A major astronomical controversy of the mid-19th century was discordant descriptions of the small scale structure of the solar surface. Visual observers contradicted each other by describing the surface as consisting of “corrugations”, “willow leaves”, “rice grains”, “cumuli”, “thatch”, “granules”, etc. Early photographs of the solar surface were not good enough to settle the controversy. The French astronomer Jules Janssen is credited with the first 1876 photographs that clearly showed what we now call solar granulation (1876, CRAS 82, 1363). Upon seeing these images, New Yorker Lewis M. Rutherfurd (1878, MNRAS 38, 410) praised the high quality of Janssen’s images but asserted that he had also photographed granulation as early as 1871 using collodion wet plates. He sent copies of his best photograph to the Royal Astronomical Society to support his assertion. Curious about his claim, Briggs and Harvey set up Rutherfurd’s 13-inch achromatic refractor on Kitt Peak and found that it easily showed well-resolved solar granulation, so his claim might well have been justified. But without his plates we could not confirm the claim. For 140 years the copies of Rutherfurd’s best solar photograph remained in the archives of the Royal Astronomical Society and were recently discovered by Prosser (RAS Photographs A3/001B and A3/002). By coincidence a few days later, Briggs found the original August 11, 1871 plate. Despite poor condition these photographs show solar granulation. There are at least two other possible early claimants (Reade; Vogel) but their plates are almost certainly lost. Rutherfurd was a master of astronomical instrumentation and photography. He was reticent about his work, letting results speak for themselves, so it is satisfying to find that he was justified in making his claim of priority.

  12. Studies on the influence of laser beams on wound granulation

    International Nuclear Information System (INIS)

    Brunner, R.

    1982-01-01

    The influence of laser light of law energy on wound healing was tested on 204 rats in a blind study. The growth of granulation tissue in a polyvinylchloride cylinder implanted on the backs of the animals served as parameter for wound healing. Irradiation was carried out with a helium-neon laser (wavelength 632.8 nm) at daily doses of 0.5 J/cm 2 , 1.5 J/cm 2 , 4 J/cm 2 , 10 J/cm 2 and 20 J/cm 2 , and with incoherent non-linear polarized red light (wavelength 630 nm) with a daily dose of 4 J/cm 2 . This was repeated 8 times. Laser irradiation caused a statistically significant increase in wet and dry granulation tissue weight of 25% in the dose range 1.5 J/cm 2 to 20 J/cm 2 . At 0.5 J/cm 2 the effect was less, but the least effect was achieved by non-linear polarized incoherent red light. Bacteriological evaluation of wound germ counts revealed a marginally lower presence of high germ cell densities. In irradiated animals, histological and enzyme cytochemical findings revealed, in addition to a significant findings revealed, in addition to a significant increase in mast cells, a smaller increase in fibroblast count and a slight decrease in granulocytic and histiocytic elements. The biochemical evaluation of granulation tissue revealed no differences in collagen content between irradiated and unirradiated animals. (orig.) [de

  13. Convergent evolution of germ granule nucleators: A hypothesis.

    Science.gov (United States)

    Kulkarni, Arpita; Extavour, Cassandra G

    2017-10-01

    Germ cells have been considered "the ultimate stem cell" because they alone, during normal development of sexually reproducing organisms, are able to give rise to all organismal cell types. Morphological descriptions of a specialized cytoplasm termed 'germ plasm' and associated electron dense ribonucleoprotein (RNP) structures called 'germ granules' within germ cells date back as early as the 1800s. Both germ plasm and germ granules are implicated in germ line specification across metazoans. However, at a molecular level, little is currently understood about the molecular mechanisms that assemble these entities in germ cells. The discovery that in some animals, the gene products of a small number of lineage-specific genes initiate the assembly (also termed nucleation) of germ granules and/or germ plasm is the first step towards facilitating a better understanding of these complex biological processes. Here, we draw on research spanning over 100years that supports the hypothesis that these nucleator genes may have evolved convergently, allowing them to perform analogous roles across animal lineages. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  14. First results on quiet and magnetic granulation from SOUP

    Science.gov (United States)

    Title, A. M.; Tarbell, T. D.; Acton, L.; Duncan, D.; Ferguson, S. H.; Finch, M.; Frank, Z.; Kelly, G.; Lindgren, R.; Morrill, M.

    1987-01-01

    The flight of Solar Optical Universal Polarimeter (SOUP) on Spacelab 2 allowed the collection of time sequences of diffraction limited (0.5 arc sec) granulation images with excellent pointing (0.003 arc sec) and completely free of the distortion that plagues groundbased images. The p-mode oscillations are clearly seen in the data. Using Fourier transforms in the temporal and spatial domain, it was shown that the p-modes dominate the autocorrelation lifetime in magnetic regions. When these oscillations are removed the autocorrelation lifetime is found to be 500 sec in quiet and 950 sec in magnetic regions. In quiet areas exploding granules are seen to be common. It is speculated that a significant fraction of granule lifetimes are terminated by nearby explosions. Using local correlation tracking techniques it was able to measure horizontal displacements, and thus transverse velocities, in the magnetic field. In quiet sun it is possible to detect both super and mesogranulation. Horizontal velocities are as great as 1000 m/s and the average velocity is 400 m/s. In magnetic regions horizontal velocities are much less, about 100 m/s.

  15. Recreating the synthesis of starch granules in yeast

    Science.gov (United States)

    Pfister, Barbara; Sánchez-Ferrer, Antoni; Diaz, Ana; Lu, Kuanjen; Otto, Caroline; Holler, Mirko; Shaik, Farooque Razvi; Meier, Florence; Mezzenga, Raffaele; Zeeman, Samuel C

    2016-01-01

    Starch, as the major nutritional component of our staple crops and a feedstock for industry, is a vital plant product. It is composed of glucose polymers that form massive semi-crystalline granules. Its precise structure and composition determine its functionality and thus applications; however, there is no versatile model system allowing the relationships between the biosynthetic apparatus, glucan structure and properties to be explored. Here, we expressed the core Arabidopsis starch-biosynthesis pathway in Saccharomyces cerevisiae purged of its endogenous glycogen-metabolic enzymes. Systematic variation of the set of biosynthetic enzymes illustrated how each affects glucan structure and solubility. Expression of the complete set resulted in dense, insoluble granules with a starch-like semi-crystalline organization, demonstrating that this system indeed simulates starch biosynthesis. Thus, the yeast system has the potential to accelerate starch research and help create a holistic understanding of starch granule biosynthesis, providing a basis for the targeted biotechnological improvement of crops. DOI: http://dx.doi.org/10.7554/eLife.15552.001 PMID:27871361

  16. [Multi-mathematical modelings for compatibility optimization of Jiangzhi granules].

    Science.gov (United States)

    Yang, Ming; Zhang, Li; Ge, Yingli; Lu, Yanliu; Ji, Guang

    2011-12-01

    To investigate into the method of "multi activity index evaluation and combination optimized of mult-component" for Chinese herbal formulas. According to the scheme of uniform experimental design, efficacy experiment, multi index evaluation, least absolute shrinkage, selection operator (LASSO) modeling, evolutionary optimization algorithm, validation experiment, we optimized the combination of Jiangzhi granules based on the activity indexes of blood serum ALT, ALT, AST, TG, TC, HDL, LDL and TG level of liver tissues, ratio of liver tissue to body. Analytic hierarchy process (AHP) combining with criteria importance through intercriteria correlation (CRITIC) for multi activity index evaluation was more reasonable and objective, it reflected the information of activity index's order and objective sample data. LASSO algorithm modeling could accurately reflect the relationship between different combination of Jiangzhi granule and the activity comprehensive indexes. The optimized combination of Jiangzhi granule showed better values of the activity comprehensive indexed than the original formula after the validation experiment. AHP combining with CRITIC can be used for multi activity index evaluation and LASSO algorithm, it is suitable for combination optimized of Chinese herbal formulas.

  17. First results on quiet and magnetic granulation from SOUP

    Science.gov (United States)

    Title, A. M.; Tarbell, T. D.; Acton, L.; Duncan, D.; Ferguson, S. H.; Finch, M.; Frank, Z.; Kelly, G.; Lindgren, R.; Morrill, M.

    1987-09-01

    The flight of Solar Optical Universal Polarimeter (SOUP) on Spacelab 2 allowed the collection of time sequences of diffraction limited (0.5 arc sec) granulation images with excellent pointing (0.003 arc sec) and completely free of the distortion that plagues groundbased images. The p-mode oscillations are clearly seen in the data. Using Fourier transforms in the temporal and spatial domain, it was shown that the p-modes dominate the autocorrelation lifetime in magnetic regions. When these oscillations are removed the autocorrelation lifetime is found to be 500 sec in quiet and 950 sec in magnetic regions. In quiet areas exploding granules are seen to be common. It is speculated that a significant fraction of granule lifetimes are terminated by nearby explosions. Using local correlation tracking techniques it was able to measure horizontal displacements, and thus transverse velocities, in the magnetic field. In quiet sun it is possible to detect both super and mesogranulation. Horizontal velocities are as great as 1000 m/s and the average velocity is 400 m/s. In magnetic regions horizontal velocities are much less, about 100 m/s.

  18. The exocrine pancreas: the acinar-ductal tango in physiology and pathophysiology.

    Science.gov (United States)

    Hegyi, Peter; Petersen, Ole H

    2013-01-01

    There are many reviews of pancreatic acinar cell function and also of pancreatic duct function, but there is an almost total absence of synthetic reviews bringing the integrated functions of these two vitally and mutually interdependent cells together. This is what we have attempted to do in this chapter. In the first part, we review the normal integrated function of the acinar-ductal system, with particular emphasis on how regulation of one type of cell also influences the other cell type. In the second part, we review a range of pathological processes, particularly those involved in acute pancreatitis (AP), an often-fatal human disease in which the pancreas digests itself, in order to explore how malfunction of one of the cell types adversely affects the function of the other.

  19. A comparative study of the influence of alpha-lactose monohydrate particle morphology on granule and tablet properties after roll compaction/dry granulation.

    Science.gov (United States)

    Grote, Simon; Kleinebudde, Peter

    2018-05-29

    The influence of particle morphology and size of alpha-lactose monohydrate on dry granules and tablets was studied. Four different morphologies were investigated: Two grades of primary crystals, which differed in their particle size and structure (compact crystals vs. agglomerates). The materials were roll compacted at different specific compaction forces and changes in the particle size distribution and the specific surface area were measured. Afterwards, two fractions of granules were pressed to tablets and the tensile strength was compared to that from tablets compressed from the raw materials. The specific surface area was increased induced by roll compaction/dry granulation for all materials. At increased specific compaction forces, the materials showed sufficient size enlargement. The morphology of lactose determined the strength of direct compressed tablets. In contrast, the strength of granule tablets was leveled by the previous compression step during roll compaction/dry granulation. Thus, the tensile strength of tablets compressed directly from the powder mixtures determined whether materials exhibited a loss in tabletability after roll compaction/dry granulation or not. The granule size had only a slight influence on the strength of produced tablets. In some cases, the fraction of smaller granules showed a higher tensile strength compared to the larger fraction.

  20. Tar DNA binding protein-43 (TDP-43 associates with stress granules: analysis of cultured cells and pathological brain tissue.

    Directory of Open Access Journals (Sweden)

    Liqun Liu-Yesucevitz

    2010-10-01

    Full Text Available Tar DNA Binding Protein-43 (TDP-43 is a principle component of inclusions in many cases of frontotemporal lobar degeneration (FTLD-U and amyotrophic lateral sclerosis (ALS. TDP-43 resides predominantly in the nucleus, but in affected areas of ALS and FTLD-U central nervous system, TDP-43 is aberrantly processed and forms cytoplasmic inclusions. The mechanisms governing TDP-43 inclusion formation are poorly understood. Increasing evidence indicates that TDP-43 regulates mRNA metabolism by interacting with mRNA binding proteins that are known to associate with RNA granules. Here we show that TDP-43 can be induced to form inclusions in cell culture and that most TDP-43 inclusions co-localize with SGs. SGs are cytoplasmic RNA granules that consist of mixed protein-RNA complexes. Under stressful conditions SGs are generated by the reversible aggregation of prion-like proteins, such as TIA-1, to regulate mRNA metabolism and protein translation. We also show that disease-linked mutations in TDP-43 increased TDP-43 inclusion formation in response to stressful stimuli. Biochemical studies demonstrated that the increased TDP-43 inclusion formation is associated with accumulation of TDP-43 detergent insoluble complexes. TDP-43 associates with SG by interacting with SG proteins, such as TIA-1, via direct protein-protein interactions, as well as RNA-dependent interactions. The signaling pathway that regulates SGs formation also modulates TDP-43 inclusion formation. We observed that inclusion formation mediated by WT or mutant TDP-43 can be suppressed by treatment with translational inhibitors that suppress or reverse SG formation. Finally, using Sudan black to quench endogenous autofluorescence, we also demonstrate that TDP-43 positive-inclusions in pathological CNS tissue co-localize with multiple protein markers of stress granules, including TIA-1 and eIF3. These data provide support for accumulating evidence that TDP-43 participates in the SG pathway.

  1. Undiagnosed pancreatic exocrine insufficiency and chronic pancreatitis in functional GI disorder patients with diarrhea or abdominal pain.

    Science.gov (United States)

    Talley, Nicholas J; Holtmann, Gerald; Nguyen, Quoc Nam; Gibson, Peter; Bampton, Peter; Veysey, Martin; Wong, James; Philcox, Stephen; Koloski, Natasha; Bunby, Lisa; Jones, Michael

    2017-11-01

    A previous UK study showed that 6.1% of patients with diarrhea-predominant irritable bowel syndrome (IBS-D) had evidence of severe pancreatic exocrine insufficiency (PEI), but these findings need replication. We aimed to identify the prevalence of PEI based on fecal elastase stool testing in consecutive outpatients presenting with chronic unexplained abdominal pain and/or diarrhea and/or IBS-D. Patients aged over 40 years presenting to hospital outpatient clinics from six sites within Australia with unexplained abdominal pain and/or diarrhea for at least 3 months and/or IBS-D were studied. Patients completed validated questionnaires and donated a stool sample in which elastase concentration was measured by ELISA. A concentration of abdominal CT. Two hundred eighteen patients (mean age of 60 years, 29.4% male) were studied. PEI was found in 4.6% (95% CI 2.2-8.3%) (n = 10), with five patients (2.3% (95% CI 0.8-5.3%) having severe PEI. Only male sex and heavy alcohol use were significantly associated with abnormal versus normal pancreatic functioning. Of seven patients who underwent endoscopic ultrasound or CT, two had features indicative of chronic pancreatitis. One in 50 patients with IBS-D or otherwise unexplained abdominal pain or diarrhea have an abnormal fecal elastase, but unexpected pancreatic insufficiency was detected in only a minority of these. This study failed to confirm the high prevalence of PEI among patients with unexplained GI symptoms previously reported. © 2017 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  2. The prevalence of small intestinal bacterial overgrowth in non-surgical patients with chronic pancreatitis and pancreatic exocrine insufficiency (PEI).

    Science.gov (United States)

    Ní Chonchubhair, Hazel M; Bashir, Yasir; Dobson, Mark; Ryan, Barbara M; Duggan, Sinead N; Conlon, Kevin C

    2018-02-24

    Small intestinal bacterial overgrowth (SIBO) is a condition characterised by symptoms similar to pancreatic exocrine insufficiency (PEI) in chronic pancreatitis patients. SIBO is thought to complicate chronic pancreatitis in up to 92% of cases; however, studies are heterogeneous and protocols non-standardised. SIBO may be determined by measuring lung air-expiration of either hydrogen or methane which are by-products of small bowel bacterial fermentation of intraluminal substrates such as carbohydrates. We evaluated the prevalence of SIBO among a defined cohort of non-surgical chronic pancreatitics with mild to severe PEI compared with matched healthy controls. Thirty-five patients and 31 age-, gender- and smoking status-matched healthy controls were evaluated for SIBO by means of a fasting glucose hydrogen breath test (GHBT). The relationship between SIBO and clinical symptoms in chronic pancreatitis was evaluated. SIBO was present in 15% of chronic pancreatitis patients, while no healthy controls tested positive (P = 0.029). SIBO was more prevalent in those taking pancreatic enzyme replacement therapy (PERT) (P = 0.016), with proton pump inhibitor use (PPI) (P = 0.022) and in those with alcohol aetiology (P = 0.023). Patients with concurrent diabetes were more often SIBO-positive and this was statistically significant (P = 0.009). There were no statistically significant differences in reported symptoms between patients with and without SIBO, with the exception of 'weight loss', with patients reporting weight loss more likely to have SIBO (P = 0.047). The prevalence of SIBO in this study was almost 15% and consistent with other studies of SIBO in non-surgical chronic pancreatitis patients. These data support the testing of patients with clinically-relevant PEI unresolved by adequate doses of PERT, particularly in those patients with concurrent diabetes. SIBO can be easily diagnosed therefore allowing more specific and more targeted symptom

  3. Prececal digestibility of various sources of starch in minipigs with or without experimentally induced exocrine pancreatic insufficiency.

    Science.gov (United States)

    Mösseler, A; Kramer, N; Becker, C; Gregory, P C; Kamphues, J

    2012-12-01

    Low prececal digestibility of starch leads to a higher starch flux into the hindgut, causing a forced microbial fermentation, energy losses, and meteorism. For exocrine pancreatic insufficiency (EPI), lack of pancreatic amylase can be compensated mostly by hindgut fermentation of starch. Even in pigs with complete loss of pancreatic secretion, starch digestibility over the entire tract is reaching levels of controls. To optimize diets for human patients with EPI, the proportion of starch that is digested by the ileum is important. Minipigs were fitted with an ileocecal reentrant fistula (n = 8) to determine prececal digestibility of starch. In 5 minipigs the pancreatic duct was ligated (PL) to induce EPI; 3 minipigs served as controls (Con). Various starch sources were tested in a 1-d screening test; therefore, disappearance rate (DR) instead of digestibility was used. Test meals consisted of 169 g DM of a basal diet plus 67.5 g DM of the starch (without thermal treatment; purified; starch content of 89 to 94.5%) and Cr(2)O(3). The test meal contained (% of DM) starch, 67; crude fat, 1.69; CP, 15; crude fiber, 2.0; and Cr(2)O(3), 0.25. In PL, prececal DR of starch was lower than in Con (P 90%) but was lower (P < 0.05) for potato (Solanum tuberosum) starch (75.4%). In PL, prececal DR of starch was higher (P < 0.05) for wheat (Triticum aestivum) starch (61.2%) than corn (Zea mays) starch (43.0%) and rice (Oryza sativa) starch (29.2%) and intermediate for potato and field pea (Pisum sativum) starch. For patients with EPI, wheat starch seems favorable due to the higher prececal digestibility whereas raw corn and rice starch should be avoided.

  4. Melting of fuel element racks and their recycling as granulate

    International Nuclear Information System (INIS)

    Quade, U.; Kluth, T.; Kreh, R.

    1998-01-01

    In order to increase the storage capacity for spent fuel elements in the Spanish NPPs of Almaraz and Asco, the existing racks were replaced by compact one in 1991/1993. The 28 racks from Almaraz NPP were cut on site, packed in 200-I-drums and taken to intermediate storage. For the remaining 28 racks of Asco NPP, ENRESA preferred the melting alternative. To demonstrate the recycling path melting in Germany, a test campaign with six racks was performed in 1997. As a result of this test melt, the limits for Carla melting plant were modified to 200 Bq/g total, α, β, γ 100 Bq/g nuclear fuels, max. 3g/100 kg 2,000 Bq/g total Fe55, H 3 , C-14 and Ni63. After the test melt campaign, the German authorities licensed the import and treatment of the remaining 22 racks on the condition that the waste resulting from the melting process as well as the granules produced were taken back to Spain. The shipment from Asco via France to Germany has been carried out in F 20-ft-IPII containers in accordance with ADR. Size reduction to chargeable dimensions was carried out by a plasma burner and hydraulic shears. For melting, a 3.2 Mg medium frequency induction furnace, operated in a separate housing, was used. For granules production outside this housing, the liquid iron was cast into a 5Mg ladle and then, through a water jet, into the granulating basin. The total mass of 287,659 Kg of 28 fuel elements racks and components of the storage basin yielded 297,914 kg of iron granulate. Secondary waste from melting amounted to 9,920 kg, corresponding to 3.45% of the input mass. The granulating process produced 6,589 kg, corresponding to 2.28% of the total mass to be melted. Radiological analysis of samples taken from the melt and different waste components confirmed the main nuclides Co60, Cs134 and Cs137. Fe55 was highly overestimated by the preliminary analysis. (Author) 2 refs

  5. Formation of tRNA granules in the nucleus of heat-induced human cells

    International Nuclear Information System (INIS)

    Miyagawa, Ryu; Mizuno, Rie; Watanabe, Kazunori; Ijiri, Kenichi

    2012-01-01

    Highlights: ► tRNAs are tranlocated into the nucleus in heat-induced HeLa cells. ► tRNAs form the unique granules in the nucleus. ► tRNA ganules overlap with nuclear stress granules. -- Abstract: The stress response, which can trigger various physiological phenomena, is important for living organisms. For instance, a number of stress-induced granules such as P-body and stress granule have been identified. These granules are formed in the cytoplasm under stress conditions and are associated with translational inhibition and mRNA decay. In the nucleus, there is a focus named nuclear stress body (nSB) that distinguishes these structures from cytoplasmic stress granules. Many splicing factors and long non-coding RNA species localize in nSBs as a result of stress. Indeed, tRNAs respond to several kinds of stress such as heat, oxidation or starvation. Although nuclear accumulation of tRNAs occurs in starved Saccharomyces cerevisiae, this phenomenon is not found in mammalian cells. We observed that initiator tRNA Met (Meti) is actively translocated into the nucleus of human cells under heat stress. During this study, we identified unique granules of Meti that overlapped with nSBs. Similarly, elongator tRNA Met was translocated into the nucleus and formed granules during heat stress. Formation of tRNA granules is closely related to the translocation ratio. Then, all tRNAs may form the specific granules.

  6. Impact of functionalized particle structure on roll compaction/dry granulation and tableting of calcium carbonate.

    Science.gov (United States)

    Grote, Simon; Kleinebudde, Peter

    2018-06-10

    The influence of a functionalized raw material particle structure on the granulation behavior and tabletabilty of calcium carbonate (CaCO 3 ) was investigated. Therefore, a milled grade of CaCO 3 was compared to different binary mixtures of milled and functionalized CaCO 3 . Relevant properties of raw materials, ribbons and granules were measured. The starting materials and two fractions of dry granules were compressed to tablets. The tabletability of granules was compared to that of the powders and the influence of specific compaction force and granule size on tablet tensile strength was evaluated. Adding functionalized particles drastically influenced the granulation and tableting behavior of CaCO 3 . Increasing proportions increased the ribbon porosity and granule size. Tensile strength of tablets from powder mixtures and granules was increased as well. Nevertheless, adding functionalized CaCO 3 led to a loss in tabletability induced by a previous compaction step to an extent depending on its proportion in the formulation. A clear influence of the particle morphology on granulation and tableting behavior was demonstrated by the study. The functionalized structure showed aspects of a more plastic deformation behavior. Adding functionalized CaCO 3 to a mixture, even in small amounts, seemed to be beneficial to increase granule size and tablet strength. Copyright © 2018 Elsevier B.V. All rights reserved.

  7. Control over the morphology and segregation of Zebrafish germ cell granules during embryonic development

    Directory of Open Access Journals (Sweden)

    Nakkrasae La-Iad

    2008-05-01

    Full Text Available Abstract Background Zebrafish germ cells contain granular-like structures, organized around the cell nucleus. These structures share common features with polar granules in Drosophila, germinal granules in Xenopus and chromatoid bodies in mice germ cells, such as the localization of the zebrafish Vasa, Piwi and Nanos proteins, among others. Little is known about the structure of these granules as well as their segregation in mitosis during early germ-cell development. Results Using transgenic fish expressing a fluorescently labeled novel component of Zebrafish germ cell granules termed Granulito, we followed the morphology and distribution of the granules. We show that whereas these granules initially exhibit a wide size variation, by the end of the first day of development they become a homogeneous population of medium size granules. We investigated this resizing event and demonstrated the role of microtubules and the minus-end microtubule dependent motor protein Dynein in the process. Last, we show that the function of the germ cell granule resident protein the Tudor domain containing protein-7 (Tdrd7 is required for determination of granule morphology and number. Conclusion Our results suggest that Zebrafish germ cell granules undergo a transformation process, which involves germ cell specific proteins as well as the microtubular network.

  8. The transformation from anammox granules to deammonification granules in micro-aerobic system by facilitating indigenous ammonia oxidizing bacteria.

    Science.gov (United States)

    Wang, Xiaolong; Gao, Dawen

    2018-02-01

    Granular deammonification process is a good way to retain aerobic and anaerobic ammonia oxidizing bacteria (AOB and anammox bacteria) and exhaust flocculent nitrite oxidizing bacteria (NOB). In this study, to facilitate indigenous AOB growth on anammox granules, by stepwise reducing influent nitrite, anammox granules were effectively transformed into deammonification granules in a micro-aerobic EGSB in 100 days. Total nitrogen removal efficiency of 90% and nitrogen removal rate of 2.3 g N/L/d were reached at stable deammonification stage. High influent FA and limited oxygen supply contributed suppression for Nitrospira-like NOB. In transition stages, Proteobacteria and Chloroflexi were always dominated. Anammox abundance decreased, while AOB abundance grew fast. Anammox bacteria and AOB were dominated by Brocadia fulgida and Nitrosomonas europaea, respectively. Denitrification activity and bacteria existed although without influent organic. The final AOB abundance was about 4.55-13.8 times more than anammox bacteria abundance, with almost equal potential activities. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Downstream processing from melt granulation towards tablets: In-depth analysis of a continuous twin-screw melt granulation process using polymeric binders.

    Science.gov (United States)

    Grymonpré, W; Verstraete, G; Vanhoorne, V; Remon, J P; De Beer, T; Vervaet, C

    2018-03-01

    The concept of twin-screw melt granulation (TSMG) has steadily (re)-gained interest in pharmaceutical formulation development as an intermediate step during tablet manufacturing. However, to be considered as a viable processing option for solid oral dosage forms there is a need to understand all critical sources of variability which could affect this granulation technique. The purpose of this study was to provide an in-depth analysis of the continuous TSMG process in order to expose the critical process parameters (CPP) and elucidate the impact of process and formulation parameters on the critical quality attributes (CQA) of granules and tablets during continuous TSMG. A first part of the study dealt with the screening of various amorphous polymers as binder for producing high-dosed melt granules of two model drug (i.e. acetaminophen and hydrochlorothiazide). The second part of this study described a quality-by-design (QbD) approach for melt granulation of hydrochlorothiazide in order to thoroughly evaluate TSMG, milling and tableting stage of the continuous TSMG line. Using amorphous polymeric binders resulted in melt granules with high milling efficiency due to their brittle behaviour without producing excessive amounts of fines, providing high granule yields with low friability. Therefore, it makes them extremely suitable for further downstream processing. One of the most important CPP during TSMG with polymeric binders was the granulation-torque, which - in case of polymers with high T g - increased during longer granulation runs to critical levels endangering the continuous process flow. However, by optimizing both screw speed and throughput or changing to polymeric binders with lower T g it was possible to significantly reduce this risk. This research paper highlighted that TSMG must be considered as a viable option during formulation development of solid oral dosage forms based on the robustness of the CQA of both melt granules and tablets. Copyright © 2017

  10. Host cell subversion by Toxoplasma GRA16, an exported dense granule protein that targets the host cell nucleus and alters gene expression.

    Science.gov (United States)

    Bougdour, Alexandre; Durandau, Eric; Brenier-Pinchart, Marie-Pierre; Ortet, Philippe; Barakat, Mohamed; Kieffer, Sylvie; Curt-Varesano, Aurélie; Curt-Bertini, Rose-Laurence; Bastien, Olivier; Coute, Yohann; Pelloux, Hervé; Hakimi, Mohamed-Ali

    2013-04-17

    After invading host cells, Toxoplasma gondii multiplies within a parasitophorous vacuole (PV) that is maintained by parasite proteins secreted from organelles called dense granules. Most dense granule proteins remain within the PV, and few are known to access the host cell cytosol. We identify GRA16 as a dense granule protein that is exported through the PV membrane and reaches the host cell nucleus, where it positively modulates genes involved in cell-cycle progression and the p53 tumor suppressor pathway. GRA16 binds two host enzymes, the deubiquitinase HAUSP and PP2A phosphatase, which exert several functions, including regulation of p53 and the cell cycle. GRA16 alters p53 levels in a HAUSP-dependent manner and induces nuclear translocation of the PP2A holoenzyme. Additionally, certain GRA16-deficient strains exhibit attenuated virulence, indicating the importance of these host alterations in pathogenesis. Therefore, GRA16 represents a potentially emerging subfamily of exported dense granule proteins that modulate host function. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. QGQS Granule in SHR Serum Metabonomics Study Based on Tools of UPLC-Q-TOF and Renin-Angiotensin-Aldosterone System Form Protein Profilin-1

    Directory of Open Access Journals (Sweden)

    Ke Li

    2017-01-01

    Full Text Available QGQS granule is effective for the therapeutic of hypertension in clinic. The aim of this research is to observe the antihypertension effect of QGQS granule on SHR and explain the mechanism of its lowering blood pressure. 30 SHR were selected as model group, captopril group, and QGQS group, 10 WKYr were used as control group, and RBP were measured on tail artery consciously. And all the serum sample analysis was carried out on UPLC-TOF-MS system to determine endogenous metabolites and to find the metabonomics pathways. Meanwhile, ELISA kits for the determination pharmacological indexes of PRA, AngI, AngII, and ALD were used for pathway confirmatory; WB for determination of profilin-1 protein expression was conducted for Ang II pathway analysis as well. It is demonstrated that QGQS granule has an excellent therapeutic effect on antihypertension, which exerts effect mainly on metabonomics pathway by regulating glycerophospholipid, sphingolipid, and arachidonic acid metabolism, and it could inhibit the overexpression of the profilin-1 protein. We can come to a conclusion that RAAS should be responsible mainly for the metabonomics pathway of QGQS granule on antihypertension, and it plays a very important role in protein of profilin-1 inhibition.

  12. Influence of raw material properties upon critical quality attributes of continuously produced granules and tablets

    DEFF Research Database (Denmark)

    Fonteyne, Margot; Wickström, Henrika; Peeters, Elisabeth

    2014-01-01

    over a range of raw material attributes, manufacturing process options and process parameters. This fits further into the Process Analytical Technology (PAT) and Quality by Design (QbD) framework. The present study evaluates the effect of variation in critical raw material properties on the critical......-Lactose-PVP (30-67.5-2.5%) was used as model formulation. Seven different grades of theophylline were granulated. Afterward, the obtained granules were tableted. Both the characteristics of granules and tablets were determined. The results show that differences in raw material properties both affect...... quality attributes of granules and tablets, produced by a continuous from-powder-to-tablet wet granulation line. The granulation process parameters were kept constant to examine the differences in the end product quality caused by the variability of the raw materials properties only. Theophylline...

  13. The herpes simplex virus 2 virion-associated ribonuclease vhs interferes with stress granule formation.

    Science.gov (United States)

    Finnen, Renée L; Hay, Thomas J M; Dauber, Bianca; Smiley, James R; Banfield, Bruce W

    2014-11-01

    In a previous study, it was observed that cells infected with herpes simplex virus 2 (HSV-2) failed to accumulate stress granules (SGs) in response to oxidative stress induced by arsenite treatment. As a follow-up to this observation, we demonstrate here that disruption of arsenite-induced SG formation by HSV-2 is mediated by a virion component. Through studies on SG formation in cells infected with HSV-2 strains carrying defective forms of UL41, the gene that encodes vhs, we identify vhs as a virion component required for this disruption. Cells infected with HSV-2 strains producing defective forms of vhs form SGs spontaneously late in infection. In addition to core SG components, these spontaneous SGs contain the viral immediate early protein ICP27 as well as the viral serine/threonine kinase Us3. As part of these studies, we reexamined the frameshift mutation known to reside within the UL41 gene of HSV-2 strain HG52. We demonstrate that this mutation is unstable and can rapidly revert to restore wild-type UL41 following low-multiplicity passaging. Identification of the involvement of virion-associated vhs in the disruption of SG formation will enable mechanistic studies on how HSV-2 is able to counteract antiviral stress responses early in infection. In addition, the ability of Us3 to localize to stress granules may indicate novel roles for this viral kinase in the regulation of translation. Eukaryotic cells respond to stress by rapidly shutting down protein synthesis and storing mRNAs in cytoplasmic stress granules (SGs). Stoppages in protein synthesis are problematic for all viruses as they rely on host cell machinery to synthesize viral proteins. Thus, many viruses target SGs for disruption or modification. Infection by herpes simplex virus 2 (HSV-2) was previously observed to disrupt SG formation induced by oxidative stress. In this follow-up study, we identify virion host shutoff protein (vhs) as a viral protein involved in this disruption. The

  14. In vivo Anomalous Diffusion and Weak Ergodicity Breaking of Lipid Granules

    DEFF Research Database (Denmark)

    Jeon, J.-H.; Tejedor, V.; Burov, S.

    2011-01-01

    Combining extensive single particle tracking microscopy data of endogenous lipid granules in living fission yeast cells with analytical results we show evidence for anomalous diffusion and weak ergodicity breaking. Namely we demonstrate that at short times the granules perform subdiffusion...... according to the laws of continuous time random walk theory. The associated violation of ergodicity leads to a characteristic turnover between two scaling regimes of the time averaged mean squared displacement. At longer times the granule motion is consistent with fractional Brownian motion....

  15. Proteome profiling of human neutrophil granule subsets, secretory vesicles, and cell membrane

    DEFF Research Database (Denmark)

    Rørvig, Sara; Østergaard, Ole; Heegaard, Niels Henrik Helweg

    2013-01-01

    granules, SVs, and plasma membrane has been performed before. Here, we performed subcellular fractionation on freshly isolated human neutrophils by nitrogen cavitation and density centrifugation on a four-layer Percoll gradient. Granule subsets were pooled and subjected to SDS-PAGE, and gel pieces were in...... subcellular proteome profiles presented here may be used as a database in combination with the mRNA array database to predict and test the presence and localization of proteins in neutrophil granules and membranes....

  16. High level waste containing granules coated and embedded in metal as an alternative to HLW glasses

    International Nuclear Information System (INIS)

    Neumann, W.

    1980-01-01

    Simulated high level waste containing granules were overcoated with pyrocarbon or nickel respectively. The coatings were performed by the use of chemical vapour deposition in a fluidized bed. The coated granules were embedded in an aluminium-silicon-alloy to improve the dissipation of radiation induced heat. The metal-granules-composites obtained were of improved product stability related to the high level waste containing glasses. (orig.) [de

  17. Role of the Caenorhabditis elegans multidrug resistance gene, mrp-4, in gut granule differentiation.

    Science.gov (United States)

    Currie, Erin; King, Brian; Lawrenson, Andrea L; Schroeder, Lena K; Kershner, Aaron M; Hermann, Greg J

    2007-11-01

    Caenorhabditis elegans gut granules are lysosome-related organelles with birefringent contents. mrp-4, which encodes an ATP-binding cassette (ABC) transporter homologous to mammalian multidrug resistance proteins, functions in the formation of gut granule birefringence. mrp-4(-) embryos show a delayed appearance of birefringent material in the gut granule but otherwise appear to form gut granules properly. mrp-4(+) activity is required for the extracellular mislocalization of birefringent material, body-length retraction, and NaCl sensitivity, phenotypes associated with defective gut granule biogenesis exhibited by embryos lacking the activity of GLO-1/Rab38, a putative GLO-1 guanine nucleotide exchange factor GLO-4, and the AP-3 complex. Multidrug resistance protein (MRP)-4 localizes to the gut granule membrane, consistent with it playing a direct role in the transport of molecules that compose and/or facilitate the formation of birefringent crystals within the gut granule. However, MRP-4 is also present in oocytes and early embryos, and our genetic analyses indicate that its site of action in the formation of birefringent material may not be limited to just the gut granule in embryos. In a search for genes that function similarly to mrp-4(+), we identified WHT-2, another ABC transporter that acts in parallel to MRP-4 for the formation of birefringent material in the gut granule.

  18. The Effect of Wetting on The Course of The Drum Granulation

    Directory of Open Access Journals (Sweden)

    Błaszczyk Michał

    2017-06-01

    Full Text Available This paper presents the results of experimental drum granulation of silica flour with the use of wetting liquids with different values of surface tension. Additionally, different liquid jet breakup and different residual moisture of the bed were applied in the tests. The process was conducted periodically in two stages: wetting and proper granulation, during which no liquid was supplied to the bed. The condition of the granulated material after the period of wetting (particle size distribution and moisture of separate fractions and a change in the particle size distribution during the further conduct of the process (granulation kinetics were determined.

  19. Three novel proteins co-localise with polyhydroxybutyrate (PHB) granules in Rhodospirillum rubrum S1.

    Science.gov (United States)

    Narancic, Tanja; Scollica, Elisa; Cagney, Gerard; O'Connor, Kevin E

    2018-04-01

    Polyhydroxybutyrate (PHB), a biodegradable polymer accumulated by bacteria is deposited intracellularly in the form of inclusion bodies often called granules. The granules are supramolecular complexes harbouring a varied number of proteins on their surface, which have specific but incompletely characterised functions. By comparison with other organisms that produce biodegradable polymers, only two phasins have been described to date for Rhodosprillum rubrum, raising the possibility that more await discovery. Using a comparative proteomics strategy to compare the granules of wild-type R. rubrum with a PHB-negative mutant housing artificial PHB granules, we identified four potential PHB granules' associated proteins. These were: Q2RSI4, an uncharacterised protein; Q2RWU9, annotated as an extracellular solute-binding protein; Q2RQL4, annotated as basic membrane lipoprotein; and Q2RQ51, annotated as glucose-6-phosphate isomerase. In silico analysis revealed that Q2RSI4 harbours a Phasin_2 family domain and shares low identity with a single-strand DNA-binding protein from Sphaerochaeta coccoides. Fluorescence microscopy found that three proteins Q2RSI4, Q2EWU9 and Q2RQL4 co-localised with PHB granules. This work adds three potential new granule associated proteins to the repertoire of factors involved in bacterial storage granule formation, and confirms that proteomics screens are an effective strategy for discovery of novel granule associated proteins.

  20. Layered growth with bottom-spray granulation for spray deposition of drug.

    Science.gov (United States)

    Er, Dawn Z L; Liew, Celine V; Heng, Paul W S

    2009-07-30

    The gap in scientific knowledge on bottom-spray fluidized bed granulation has emphasized the need for more studies in this area. This paper comparatively studied the applicability of a modified bottom-spray process and the conventional top-spray process for the spray deposition of a micronized drug during granulation. The differences in circulation pattern, mode of growth and resultant granule properties between the two processes were highlighted. The more ordered and consistent circulation pattern of particles in a bottom-spray fluidized bed was observed to give rise to layered granule growth. This resulted in better drug content uniformity among the granule batches and within a granule batch. The processes' sensitivities to wetting and feed material characteristics were also compared and found to differ markedly. Less robustness to differing process conditions was observed for the top-spray process. The resultant bottom-spray granules formed were observed to be less porous, more spherical and had good flow properties. The bottom-spray technique can thus be potentially applied for the spray deposition of drug during granulation and was observed to be a good alternative to the conventional technique for preparing granules.

  1. Comparison of Ca2+ and Mg2+ enhancing aerobic granulation in SBR

    International Nuclear Information System (INIS)

    Liu Lin; Gao Dawen; Zhang Min; Fu Yuan

    2010-01-01

    Two sequencing batch reactors (SBRs) were operated to investigate the effect of Ca 2+ and Mg 2+ augmentation on aerobic granulation. Reactor R1 was augmented with Ca 2+ at 40 mg/L, while Mg 2+ was added to the reactor R2 with 40 mg/L. Results showed that the reactor R1 had a faster granulation process compared with R2, and the mature granules in R1 showed better physical characteristics. However, the mature granules in R2 had the higher production yield of polysaccharides and proteins, and aerobic granules in R2 experienced a faster substrate biodegradation. Microbial and genetic characteristics in mature granules were analyzed using polymerase chain reaction (PCR) and denaturing gradient gel electrophoresis (DGGE) techniques. The results revealed that Mg 2+ addition led to higher microbial diversity in mature granules. In addition, an uncultured bacterium (AB447697) was major specie in R1, and β-proteobacterium was dominant in R2. It can be concluded that Ca 2+ had an important effect on physical properties of aerobic granules, while Mg 2+ played a key role on biological properties during the sludge granulation.

  2. Titanium Granules for Augmentation of the Maxillary Sinus

    DEFF Research Database (Denmark)

    Lyngstadaas, Ståle Petter; Verket, Anders; Pinholt, Else Marie

    2015-01-01

    BACKGROUND: Biomaterials are commonly used to augment the maxillary sinus floor prior to or in conjunction with dental implant installation. Recently, porous titanium granules (PTGs) have been used in oral implant surgery to stabilize implants and function as an osteoconductive matrix. PURPOSE...... in the study. RESULTS: One immobile implant was removed. The mean marginal bone loss was 0.5 mm and 0.8 mm, on the mesial and distal side, respectively. Histologically, all biopsies demonstrated bone ingrowth. CONCLUSIONS: The results suggest that PTG can be safely and effectively used as augmentation material...

  3. Identification of the Polyhydroxybutyrate Granules in Mammalian Cultured Cells

    OpenAIRE

    Elustondo, Pia; Zakharian, Eleonora; Pavlov, Evgeny

    2012-01-01

    Poly-3-hydroxybutyrate (PHB) is a biological polyester present in bacteria and eukaryotic cells. Long-chain (or storage) sPHB (up to 100,000 residues) is typically present in PHB-accumulating bacteria and localized in specialized granules known as carbonosomes. In these organisms, sPHB plays a major role as carbon and energy storage. On the other hand, short-chain (or complexed) cPHB (10–100 residues) is present in eukaryotic organisms, including mammals as well as in many bacteria. Previous ...

  4. New gentle-wing high-shear granulator: impact of processing variables on granules and tablets characteristics of high-drug loading formulation using design of experiment approach.

    Science.gov (United States)

    Fayed, Mohamed H; Abdel-Rahman, Sayed I; Alanazi, Fars K; Ahmed, Mahrous O; Tawfeek, Hesham M; Al-Shdefat, Ramadan I

    2017-10-01

    The aim of this work was to study the application of design of experiment (DoE) approach in defining design space for granulation and tableting processes using a novel gentle-wing high-shear granulator. According to quality-by-design (QbD) prospective, critical attributes of granules, and tablets should be ensured by manufacturing process design. A face-centered central composite design has been employed in order to investigate the effect of water amount (X 1 ), impeller speed (X 2 ), wet massing time (X 3 ), and water addition rate (X 4 ) as independent process variables on granules and tablets characteristics. Acetaminophen was used as a model drug and granulation experiments were carried out using dry addition of povidone k30. The dried granules have been analyzed for their size distribution, density, and flow pattern. Additionally, the produced tablets have been investigated for; weight uniformity, breaking force, friability and percent capping, disintegration time, and drug dissolution. Results of regression analysis showed that water amount, impeller speed and wet massing time have significant (p tablets characteristics. However, the water amount had the most pronounced effect as indicated by its higher parameter estimate. On the other hand, water addition rate showed a minimal impact on granules and tablets properties. In conclusion, water amount, impeller speed, and wet massing time could be considered as critical process variables. Thus, understanding the relationship between these variables and quality attributes of granules and corresponding tablets provides the basis for adjusting granulation variables in order to optimize product performance.

  5. Prevalence of exocrine pancreatic insufficiency in patients with chronic pancreatitis without follow-up. PANCR-EVOL Study.

    Science.gov (United States)

    Marra-Lopez Valenciano, Carlos; Bolado Concejo, Federico; Marín Serrano, Eva; Millastre Bocos, Judith; Martínez-Moneo, Emma; Pérez Rodríguez, Esperanza; Francisco González, María; Del Pozo-García, Andrés; Hernández Martín, Anaiansi; Labrador Barba, Elena; Orera Peña, María Luisa; de-Madaria, Enrique

    2018-02-01

    Exocrine pancreatic insufficiency (EPI) is an important complication of chronic pancreatitis (CP). Guidelines recommend to rule out EPI in CP, to detect those patients who would benefit from pancreatic enzyme replacement therapy. The aim of this study was to evaluate the prevalence of EPI in patients with CP without follow-up in the last 2 years and to describe their nutritional status and quality of life (QoL). This was a cross-sectional, multicenter Spanish study. CP patients without follow-up by a gastroenterologist or surgeon in at least 2 years were included. EPI was defined as fecal elastase test <200mcg/g. For nutritional assessment, laboratory and anthropometric data were obtained. QoL was investigated using the EORTC QLQ-C30 questionnaire. 64 patients (mean age 58.8±10.3 years, 85.9% men) from 10 centers were included. Median time since diagnosis of CP was 58.7 months [37.7-95.4]. Forty-one patients (64.1%) had EPI. Regarding nutritional status, the following differences were observed (EPI vs. Non-EPI): BMI (23.9±3.5kg/m 2 vs. 25.7±2.5, p=0.03); glucose (121 [96-189] mg/dL vs. 98 [90-116], p=0.006); HbA1c 6.6% [6.0-8.4] vs. 5.5 [5.3-6.0], p=0.0005); Vitamin A (0.44mg/L [0.35-0.57] vs. 0.53 [0.47-0.63], p=0.048) and Vitamin E (11.2±5.0μg/ml vs. 14.4±4.3, p=0.03). EPI group showed a worse EORTC QLQ-C30 score on physical (93.3 [66.7-100] vs. 100 [93.3-100], p=0.048) and cognitive function (100 [83.3-100] vs. 100 [100-100], p=0.04). Prevalence of EPI is high in patients with CP without follow-up. EPI group had higher levels of glucose, lower levels of vitamins A and E and worse QoL. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  6. Efficacy and Safety of a New Formulation of Pancrelipase (Ultrase MT20 in the Treatment of Malabsorption in Exocrine Pancreatic Insufficiency in Cystic Fibrosis

    Directory of Open Access Journals (Sweden)

    Michael W. Konstan

    2010-01-01

    Full Text Available Background. Pancreatic enzyme replacement therapy is the standard of care for treatment of malabsorption in patients with cystic fibrosis (CF and exocrine pancreatic insufficiency (PI. Aim. To evaluate efficacy and safety of a new formulation of pancrelipase (Ultrase MT20 in patients with CF and PI. Coefficients of fat absorption (CFA% and nitrogen absorption (CNA% were the main efficacy parameters. Safety was evaluated by monitoring laboratory analyses, adverse events (AEs, and overall signs and symptoms. Methods. Patients (n=31 were randomized in a crossover design comparing this pancrelipase with placebo during 2 inpatient evaluation periods (6-7 days each. Fat and protein/nitrogen ingestion and excretion were measured from food diaries and 72-hour stool collections. CFA% and CNA% were calculated for each period and compared. Results. Twenty-four patients provided analyzable data. This pancrelipase increased mean CFA% and CNA% (+34.7% and +25.7%, resp., P<.0001 for both, reduced stool frequency, and improved stool consistency compared with placebo. Placebo-treated patients reported more AEs, with gastrointestinal symptoms being the most frequently reported AE. Conclusions. This pancrelipase is a safe and effective treatment for malabsorption associated with exocrine PI in patients with CF.

  7. Wolfram syndrome 1 gene (WFS1) product localizes to secretory granules and determines granule acidification in pancreatic beta-cells.

    Science.gov (United States)

    Hatanaka, Masayuki; Tanabe, Katsuya; Yanai, Akie; Ohta, Yasuharu; Kondo, Manabu; Akiyama, Masaru; Shinoda, Koh; Oka, Yoshitomo; Tanizawa, Yukio

    2011-04-01

    Wolfram syndrome is an autosomal recessive disorder characterized by juvenile-onset insulin-dependent diabetes mellitus and optic atrophy. The gene responsible for the syndrome (WFS1) encodes an endoplasmic reticulum (ER) resident transmembrane protein. The Wfs1-null mouse exhibits progressive insulin deficiency causing diabetes. Previous work suggested that the function of the WFS1 protein is connected to unfolded protein response and to intracellular Ca(2+) homeostasis. However, its precise molecular function in pancreatic β-cells remains elusive. In our present study, immunofluorescent and electron-microscopic analyses revealed that WFS1 localizes not only to ER but also to secretory granules in pancreatic β-cells. Intragranular acidification was assessed by measuring intracellular fluorescence intensity raised by the acidotrophic agent, 3-[2,4-dinitroanilino]-3'-amino-N-methyldipropyramine. Compared with wild-type β-cells, there was a 32% reduction in the intensity in WFS1-deficient β-cells, indicating the impairment of granular acidification. This phenotype may, at least partly, account for the evidence that Wfs1-null islets have impaired proinsulin processing, resulting in an increased circulating proinsulin level. Morphometric analysis using electron microscopy evidenced that the density of secretory granules attached to the plasma membrane was significantly reduced in Wfs1-null β-cells relative to that in wild-type β-cells. This may be relevant to the recent finding that granular acidification is required for the priming of secretory granules preceding exocytosis and may partly explain the fact that glucose-induced insulin secretion is profoundly impaired in young prediabetic Wfs1-null mice. These results thus provide new insights into the molecular mechanisms of β-cell dysfunction in patients with Wolfram syndrome.

  8. Tribology of swollen starch granule suspensions from maize and potato.

    Science.gov (United States)

    Zhang, Bin; Selway, Nichola; Shelat, Kinnari J; Dhital, Sushil; Stokes, Jason R; Gidley, Michael J

    2017-01-02

    The tribological properties of suspensions of cooked swollen starch granules are characterised for systems based on maize starch and potato starch. These systems are known as granule 'ghosts' due to the release (and removal) of polymer from their structure during cooking. Maize starch ghosts are less swollen than potato starch ghosts, resulting in a higher packing concentration and greater mechanical stability. In a soft-tribological contact, maize ghost suspensions reduce friction compared to the solvent (water), generate bell-shaped tribological profiles characteristic of particle entrainment and show a marked concentration dependence, whereas potato ghost suspensions exhibit lubrication behaviour similar to water. Microscopy analysis of the samples following tribological testing suggests that this is due to the rapid break-up of potato ghosts under the shear and rolling conditions within the tribological contact. A reduction in the small deformation moduli (associated with a weak gel structure) is also observed when the potato ghost suspensions are subjected to steady shear using parallel plate rheometry; both microscopy and particle size analysis show that this is accompanied by the partial shear-induced breakage of ghost particles. This interplay between particle microstructure and the resultant rheological and lubrication dynamics of starch ghost suspensions contributes to an enhanced mechanistic understanding of textural and other functional properties of cooked starches in food and other applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Modifying the properties of finely ground limestone by tumbling granulation

    Science.gov (United States)

    Macho, Oliver; Eckert, Maroš; Tomášová, Barbora; Peciar, Peter; Ščasný, Martin; Fekete, Roman; Peciar, Marián

    2016-06-01

    Calcium carbonate in the form of finely ground limestone is a material that has found its application in a wide range of industries, in the chemical, rubber, agricultural, and paper industries, is used for desulfurization of boilers and other. In civil engineering, ground limestone is used for the production of building materials, plaster and mortar mixtures, as a filler in concrete mixtures, in road construction, and as an essential component of mastic asphalt. This paper deals with examining the modification of the properties of finely ground limestone by the tumbling agglomeration method. It has been shown that the components of concrete with a round grain have a positive effect on the pumping of concrete in comparison with an elongated grain or the rough surface of crushed stone. The experiments will be carried out on a granulation plate using a variety of granulation liquid. The agglomerates and their properties were compared with untreated finely ground limestone, with a focus on detecting changes in compressibility, density and particle size. The output of this paper is a description and graphical representation of the changes in the properties of ground limestone before and after the agglomeration process.

  10. Human oocyte cryopreservation and the fate of cortical granules.

    Science.gov (United States)

    Ghetler, Yehudith; Skutelsky, Ehud; Ben Nun, Isaac; Ben Dor, Liah; Amihai, Dina; Shalgi, Ruth

    2006-07-01

    To examine the effect of the commonly used oocyte cryopreservation protocol on the cortical granules (CGs) of human immature germinal vesicle (GV) and mature metaphase II (MII) oocytes. Laboratory study. IVF unit. Unfertilized, intracytoplasmic sperm injected (ICSI) oocytes, and immature oocytes were cryopreserved using a slow freezing-rapid thawing program with 1,2-propanediol (PROH) as a cryoprotectant. Cortical granule exocytosis (CGE) was assessed by either confocal microscopy or transmission electron microscopy (TEM). The survival rates of frozen-thawed oocytes (mature and immature) were significantly lower compared with zygotes. Both mature and immature oocytes exhibited increased fluorescence after cryopreservation, indicating the occurrence of CGE. Mere exposure of oocytes to cryoprotectants induced CGE of 70% the value of control zygotes. The TEM revealed a drastic reduction in the amount of CGs at the cortex of frozen-thawed GV and MII oocytes, as well as appearance of vesicles in the ooplasm. The commonly used PROH freezing protocol for human oocytes resulted in extensive CGE. This finding explains why ICSI is needed to achieve fertilization of frozen-thawed human oocytes.

  11. High Plasticity of New Granule Cells in the Aging Hippocampus

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    Mariela F. Trinchero

    2017-10-01

    Full Text Available Summary: During aging, the brain undergoes changes that impair cognitive capacity and circuit plasticity, including a marked decrease in production of adult-born hippocampal neurons. It is unclear whether development and integration of those new neurons are also affected by age. Here, we show that adult-born granule cells (GCs in aging mice are scarce and exhibit slow development, but they display a remarkable potential for structural plasticity. Retrovirally labeled 3-week-old GCs in middle-aged mice were small, underdeveloped, and disconnected. Neuronal development and integration were accelerated by voluntary exercise or environmental enrichment. Similar effects were observed via knockdown of Lrig1, an endogenous negative modulator of neurotrophin receptors. Consistently, blocking neurotrophin signaling by Lrig1 overexpression abolished the positive effects of exercise. These results demonstrate an unparalleled degree of plasticity in the aging brain mediated by neurotrophins, whereby new GCs remain immature until becoming rapidly recruited to the network by activity. : Trinchero et al. show that development of new granule cells born in the adult hippocampus is strongly influenced by age. In the aging hippocampus, new neurons remain immature for prolonged intervals, yet voluntary exercise triggers their rapid growth and functional synaptogenesis. This extensive structural remodeling is mediated by neurotrophins. Keywords: adult neurogenesis, dentate gyrus, functional integration, neurotrophins, synaptogenesis, exercise

  12. Enteric coating of granules containing the probiotic Lactobacillus acidophilus

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    Pyar Hassan

    2014-06-01

    Full Text Available In the present study, a capsule formulation composed of enteric coated granules of Lactobacillus acidophilus ATCC 4962 was developed using Eudragit L30D-55 as enteric polymer. Optimization of the capsule formulation was achieved with a maximum viable cell count after 2 h of incubation in acid medium and disintegration time of 1 h in buffer pH 6.8. The amount of Eudragit L30D-55 in the capsules correlated with gastric juice resistance. The best protective qualities against artificial gastric juice were observed when capsules were prepared from granules composed of L. acidophilus, corn starch, lactose monohydrate, polyvinylpyrrolidone and coated with 12.5 % (m/V of Eudragit L30D-55. Capsule formulation of L. acidophilus in edible broth medium suspension serves as a cheap alternative to the expensive freeze-drying procedure for preparing L. acidophilus. In addition, the enteric coating using Eudragit L30D-55 could protect probiotics from the acidic gastric environment and enhance the bioactivity of probiotics along with replacement of pathogenic microbes in human intestine

  13. Biodiesel production from microbial granules in sequencing batch reactor.

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    Liu, Lin; Hong, Yuling; Ye, Xin; Wei, Lili; Liao, Jie; Huang, Xu; Liu, Chaoxiang

    2018-02-01

    Effect of reaction variables of in situ transesterification on the biodiesel production, and the characteristic differences of biodiesel obtained from aerobic granular sludge (AG) and algae-bacteria granular consortia (AAG) were investigated. The results indicated that the effect of variables on the biodiesel yield decreased in the order of methanol quantity > catalyst concentration > reaction time, yet the parameters change will not significantly affect biodiesel properties. The maximum biodiesel yield of AAG was 66.21 ± 1.08 mg/g SS, what is significant higher than that of AG (35.44 ± 0.92 mg/g SS). Although methyl palmitate was the dominated composition of biodiesel obtained from both granules, poly-unsaturated fatty acid in the AAG showed a higher percentage (21.86%) than AG (1.2%) due to Scenedesmus addition. Further, microbial analysis confirmed that the composition of biodiesel obtained from microbial granules was also determined by bacterial community, and Xanthomonadaceae and Rhodobacteraceae were the dominant bacteria of AG and AAG, respectively. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Modifying the properties of finely ground limestone by tumbling granulation

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    Macho Oliver

    2016-06-01

    Full Text Available Calcium carbonate in the form of finely ground limestone is a material that has found its application in a wide range of industries, in the chemical, rubber, agricultural, and paper industries, is used for desulfurization of boilers and other. In civil engineering, ground limestone is used for the production of building materials, plaster and mortar mixtures, as a filler in concrete mixtures, in road construction, and as an essential component of mastic asphalt. This paper deals with examining the modification of the properties of finely ground limestone by the tumbling agglomeration method. It has been shown that the components of concrete with a round grain have a positive effect on the pumping of concrete in comparison with an elongated grain or the rough surface of crushed stone. The experiments will be carried out on a granulation plate using a variety of granulation liquid. The agglomerates and their properties were compared with untreated finely ground limestone, with a focus on detecting changes in compressibility, density and particle size. The output of this paper is a description and graphical representation of the changes in the properties of ground limestone before and after the agglomeration process.

  15. State of the art of aerobic granulation in continuous flow bioreactors.

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    Kent, Timothy R; Bott, Charles B; Wang, Zhi-Wu

    In the wake of the success of aerobic granulation in sequential batch reactors (SBRs) for treating wastewater, attention is beginning to turn to continuous flow applications. This is a necessary step given the advantages of continuous flow treatment processes and the fact that the majority of full-scale wastewater treatment plants across the world are operated with aeration tanks and clarifiers in a continuous flow mode. As in SBRs, applying a selection pressure, based on differences in either settling velocity or the size of the biomass, is essential for successful granulation in continuous flow reactors (CFRs). CFRs employed for aerobic granulation come in multiple configurations, each with their own means of achieving such a selection pressure. Other factors, such as bioaugmentation and hydraulic shear force, also contribute to aerobic granulation to some extent. Besides the formation of aerobic granules, long-term stability of aerobic granules is also a critical issue to be addressed. Inorganic precipitation, special inocula, and various operational optimization strategies have been used to improve granule long-term structural integrity. Accumulated studies reviewed in this work demonstrate that aerobic granulation in CFRs is capable of removing a wide spectrum of contaminants and achieving properties generally comparable to those in SBRs. Despite the notable research progress made toward successful aerobic granulation in lab-scale CFRs, to the best of our knowledge, there are only three full-scale tests of the technique, two being seeded with anammox-supported aerobic granules and the other with conventional aerobic granules; two other process alternatives are currently in development. Application of settling- or size-based selection pressures and feast/famine conditions are especially difficult to implement to these and similar mainstream systems. Future research efforts needs to be focused on the optimization of the granule-to-floc ratio, enhancement of

  16. The functional morphology of color changing in a spider: development of ommochrome pigment granules.

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    Insausti, Teresita C; Casas, Jérôme

    2008-03-01

    Studies on the formation of ommochrome pigment granules are very few, despite their generalized occurrence as screening pigments in insect eyes. This is particularly true for ommochrome granules responsible for epidermal coloration. The aims of this study were to characterize the localization of major body pigments in a color changing mimetic spider, Misumena vatia (Thomisidae), and to describe the formation and location of ommochrome pigment granules responsible for the spider's color change from white to yellow. The unpigmented cuticula of this spider is transparent. Both the guanine localized in guanine cells in the opisthosoma and the uric acid localized in epidermis cells in the prosoma are responsible for the white coloration. The bright yellow color is due to the combination of ommochrome pigment granules and the white reflectance from coincident guanine and/or uric acid. The formation of ommochrome pigment granules in epidermis cells proceeds via three distinctive steps. Translucent, UV fluorescent, progranules (type I) are produced by a dense network of endoplasmic reticulum associated with numerous mitochondria and glycogen rosettes. These progranules are present in white spiders only, and regularly distributed in the cytoplasm. The merging of several progranules of type I into a transient state (progranule type II) leads to the formation of granules (type III) characterized by their lack of fluorescence, their spherical sections and their osmophilic-electron-dense contents. They are found in yellow spiders and in the red stripes on the body sides. Their color varies from yellow to red. Thus, white spiders contain only type I granules, yellow tinted spiders contain type II and III granules and bright yellow spiders contain only type III granules. We present a synthetic view of the ontogeny of ommochrome granules. We discuss the physiology of color changing and the nature of the chemical compounds in the different types of granules. Extended studies on the

  17. Preparation of porcelain tile granulates by more environmentally sustainable processes

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    García-Ten, J.

    2012-04-01

    Full Text Available This study examines the feasibility of manufacturing glazed porcelain tiles with a more environmentally friendly manufacturing process, by reducing water and thermal energy consumption. The process studied in this paper is dry milling in a pendulum mill, with subsequent granulation (in order to obtain a press powder with similar flowability to that of spraydried powders. The different morphology of the new granulate with respect to the standard spray-dried granulate modifies the microstructure of the green compacts and thus, their behaviour and fired tile properties. In order to obtain porcelain tiles with the required properties (water absorption, mechanical strength,… changes have been made in the raw materials mixture and in the processing variables. Finally, porcelain tiles measuring 50x50 cm have been manufactured at industrial scale with the new granulate using a conventional firing cycle, obtaining quality levels identical to those provided by the spray-dried granulate. These results open the possibility of preparing porcelain tile body compositions through a manufacturing process alternative to the standard one, more environmentally friendly and with lower costs.

    En el presente trabajo se ha estudiado la viabilidad de fabricar gres porcelánico esmaltado utilizando un sistema de preparación de la composición del soporte más respetuoso con el medio ambiente, lo que implica una reducción importante de los consumos de agua y de energía térmica. El proceso que se estudia en el presente trabajo es el consistente en la molienda vía seca en molino pendular y en la posterior granulación (para obtener un polvo de prensas con fluidez similar a la de los polvos atomizados. La distinta morfología de los nuevos gránulos obtenidos respecto al polvo atomizado actual, modifica la microestuctura en crudo de las piezas y, con ello, el comportamiento y propiedades finales de las baldosas obtenidas. Por ello, ha sido necesario

  18. Difference in distribution of membrane proteins between low- and high-density secretory granules in parotid acinar cells

    International Nuclear Information System (INIS)

    Fujita-Yoshigaki, Junko; Katsumata, Osamu; Matsuki, Miwako; Yoshigaki, Tomoyoshi; Furuyama, Shunsuke; Sugiya, Hiroshi

    2006-01-01

    Secretory granules (SGs) are considered to be generated as immature granules and to mature by condensation of their contents. In this study, SGs of parotid gland were separated into low-, medium-, and high-density granule fractions by Percoll-density gradient centrifugation, since it was proposed that the density corresponds to the degree of maturation. The observation with electron microscopy showed that granules in the three fractions were very similar. The average diameter of high-density granules was a little but significantly larger than that of low-density granules. Although the three fractions contained amylase, suggesting that they are all SGs, distribution of membrane proteins was markedly different. Syntaxin6 and VAMP4 were localized in the low-density granule fraction, while VAMP2 was concentrated in the high-density granule fraction. Immunoprecipitation with anti-syntaxin6 antibody caused coprecipitation of VAMP2 from the medium-density granule fraction without solubilization, but not from Triton X-100-solubilized fraction, while VAMP4 was coprecipitated from both fractions. Therefore, VAMP2 is present on the same granules, but is separated from syntaxin6 and VAMP4, which are expected to be removed from immature granules. These results suggest that the medium-density granules are intermediates from low- to high-density granules, and that the membrane components of SGs dynamically change by budding and fusion during maturation

  19. Sonic hedgehog-induced histone deacetylase activation is required for cerebellar granule precursor hyperplasia in medulloblastoma.

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    Seung Joon Lee

    Full Text Available Medulloblastoma, the most common pediatric brain tumor, is thought to arise from deregulated proliferation of cerebellar granule precursor (CGP cells. Sonic hedgehog (Shh is the primary mitogen that regulates proliferation of CGP cells during the early stages of postnatal cerebellum development. Aberrant activation of Shh signaling during this time has been associated with hyperplasia of CGP cells and eventually may lead to the development of medulloblastoma. The molecular targets of Shh signaling involved in medulloblastoma formation are still not well-understood. Here, we show that Shh regulates sustained activation of histone deacetylases (HDACs and that this activity is required for continued proliferation of CGP cells. Suppression of HDAC activity not only blocked the Shh-induced CGP proliferation in primary cell cultures, but also ameliorated aberrant CGP proliferation at the external germinal layer (EGL in a medulloblastoma mouse model. Increased levels of mRNA and protein of several HDAC family members were found in medulloblastoma compared to wild type cerebellum suggesting that HDAC activity is required for the survival/progression of tumor cells. The identification of a role of HDACs in the early steps of medulloblastoma formation suggests there may be a therapeutic potential for HDAC inhibitors in this disease.

  20. Semaphorin 5A inhibits synaptogenesis in early postnatal- and adult-born hippocampal dentate granule cells.

    Science.gov (United States)

    Duan, Yuntao; Wang, Shih-Hsiu; Song, Juan; Mironova, Yevgeniya; Ming, Guo-li; Kolodkin, Alex L; Giger, Roman J

    2014-10-14

    Human SEMAPHORIN 5A (SEMA5A) is an autism susceptibility gene; however, its function in brain development is unknown. In this study, we show that mouse Sema5A negatively regulates synaptogenesis in early, developmentally born, hippocampal dentate granule cells (GCs). Sema5A is strongly expressed by GCs and regulates dendritic spine density in a cell-autonomous manner. In the adult mouse brain, newly born Sema5A-/- GCs show an increase in dendritic spine density and increased AMPA-type synaptic responses. Sema5A signals through PlexinA2 co-expressed by GCs, and the PlexinA2-RasGAP activity is necessary to suppress spinogenesis. Like Sema5A-/- mutants, PlexinA2-/- mice show an increase in GC glutamatergic synapses, and we show that Sema5A and PlexinA2 genetically interact with respect to GC spine phenotypes. Sema5A-/- mice display deficits in social interaction, a hallmark of autism-spectrum-disorders. These experiments identify novel intra-dendritic Sema5A/PlexinA2 interactions that inhibit excitatory synapse formation in developmentally born and adult-born GCs, and they provide support for SEMA5A contributions to autism-spectrum-disorders.