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  • 1
    Keywords: RECEPTOR ; EXPRESSION ; Germany ; human ; SYSTEM ; SITE ; GENE ; GENES ; HYBRIDIZATION ; SAMPLE ; PATIENT ; COMPLEX ; BINDING ; BIOLOGY ; MOLECULAR-BIOLOGY ; ASSOCIATION ; DISORDER ; polymorphism ; VARIANTS ; TARGET ; IN-SITU ; ASSAY ; MUTATION ; genetics ; etiology ; REGION ; REGIONS ; REPLICATION ; HEALTHY ; LUCIFERASE ; heredity ; ANTAGONIST ; MANAGEMENT ; molecular biology ; molecular ; DISORDERS ; VARIANT ; NEURONS ; analysis ; EPITHELIUM ; pooled analysis ; HTR3A ; ENGLAND ; MUTATION ANALYSIS ; DYSFUNCTION ; UNTRANSLATED REGION ; POOLED-ANALYSIS ; UK ; 5-HT3 ; ABDOMINAL-PAIN ; ALOSETRON
    Abstract: Diarrhea predominant irritable bowel syndrome (IBS-D) is a complex disorder related to dysfunctions in the serotonergic system. As cis-regulatory variants can play a role in the etiology of complex conditions, we investigated the untranslated regions (UTRs) of the serotonin receptor type 3 subunit genes HTR3A and HTR3E. Mutation analysis was carried out in a pilot sample of 200 IBS patients and 100 healthy controls from the UK. The novel HTR3E 3'-UTR variant c.*76G 〉 A (rs62625044) was associated with female IBS-D (P = 0.033, OR = 8.53). This association was confirmed in a replication study, including 119 IBS-D patients and 195 controls from Germany (P = 0.0046, OR = 4.92). Pooled analysis resulted in a highly significant association of c.*76G 〉 A with female IBS-D (P = 0.0002, OR = 5.39). In a reporter assay, c.*76G 〉 A affected binding of miR-510 to the HTR3E 3'-UTR and caused elevated luciferase expression. HTR3E and miR-510 co-localize in enterocytes of the gut epithelium as shown by in situ hybridization and RT-PCR. This is the first example indicating micro RNA-related expression regulation of a serotonin receptor gene with a cis-regulatory variant affecting this regulation and appearing to be associated with female IBS-D
    Type of Publication: Journal article published
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  • 2
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aim : The gastrointestinal transit of sequentially administered capsules was investigated in relation to the availability of fluid along the intestinal lumen by magnetic resonance imaging.Methods : Water-sensitive magnetic resonance imaging was performed on 12 healthy subjects during fasting and 1 h after a meal. Specifiable non-disintegrating capsules were administered at 7, 4 and 1 h prior to imaging.Results : While food intake reduced the mean fluid volumes in the small intestine (105 ± 72 mL vs. 54 ± 41 mL, P 〈 0.01) it had no significant effect on the mean fluid volumes in the colon (13 ± 12 mL vs. 18 ± 26 mL). The mean number of separated fluid pockets increased in both organs after meal (small intestine: 4 vs. 6, P 〈 0.05; large intestine: 4 vs. 6, P 〈 0.05). The distribution of capsules between the small and large intestine was strongly influenced by food (colon: 3 vs. 17 capsules, P 〈 0.01).Conclusions : The results show that fluid is not homogeneously distributed along the gut, which likely contributes to the individual variability of drug absorption. Furthermore, transport of fluid and solids through the ileocaecal valve is obviously initiated by a meal-induced gastro-ileocaecal reflex.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Gastro-oesophageal reflux disease (GERD) is highly prevalent in Western countries. Because the majority of patients do not present with endoscopic abnormalities, the assessment of the symptom severity and quality of life, and their response to treatment, has become increasingly important. Self-assessed symptom questionnaires are now key instruments in clinicaltrials.Aim : To evaluate the validity of available GERD measurement tools.Methods : An ideal GERD symptom assessment instrument, suitable as a primary end-point for clinical trials, should possess the following characteristics: (i) be sensitive in patients with GERD; (ii) cover the frequency and intensity of typical and atypical GERD symptoms; (iii) be multidimensional (cover all symptom dimensions); (iv) have proven psychometric properties (validity, reliability and responsiveness); (v) be practical and economical; (vi) be self-assessed; (vii) use ‘word pictures’ which are easy to understand for patients; (viii) respond rapidly to changes (responsiveness over short time intervals); (ix) be used daily to assess changes during and after therapy; and (x) be valid in different languages for international use.Results : A literature review revealed five scales that met some of the above characteristics, but did not fulfil all criteria.Conclusion : There is a need for a new evaluative tool for the assessment of GERD symptoms and their response to therapy.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1433-8580
    Keywords: Catecholamines ; Gastrin ; Man ; Pancreatic polypeptide ; Physical exercise
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The influence of circulating catecholamines on the release of pancreatic polypeptide (PP) and gastrin was studied in volunteers. Physical exercise increased plasma epinephrine by 374 ± 123% and plasma norepinephrine by 167 ± 30%, but plasma PP concentrations remained unchanged during standardized bicycle ergometry. Immediately after cessation of exercise catecholamine levels decreased rapidly, whereas PP concentrations increased by 55%. In a second series, epinephrine infusion (5, 25, and 75 ng · kg−1 · min−1) increased epinephrine levels by 38 ± 12, 331 ± 69, and 1229 ± 131%, respectively, whilst norepinephrine was unaffected. Neither during nor after catecholamine infusion PP secretion was affected. Gastrin release increased by a maximum of 85 ± 38% (at epinephrine 75 ng · kg−1 · min−1). It is concluded, that (1) changes in circulating adrenaline do not significantly influence PP secretion in man; (2) the PP increase immediately following physical exercise cannot be attributed to a rapid fall of catecholamine levels; (3) endogenous catecholamines are of minor importance in the control of gastrin secretion.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1365-2036
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Background : Reflux Questionnaire (ReQuest), a newly developed gastro-oesophageal reflux disease-sensitive scale, can be used to reliably evaluate the effect of treatment on gastro-oesophageal reflux disease symptoms.Aim : International validation of this scale, in patients suffering from endoscopy-negative gastro-oesophageal reflux disease.Methods : In this open, multicentre and multinational clinical trial 840 endoscopy-negative gastro-oesophageal reflux disease patients received pantoprazole 20 mg daily for 28 days. The long and short versions of ReQuest were completed both in the pre-treatment and treatment phases. For scale development an item reduction analysis was performed. Internal consistency, test–retest reliability and responsiveness were calculated for psychometric analysis. Construct validity was evaluated by comparison with the Gastrointestinal Symptom Rating Scale and the Psychological General Well-being questionnaire by means of correlation coefficients.Results : Factor analyses confirmed the content validity of both long and short version of ReQuest. Psychometric calculations proved high internal consistency (Cronbach's alpha: 0.9), test–retest reliability [Intraclass Correlation Coefficient: 0.9 (long vs. long) and 0.8 (short vs. short)], and responsiveness (Responsiveness Index 320.3) of the scale, for which also good construct validity was achieved (correlation coefficient: Gastrointestinal Symptom Rating Scale –0.6; Psychological General Well-being −0.4).Conclusion : ReQuest proved valid, reliable, and responsive in this multinational clinical trial to evaluate treatment response in endoscopy-negative gastro-oesophageal reflux disease patients.
    Type of Medium: Electronic Resource
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