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  • 1
    Electronic Resource
    Electronic Resource
    Oxford UK : Blackwell Science Ltd.
    Alimentary pharmacology & therapeutics 16 (2002), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Altered visceral perception is common in functional dyspepsia (FD). Dopaminergic pathways control gastrointestinal motility, but whether they modulate visceral sensitivity is unknown.〈section xml:id="abs1-2"〉〈title type="main"〉Aim:To investigate whether levosulpiride, a D2 antagonist, modulates gastric sensitivity and compliance in dyspeptic patients.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Eight healthy subjects and 16 dyspeptic patients underwent graded gastric distensions using a tensostat. In dyspeptic patients the same isotonic distensions were repeated during either levosulpiride or saline administration. Eight FD patients were evaluated after 4-week treatment with oral levosulpiride. Gastrointestinal symptoms were evaluated using a 100 mm visual analogue score. Perception was scored on a scale of 0 to 6.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Although healthy subjects and FD patients had similar gastric compliance, FD patients tolerated lower tension levels. At the same distending tension levels, levosulpiride decreased gastric compliance and perception score (14 ± 6% and 38 ± 10% change, respectively; P 〈 0.05 vs. saline) only in FD patients. Isotonic distensions exhibited very reproducible perception. Chronic levosulpiride administration significantly reduced dyspeptic symptoms and increased discomfort threshold.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:Compared with healthy subjects, FD patients show marked gastric hypersensitivity. In FD patients levosulpiride decreased the perception of gastric distension with an action unrelated to change of gastric tone. Chronic levosulpiride administration significantly ameliorates gastrointestinal symptoms and increases the discomfort threshold.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford UK : Blackwell Science Ltd.
    Alimentary pharmacology & therapeutics 11 (1997), S. 0 
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Margination of circulating neutrophils (PMN) into the gastric microcirculation is an early and critical event in the pathogenesis of non-steroidal antinflammatory drug (NSAID)-induced gastropathy. This effect is mediated through the upregulation of β2 integrins on the PMN surface.〈section xml:id="abs1-2"〉〈title type="main"〉Aims:To investigate whether indomethacin modulates: (1) Mac-1 expression; (2) Ca2+ mobilization ([Ca2+]i), protein kinase C and nitric oxide accumulation; and (3) mitogen-associated protein kinase phosphorylation in human PMN.〈section xml:id="abs1-3"〉〈title type="main"〉Methods:Human PMN were isolated by centrifugation through a double Ficoll gradient. [Ca2+]i was measured in PMN loaded with fura-2 and Mac-1 expression by flow cytometry.〈section xml:id="abs1-4"〉〈title type="main"〉Results:Indomethacin caused a concentration- and time-dependent upregulation of CD11b and CD18 expression and PMN adhesion to endothelial cells. Maximal upregulation of Mac-1 expression (40–50%) occurred after a 30-min incubation with 0.1 mM indomethacin. The effect was prevented by removing the Ca2+. Ionomycin and thapsigargin caused a 7–10-fold increase in [Ca2+]i and a 2–4-fold increase in Mac-1 expression. Indomethacin induced a concentration-dependent phosphorylation of a 41-kDa mitogen-associated protein kinase. Tyrosine kinase inhibitors prevented the effect of indomethacin on Mac-1 expression and Ca2+ mobilization. Indomethacin and ionomycin increased superoxide generation, myeloperoxidase secretion and PMN adherence to endothelial cells and stimulated nitric oxide production. Indomethacin-induced Mac-1 upregulation was prevented by a nitric oxide synthase inhibitor.〈section xml:id="abs1-5"〉〈title type="main"〉Conclusions:Indomethacin-induced upregulation of Mac-1 is mediated by changes in [Ca2+]i and nitric oxide. Phosphorylation of the 41-kDa mitogen-associated protein isoform is a previously unreported target of NSAID action. These effects might help to explain the ability of indomethacin to cause gastric neutrophil margination.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0009-8981
    Keywords: Alcoholic hepatitis ; Chronic hepatitis ; Hepatic fibrosis ; PZ-Peptidase ; Procollagen III
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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