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  • 1
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  Delta virus (HDV)-related chronic hepatitis is difficult to treat.Aims:  To evaluate the efficacy of lamivudine 100 mg daily on serum HDV-RNA, hepatitis D virus antibodies and alanine aminotransferase levels, liver histology, and on hepatitis B surface antigen seroconversion.Methods:  Thirty-one hepatitis B surface antigen-positive, HDV-RNA-positive patients with ALT ≥ 1.5 upper normal level and compensated liver disease were randomized (1:2 ratio) to placebo (group A, n = 11) or lamivudine (group B, n = 20) for 52 weeks; thereafter, all patients were given lamivudine for 52 weeks and followed up for 16 weeks.Results:  Twenty-five patients (81%) completed the study. No patient was HDV-RNA-negative at week 52; three patients (11%) were negative at week 104. Two of them remained HDV-RNA-negative at week 120, and one lost the hepatitis B surface antigen without seroconversion. Paired pre-treatment and week 104 liver biopsies were available from 19 patients: of which three of seven (43%) from group A and two of 12 patients (17%) from group B had a ≥2 point decrease in the Ishak necroinflammatory score.Conclusion:  A sustained complete response was achieved in 8% of hepatitis D virus-infected patients treated with lamivudine and a partial histological response in 26% of them. Hepatitis D virus viraemia was unaffected, even in patients when hepatitis B virus replication was lowered by lamivudine therapy.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1523-5378
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background and Aims.  H. pylori infection results in an increased epithelial apoptosis in gastritis and duodenal ulcer patients. We investigated the role and type of activation of caspases in H. pylori-induced apoptosis in gastric epithelial cells.Methods.  Differentiated human gastric cancer cells (AGS) and human gastric mucous cell primary cultures were incubated with H. pylori for 0.5–24 hours in RPMI 1640 medium, and the effects on cell viability, epithelial apoptosis, and activity of caspases were monitored. Apoptosis was analyzed by detection of DNA-fragments by Hoechst stain®, DNA-laddering, and Histone-ELISA. Activities of caspases were determined in fluorogenic assays and by Western blotting. Cleavage of BID and release of cytochrome c were analyzed by Western blot. Significance of caspase activation was investigated by preincubation of gastric epithelial cells with cell permeable specific caspase inhibitors.Results.  Incubation of gastric epithelial cells with H. pylori caused a time and concentration dependent induction of DNA fragmentation (3-fold increase), cleavage of BID, release of cytochrome c and a concomittant sequential activation of caspase-9 (4-fold), caspase-8 (2-fold), caspase-6 (2-fold), and caspase-3 (6-fold). No effects on caspase-1 and -7 were observed. Activation of caspases preceded the induction of DNA fragmentation. Apoptosis could be inhibited by prior incubation with the inhibitors of caspase-3, -8, and -9, but not with that of caspase-1.Conclusions.  Activation of certain caspases and activation of the mitochondrial apoptotic pathway are essential for H. pylori induced apoptosis in gastric epithelial cells.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Allergy 51 (1996), S. 0 
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The role of allergic reactions in the pathogenesis of inflammatory bowel disease and irritable bowel syndrome has been disputed. This study aimed to determine the prevalence of adverse reactions to food in patients with gastrointestinal disease. A total of 375 adult patients of a gastroenterologic outpatient clinic were examined by history, skin tests, measurements of laboratory parameters, and intestinal provocation with food allergens by colonoscopy. Some 32% complained of adverse reactions to food as a cause of their abdominal symptoms. In 14.4%, the diagnosis of intestinal food allergy could be suspected according to several criteria such as elevated total IgE, specific IgE against food antigens, eosinophilia, responsiveness to cromoglycate, and clinical signs of atopic disease. In 3.2%, the diagnosis could be confirmed by endoscopic allergen provocation and/or elimination diet and rechallenge. In conclusion, the data suggest that allergic reactions to food antigens may be a causative factor in a subgroup of patients with inflammatory and functional gastrointestinal disease.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1398-9995
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background:  The mechanisms of gastrointestinal (GI) food allergy (FA) are poorly understood. Immunoglobulin E (IgE) is increased in stools from patients with FA, as well as the number of cells carrying IgE in intestinal mucosa, but the origin of IgE production remains unknown. To investigate a local production of IgE in intestine, we analysed the levels of transcripts for epsilon germ-line (εGT), and potential regulators of IgE production, IL-4, IL-13, IFN-γ, IL-4Rα, STAT6 and FcεRIα in intestinal mucosa of adult patients with FA.Methods:  Endoscopic biopsies were obtained from the caecum of 25 patients with FA and 14 control patients. The levels of εGT, IL-4, IL-13, IFN-γ, IL-4Rα, STAT6 and FcεRIα mRNA were analysed by real-time RT-PCR and compared with unpaired nonparametric Mann–Whitney test.Results:  The mean εGT transcript level in caecum was increased in FA patients compared with control patients (P 〈 0.05). IL-4 mRNA expression was also increased in FA patients (P 〈 0.05), whereas mRNA expression for IL-13, IFN-γ, IL-4Rα, STAT6 and FcεRIα mRNA expression was not altered. However, the ratio of IL-4 mRNA/IFN-γ mRNA was significantly increased in FA patients (P 〈 0.05). No correlation was observed between εGT transcripts expression in intestinal mucosa and total IgE levels in serum.Conclusions:  This study shows that (i) εGT transcripts are expressed in human intestinal mucosa; (ii) εGT and IL-4 transcripts are increased in caecal mucosa from patients with FA. These results suggest local production of IgE in intestine that might be of importance for inflammatory reactions in the GI tract.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2222
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background IgE-dependent activation of mast cells (MCs) is a key pathomechanism of type I allergies. In contrast, allergen-specific IgG Abs are thought to attenuate immediate allergic reactions by blocking IgE binding and by cross-linking the inhibitory Fcγ receptor IIB on MCs.Objectives To establish a defined in vitro system using human MCs to study the biological activity of allergens and to investigate the role of allergen-specific IgE and IgG.Methods Purified human intestinal MCs sensitized with different forms of specific IgE Abs were triggered by monomeric and oligomeric forms of recombinant Bet v 1, the major birch pollen allergen, in the presence or absence of allergen-specific IgG Abs.Results MCs sensitized with an anti-Bet v 1 IgE mAb or sera obtained from birch pollen allergic patients released histamine and sulphidoleukotrienes after exposure to oligomeric Bet v 1. Monomeric Bet v 1 provoked mediator release only in MCs sensitized with patients sera but not in MCs sensitized with anti-Bet v 1 IgE mAb. Interestingly, MC activation could be induced by supercross-linking of monomeric Bet v 1 bound to monovalent IgE on MCs with a secondary allergen-specific IgG pAb. By using IgG F(ab′)2 fragments we provide evidence that this effect is not a result of IgG binding to Fcγ receptors.Conclusion This assay represents a new tool for the in vitro study of MC activation in response to natural and genetically modified allergens. Fcɛ receptor I supercross-linking by allergen-specific IgG Abs provides a possible new mechanism of IgG-dependent enhancement of type I allergic reactions.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Lipids and Lipid Metabolism 1125 (1992), S. 13-20 
    ISSN: 0005-2760
    Keywords: (Rat liver) ; Carrier mediated transport ; Fatty acid ; Membrane fatty acid binding protein ; Monoclonal antibody
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 182 (1992), S. 617-623 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Naunyn-Schmiedeberg's archives of pharmacology 288 (1975), S. 215-231 
    ISSN: 1432-1912
    Keywords: Perfused Rabbit Heart ; Noradrenaline ; Tricyclic Drugs ; Arrhythmias ; Noradrenaline Uptake
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary 1. Isolated rabbit hearts were perfused with a modified Tyrode solution containing noradrenaline in concentrations increasing stepwise from 5.9 nM to 5.9 μM at 5 min intervals. This dose regime was applied twice before and once 20 min after starting perfusion with one of 9 tricyclic drugs. Ventricular rate and right atrial and ventricular tensions were recorded using the transverse method. 2. Infusions of noradrenaline evoked ventricular arrhythmias in hearts perfused with amitriptyline 4.8 μM, chlorpromazine 5.0 μM, desipramine 5.0 μM, dibenzepine 34.7 μM, doxepin 4.7 μM, imipramine 4.7 μM, noxiptiline 9.1 μM and opipramole 9.2 μM. The incidence of arrhythmias increased with the concentration of noradrenaline applied and the dose of tricyclic drug administered. Whenever arrhythmias had started they continued as long as noradrenaline was infused. Noradrenaline failed to produce arrhythmias in hearts not exposed to drugs and after iprindole 4.7 μM or cocaine 2.9–18 μM. 3. Propranolol 0.1 μM inhibited the incidence of arrhythmias after doxepin 4.7 μM plus noradrenaline 5.9–190 nM. 4. Neuronal uptake of exogenous noradrenaline in the rabbit heart was inhibited by the tricyclic drugs in the following order of declining potency: doxepin, noxiptiline, amitriptyline, desipramine, chlorpromazine, imipramine, dibenzepine, opipramole and iprindole. 5. Among tricyclic drugs the potency to inhibit amine uptake is related to the incidence of arrhythmias evoked by a submaximal concentration of noradrenaline. It appears, however, that these two parameters are not causally linked. 6. The isolated rabbit heart perfused with noradrenaline might be used as a model for testing the arrhythmogenic actions of tricyclic drugs and the treatment of such arrhythmias.
    Type of Medium: Electronic Resource
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  • 9
    ISSN: 1432-1440
    Keywords: Gastrointestinal tumors ; Cytokine ; Biotherapy ; Interferon-α ; Interleukin-2
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Over the past 20 years the administration of cytokines has emerged as an important fourth modality for the treatment of human cancer. Advances in the field of therapy of gastrointestinal tumors have become a major focus of current research, given the lack of progress of conventional antineoplastic therapy in most of these tumors. Among the heterogeneous group of gastrointestinal malignancies, novel therapeutic strategies have been employed for each individual tumor type, and cytokines (interferon-a) have gained an established role in the treatment of advanced carcinoid tumors. Although our understanding of the mechanisms of biological response modification is still limited, further improvement in the management of gastrointestinal malignancies can be expected from multimodality therapy regimens employing cytokines in combination with other biological response modifiers, chemotherapeutic agents, active-specific immunotherapy, and immunotoxin- and radionuclide-conjugated monoclonal antibodies. A wide range of clinical and preclinical studies have been conducted in colorectal carcinoma; however, potential therapeutic benefit of cytokine-based biotherapy has not been fully defined. Therefore, large-scale, i.e., multicenter, studies are required to quantify the potential therapeutic effects of cytokines in gastrointestinal tumors.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 56 (1978), S. 1179-1183 
    ISSN: 1432-1440
    Keywords: Digoxin ; Digitoxin ; Intoxikation ; Hämoperfusion mit beschichteter Aktivkohle ; Hämodialyse ; Entgiftung ; Digoxin ; digitoxin ; intoxication ; activated charcoal ; hemoperfusion ; hemodialysis ; detoxification
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Since there is no widely used causal means of reducing the severity of massive digitalis intoxication the capability of hemoperfusion with coated activated charcoal to remove toxicologically relevant amounts of digoxin and digitoxin was evaluated in vitro and in man. At a blood flow rate of 100 ml/min the digoxin clearance by hemoperfusion in vitro was 51±8 ml/min in comparison to 24.3±11.3 ml/min by hemodialysis. The average hemoperfusion clearance of digitoxin was 31.7±13.4 ml/min, whereas almost no digitoxin was removed by hemodialysis. These clearance values point to the ability of hemoperfusion of eliminating digitalis glycosides from the blood. They do not clarify the essential question whether it is possible to lower the toxic concentrations in the tissues. In two patients being on hemoperfusion for other reasons, 0.5 mg digoxin were injected intravenously as a bolus 1 h prior to the beginning of hemoperfusion and 0.125 mg/h were infused continuously over 4h simultaneously with hemoperfusion. By an average digoxin clearance of 77 ml/min, only 5 and 4.5% of the dose given were removed by this procedure. In 2 patients receiving digitoxin under the same trial conditions an average of 24% of the digitoxin load were eliminated by 4 to 6 h hemoperfusion period although the clearance values obtained were below the clearance for digoxin. The lack of effectiveness in eliminating toxicological relevant amounts of digoxin is due to the quite high distribution volume which results in high tissue concentrations and low blood concentrations of the drug. On the other hand the effective removal of digitoxin is due to the appreciably smaller distribution volume and suggests that hemoperfusion may be a valuable method of rapid reversal of advanced digitoxin toxicity in man.
    Notes: Zusammenfassung Bisher gibt es keine allgemein anwendbare kausale Therapie lebensbedrohlicher Digitalis-Intoxikationen. Daher wurde in vitro und in vivo beim Menschen untersucht, ob die Hämoperfusion mit beschichteter Aktivkohle toxikologisch relevante Mengen von Herzglykosiden zu eliminieren vermag. Bei einer Blutumlaufgeschwindigkeit von 100 ml/min betrug in vitro die Digoxin-Clearance durch Hämoperfusion 51±8 ml/min, im Vergleich zu 24,3±11,3 ml/min durch die Hämodialyse. Für Digitoxin fand sich eine Clearance von 31,7±13,4 ml/min durch Hämoperfusion, während bei Hämodialyse kein meßbarer Anteil des Glykosids eliminiert wurde. Diese Clearence-Werte lassen erwarten, daß die Herzglykoside durch die Hämoperfusion aus dem Blut eliminiert werden, ohne daß allerdings durch die in vitro-Untersuchung eine Aussage möglich ist, ob toxische Glykosidkonzentrationen im Gewebe hierdurch gesenkt werden können. Bei 2 Patienten, bei denen aus anderen Gründen eine Hämoperfusion durchgeführt wurde, wurde Digoxin nach einer Bolusinjektion von 0,5 mg mit einer konstanten Geschwindigkeit von 0,125 ml/h infundiert und der Effekt der Hämoperfusion ermittelt. Bei einer mittleren Digoxin-Clearance von 77 ml/min wurden durch eine 4- bzw. 6-stündige Hämoperfusion nur 5% und 4,5% der applizierten Dosis eliminiert. Dahingegen wurden bei gleichem Vorgehen bei 2 anderen Patienten im Mittel 24% der verabreichten Digitoxin-Dosis durch eine 4- bzw. 6stündige Hämoperfusion eliminiert, obwohl die Digitoxin-Clearance deutlich unter der Digoxin-Clearance lag. Die geringe Effektivität der Hämoperfusion bei der Digoxinelimination ist auf das große Verteilungsvolumen dieses Glykosids zurückzuführen, welches durch hohe Gewebe-und niedrige Plasmakonzentrationen gekennzeichnet ist. Andererseits ist die gute Wirkung der Hämoperfusion in der Elimination von Digitoxin auf das deutlich kleinere Verteilungsvolumen zurückzuführen und läßt den Einsatz der Hämoperfusion bei lebensbedrohlicher Digitoxin-Intoxikation sinnvoll erscheinen.
    Type of Medium: Electronic Resource
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