Proton pump inhibitors and histamine-2-receptor antagonists and pancreatic cancer risk: a nested case-control study

Background: The relationship between use of proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H₂RAs) and pancreatic cancer risk has yet to be examined. Data from a range of studies suggest biologically plausible mechanisms, whereby these drugs (or the conditions for which they are prescribed) may affect pancreatic cancer risk. The objective of this study was to investigate the relationship between use of PPIs/H₂RAs and pancreatic cancer risk.

Methods: A nested case – control study was conducted within the UK general practice research database (GPRD). Cases had a diagnosis of exocrine pancreatic cancer and controls were matched to cases on general practice site, sex and year of birth. Exposure to PPIs and to H₂RAs since entry into GPRD until 2 years before the diagnosis date (corresponding date in controls) and in the 5 years before the diagnosis date were separately assessed. Conditional logistic regression analyses were used to generate odds ratios (ORs) and 95% confidence intervals (CIs) associated with PPI or H₂RA use compared with nonuse.

Results: Ever use of PPIs since entry into the GPRD (excluding the 2 years prior to diagnosis) was not associated with risk of pancreatic cancer; OR (95% CI) 1.02 (0.85 – 1.22). Neither the dose nor the duration of PPI or H₂RA use was associated with pancreatic cancer risk. No consistent patterns of association were seen when cumulative exposure (dose and duration) to these drugs was examined separately or together.

Conclusion: PPI/H₂RA use, in a UK population, was not associated with pancreatic cancer risk.

Anti-inflammatory effects of DX-890, a human neutrophil elastase inhibitor

Background
Neutrophil elastase (NE)-mediated inflammation contributes to lung damage in cystic fibrosis (CF). We investigated if DX-890, a small-protein NE inhibitor, could reduce neutrophil trans-epithelial migration and reduce activity released from neutrophils and NE-induced cytokine expression in airway epithelial cells.

Methods
Activated blood neutrophils (CF and healthy) treated ± DX-890 were assayed for NE activity. Transmigration of calcein-labeled neutrophils was studied using a 16HBE14o- epithelial monolayer. IL-8 release from primary nasal epithelial monolayers (CF and healthy) was measured after treatment ± DX-890 and NE or CF sputum.

Results
DX-890 reduced NE activity from neutrophils (CF and healthy) and reduced neutrophil transmigration. DX-890 pre-treatment reduced IL-8 release from epithelial cells of healthy or CF subjects after stimulation with NE and CF sputum sol. All improvements with DX-890 were statistically significant (p < 0.05).

Conclusions
DX-890 reduces NE-mediated transmigration and inflammation. NE inhibition could be useful in managing neutrophilic airway inflammation in CF.

ULTRASTRUCTURAL-LOCALIZATION OF PANCREATIC POLYPEPTIDE AND FMRFAMIDE IMMUNOREACTIVITIES WITHIN THE CENTRAL-NERVOUS-SYSTEM OF THE NEMATODE, ASCARIS-SUUM (NEMATODA, ASCAROIDEA)

A post-embedding immunogold technique has been used to examine the subcellular distribution of immunoreactivities to vertebrate pancreatic polypeptide (PP) and to the invertebrate peptide, FMRFamide within the central nervous system (CNS) of the nematode, Ascaris suum. Gold labelling of peptide was localized exclusively over dense-cored vesicles within nerve cell bodies, nerve axons and nerve terminals of the main ganglia and nerve cords in the CNS. Double-labelling of peptides demonstrated an apparent co-localization of PP and FMRFamide immunoreactivities in the same dense-cored vesicles, although populations of dense-cored vesicles that labelled solely for FMRFamide were also evident. Antigen preabsorption studies indicated little or no cross-reactivity between the two antisera.

ULTRASTRUCTURAL-LOCALIZATION OF FMRFAMIDE-IMMUNOREACTIVITY AND PANCREATIC POLYPEPTIDE-IMMUNOREACTIVITY WITHIN THE CENTRAL-NERVOUS-SYSTEM OF THE LIVER FLUKE, FASCIOLA-HEPATICA (TREMATODA, DIGENEA)

A post-embedding immunogold technique was used to examine the subcellular distribution of immunoreactivities to the invertebrate peptide, FMRFamide, and to vertebrate pancreatic polypeptide (PP) within the central nervous system of the trematode, Fasciola hepatica. Gold labeling of peptide was localised exclusively over both dense-cored and ellipsoidal electron-dense vesicles (with a homogeneous matrix) present within nerve cell bodies, small and 'giant' nerve processes of the neuropile in the cerebral ganglia and transverse commissure, as well as in the main longitudinal nerve cords. Double labeling demonstrated an apparent co-localisation of FMRFamide and PP immunoreactivities in the same dense-cored vesicles, although populations of ellipsoidal electron-dense vesicles that labeled solely for FMRFamide were also evident. Antigen pre-absorption studies indicated little, if any, cross-reactivity of the two antisera.

CHROMATOGRAPHIC AND IMMUNOLOGICAL CHARACTERIZATION OF NEUROPEPTIDE Y-LIKE AND PANCREATIC POLYPEPTIDE-LIKE PEPTIDES FROM THE NEMATODE ASCARIS-SUUM

1. Immunoreactivity (IR) towards neuropeptide Y (NPY) and pancreatic polypeptide (PP) has previously been demonstrated in nematodes by immunocytochemistry (ICC).

ISOLATION AND PARTIAL SEQUENCING OF A PANCREATIC POLYPEPTIDE-LIKE NEUROPEPTIDE FROM THE LIVER FLUKE, FASCIOLA-HEPATICA

1. A pancreatic polypeptide (PP)-immunoreactive neuropeptide has been isolated and partially sequenced from the liver fluke, Fasciola hepatica.

THE ULTRASTRUCTURE AND IMMUNOGOLD LABELING OF PANCREATIC POLYPEPTIDE-IMMUNOREACTIVE CELLS ASSOCIATED WITH THE EGG-FORMING APPARATUS OF A MONOGENEAN PARASITE, DICLIDOPHORA-MERLANGI

An electron microscopical examination has been made of the fine structure and disposition of pancreatic polypeptide immunoreactive cells associated with the egg-forming apparatus in Diclidophora merlangi. The cell bodies are positioned in the parenchyma surrounding the ootype and taper to axon-like processes that extend to the ootype wall. The terminal regions of these processes branch and anastomose and, in places, the swollen endings or varicosities form synaptic appositions with the muscle fibres in the ootype wall. The cells are characterized by an extensive GER-Golgi system that is involved in the assembly and packaging of dense-cored vesicles. The vesicles accumulate in the axons and terminal varicosities, and their contents were found to be immunoreactive with antisera raised to the C-terminal hexapeptide amide of pancreatic polypeptide. It is concluded that the cells are neurosecretory in appearance and that, functionally, their secretions may serve to regulate ootype motility and thereby help co-ordinate egg production in the worm.