Search Results - (Author, Cooperation:E. F. Stange)

2011-01-21

Nature Publishing Group (NPG)

0028-0836

1476-4687

Biology

Chemistry and Pharmacology

Medicine

Natural Sciences in General

Physics

Amino Acid Sequence ; Anti-Infective Agents/chemistry/immunology/*metabolism/*pharmacology ; Bifidobacterium/drug effects/immunology ; Biocatalysis ; Candida albicans/drug effects/immunology ; Colon/immunology/metabolism/microbiology ; Disulfides/chemistry/*metabolism ; Dithiothreitol/pharmacology ; Humans ; Immunity, Innate ; Intestinal Mucosa/immunology/metabolism/microbiology ; Lactobacillus/drug effects/immunology ; Molecular Sequence Data ; Oxidation-Reduction/drug effects ; Oxygen/metabolism ; Partial Pressure ; Protein Conformation/drug effects ; Thioredoxins/metabolism ; beta-Defensins/chemistry/immunology/*metabolism/*pharmacology

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Background : 6-Thioguanine-nucleotides seem to be the active metabolites of thiopurine therapy, and their monitoring has been considered a useful tool for optimizing response in inflammatory bowel diseases. Tioguanine (thioguanine) therapy results in much higher levels of 6-thioguanine-nucleotide levels when compared with azathioprine or mercaptopurine.Aim : To elucidate the influence of 6-thioguanine-nucleotide and methylated 6-thioguanine-nucleotide levels under tioguanine on efficacy and toxicity in Crohn's disease.Methods : 6-Thioguanine-nucleotide and methylated 6-tioguanine-nucleotide levels were measured regularly in 26 Crohn's disease patients treated with tioguanine. Nucleotide levels were related to efficacy and toxicity.Results : 6-Thioguanine-nucleotide levels rose very high [median 1241 pmol/8 × 108 red blood cells (range 313–1853)]. Methylated 6-thioguanine-nucleotide levels were detected in all patients [491 pmol/8 × 108 red blood cells (154–1775)]. 6-Thioguanine-nucleotide and methylated 6-thioguanine-nucleotide concentrations correlated significantly (r = 0.7, P 〈 0.0001). Nucleotide levels from patients achieving remission (n = 14) did not differ significantly from non-remitters (n = 12) [6-thioguanine-nucleotide: 1077 (599–2160) vs. 1210 (534–4665); methylated 6-thioguanine-nucleotide: 510 (214–1222) vs. 421 (145–1284)]. One patient with intermediate thiopurine S-methyltransferase activity experienced bone marrow toxicity upon dose escalation parallel with excessively high thioguanine-nucleotide levels.Conclusions : 6-Thioguanine-nucleotide as well as methylated 6-thioguanine-nucleotide levels under tioguanine therapy were not related to efficacy. This suggests that monitoring of 6-thioguanine-nucleotide levels is not a useful tool to predict response to thiopurines.

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1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Conflicting data exist about proteinuria in inflammatory bowel diseases. It is still unclear whether the occurrence of proteinuria in inflammatory bowel disease patients is an extra-intestinal manifestation of disease or the result of adverse effects to medication, especially to aminosalicylates (ASA).〈section xml:id="abs1-2"〉〈title type="main"〉Methods:A total of 95 patients (51 with Crohn’s disease and 44 with ulcerative colitis) were enrolled in the study. Disease activity was assessed by Crohn’s Disease Activity Index (CDAI) or the Truelove index, respectively. Urine was collected over 24 h and protein excretion of specific marker proteins for tubular (α1-microglobulin-α1-MG) and glomerular (albumin-Alb, Immunoglobulin G-IgG) dysfunction was measured using a highly sensitive immunoluminometric assay.〈section xml:id="abs1-3"〉〈title type="main"〉Results:Out of 51 Crohn’s disease patients, 20 showed elevated urinary α1-MG. The amount of α1-MGuria was strongly correlated to the CDAI (r=0.6, P 〈 0.001). Only four Crohn’s disease patients showed slightly elevated values for glomerular proteins in urine. Similar results were obtained for ulcerative colitis: whereas only two ulcerative colitis patients showed albuminuria, tubular proteinuria was detected in 28 out of 44 ulcerative colitis patients. Proteinuria was strongly dependent on disease activity (P 〈 0.01) but was not related to ASA treatment.〈section xml:id="abs1-4"〉〈title type="main"〉Conclusions:Proteinuria of tubular marker proteins occurs in the majority of inflammatory bowel disease patients and is related to disease activity rather than to ASA treatment. Tubular proteinuria seems to reflect a renal extra-intestinal manifestation of inflammatory bowel disease and may serve as a new relevant marker of disease activity.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Background : Azathioprine and mercaptopurine are commonly used in chronic active Crohn's disease. They share the disadvantage of a delayed onset of action and potentially serious side-effects, and are metabolized to thioguanine nucleotides which are thought to be the active metabolites. The direct use of 6-thioguanine may offer a more rapid and safer alternative. We conducted an open prospective study to investigate the efficacy and safety of 6-thioguanine in chronic active Crohn's disease.Methods : Thirty-seven patients with chronic active Crohn's disease and a Crohn's disease activity index of 〉 150 were enrolled in this study. Inclusion criteria were steroid dependence (n = 19), steroid refractoriness (n = 9) and/or intolerance (n = 16) or refractoriness (n = 6) to azathioprine. Patients were treated with 40 mg/day of 6-thioguanine for 24 weeks; a dose escalation to 80 mg was allowed at week 12. Remission was defined as a Crohn's disease activity index of 〈 150 associated with a decrease of 〉 70 points; response was defined as a decrease of 〉 70 points in the Crohn's disease activity index.Results : In the intention-to-treat analysis, 13 of 37 patients achieved remission (35%). Twelve of these 13 patients achieved remission after 4 weeks. Fifty-seven per cent of patients (21/37) achieved a response. The mean Crohn's disease activity index decreased from 284 ± 74 to 153 ± 101. 6-Thioguanine was more effective in azathioprine-intolerant than in azathioprine-refractory patients. Twelve of 16 patients intolerant to azathioprine tolerated 6-thioguanine. Adverse events included phototoxicity, pancreatitis, headache, nausea, alopecia, arthralgia, minor infections and reversible elevation of transaminases. Six patients required discontinuation of medication, two because of leucopenia.Conclusions : In this patient group with chronic active Crohn's disease, 6-thioguanine appeared to be effective with acceptable short-term toxicity, but long-term controlled trials are clearly needed to further define its role.

Electronic Resource

1365-2036

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Background: Tioguanine may offer an alternative for immunosuppression in chronic active Crohn's disease. Recently, we have shown that tioguanine is effective in inducing rapid remission.Aim: To evaluate the role of tioguanine in the maintenance of remission in chronic active Crohn's disease.Methods: A follow-up study was performed to investigate the long-term efficacy and safety of and tolerance to tioguanine in chronic active Crohn's disease. Sixteen patients who had successfully received 6-tioguanine for remission induction were enrolled. The reasons for immunosuppressive therapy were steroid dependence (n = 10), steroid refractoriness (n = 6) and intolerance (n = 6) or refractoriness (n = 1) to azathioprine. After remission induction therapy for 6 months, patients were treated for another 6 months with a daily dose of 20–40 mg tioguanine. Primary outcomes were remission (Crohn's disease activity index 〈 150) and complete steroid reduction in steroid-dependent patients at 12 months. Laboratory controls of white blood count and liver enzymes, as well as erythrocyte tioguanine nucleotide levels, were performed regularly.Results: After 12 months of treatment, 14 of 16 (88%) patients were in remission, and 12 of these were completely free of systemic steroids. Adverse events during maintenance therapy included photosensitivity (one patient), minor viral infections (one), headache (four) and mild alopecia (one). One patient developed elevated liver enzymes, splenomegaly and thrombocytopenia, indicative of nodular regenerative hyperplasia of the liver.Conclusions: In responders to tioguanine, the drug appears to be very effective in maintaining remission of chronic active Crohn's disease. Unfortunately, long-term hepatotoxicity seems to be an unpredictable and potentially severe adverse drug reaction. Therefore, to date, tioguanine cannot be recommended for general use outside clinical trials.

Electronic Resource

1398-9995

Blackwell Publishing Journal Backfiles 1879-2005

Medicine

Electronic Resource

1436-6215

[13C]acetate ; Mass Isotopomer Distribution Analysis ; cholesterol synthesis ; bile ; human subjects ; [13C]Acetat ; Cholesterinsynthese ; Galle ; Mensch

Springer Online Journal Archives 1860-2000

Agriculture, Forestry, Horticulture, Fishery, Domestic Science, Nutrition

Medicine

Zusammenfassung Die Hypersekretion von biliärem Cholesterin scheint der Schlüsseldefekt in der Pathogenese der Cholesteringallensteine zu sein und ist möglicherweise bedingt durch eine erhöhte Cholesterinsynthese. Um die fraktionelle Synthese von biliärem Cholesterin und Plasmacholesterin zu messen, wurden 5 männliche und 3 weibliche gesunde Probanden mit einer intakten enterohepatischen Zirkulation intravenös mit [1-13C]Acetat für 15 h infundiert. Proben duodenaler Galle und Blutproben wurden stündlich gewonnen und eine Formuladiät enteral verabreicht. Die Massenverteilung des freien Cholesterins wurde mittels Gaschromatographie mit Massenspektrometrie analysiert. Die Anwendung der Mass Isotopomer Distribution Analysis — (MIDA) — Technik erlaubte die Berechnung der fraktionellen Synthese. Nach 6stündiger Infusion erreichte die [13C]Markierung des cytosolischen Acetatpools etwa 12%. Die individuellen fraktionellen Cholesterinsynthesen im Plasma und in der Galle korrelierten signifikant miteinander (6–15 h) und betrugen 4,2 und 5,3% nach 15 h. Aus dieser Studie wurde die Schlußfolgerung gezogen, daß neu synthetisiertes Cholesterin gegenüber dem Plasma zu einem höheren Anteil in die Galle sezerniert wird.

Summary Hypersecretion of biliary cholesterol appears to be the key defect in the pathogenesis of cholesterol gallstones, and this may be due to an enhanced synthesis of cholesterol. To measure fractional syntheses of biliary and plasma cholesterol, five male and 3 femalc healthy humans with an intact enterohepatic circulation were infused intravenously with [1-13C]acetate for 15 h. Samples of duodenal bile and blood were taken hourly and an enteral formula diet was given. Free cholesterol mass distribution was analyzed by gas chromatography mass spectrometry. The Mass Isotopomer Distribution Analysis (MIDA) technique allowed to calculate fractional synthesis. After 6 hours of infusion, the [13C]label of the cytosolic acetate pool reached a plateau of approximately 12%. Individual fractional cholesterol synthesis in plasma and bile correlated significantly (6–15 h) and amounted to 4.2% and 5.3% after 15 h, respectively. It may be concluded from this study, that newly synthesized cholesterol is secreted into bile to a higher extent than into plasma.

Electronic Resource

1432-0584

Springer Online Journal Archives 1860-2000

Medicine

Electronic Resource

1432-1289

Springer Online Journal Archives 1860-2000

Medicine

Unter evidenz-basierter Medizin (EBM) versteht man den gewissenhaften, ausdrücklichen und vernünftigen Gebrauch der gegenwärtig besten Evidenz bei ärztlichen Entscheidungen. Wichtig ist hierbei die Integration dieser möglichst objektiven Fakten aus der Literatur mit der klinischen Expertise des einzelnen Arztes. Die evidenz-basierte Medizin hilft beim besseren Verständnis von publizierten Studien zu Diagnostik, Therapie oder Prognose. Allerdings schafft die evidenz-basierte Medizin selbst keine neue Evidenz.

Electronic Resource

1432-1041

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Electronic Resource

1432-1041

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Medicine

Electronic Resource

1573-2568

human ; stomach ; duodenum ; mucosa ; prostaglandin synthesis ; antacids

Springer Online Journal Archives 1860-2000

Medicine

Abstract Using14C-labeled arachidonic acid as precursor for in vitro prostaglandin synthesis, the effect of an antacid containing Al (OH)3, Mg(OH)2 and CaCO3 on endogenous prostaglandin synthesis was investigated in antral and duodenal mucosa of healthy volunteers. After three weeks of treatment with a high-dose antacid, there was no detectable change in the total capacity of the mucosa for prostaglandin synthesis, but the prostaglandin profile was markedly altered. The relative amounts of PGE2 and PGF2α synthesized by antral and duodenal mucosa increased at the expense of the prostaglandinsA2/B2, thromboxane A2, and prostacyclin. In a short-term study, this change was not observed following a single antacid dose within 1 hr after application. It is concluded that long-term antacid treatment may alter the prostaglandin pattern formed by gastroduodenal mucosa and this may be related to its therapeutic effect.

Electronic Resource

1612-1112

Capillary gas chromatography ; Size-exclusion chromatography ; Extraction of serum bile acids

Springer Online Journal Archives 1860-2000

Chemistry and Pharmacology

Summary The profile of serum bile acids is a result of their liver metabolism and enterohepatic circulation. In the present work size exclusion chromatography is used for extraction of serum bile acids to optimize the methodology for analyzing serum bile acids by high resolution gas chromatography. Compared to other extraction methods like adsorption-[1–3] or reversed phase chromatography [4,5], this novel technique yielded a satisfactory recovery (75–104%) with high reproducibility. Therefore a reliable determination of serum bile acids is possible.

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