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  • 1
    In: Digestion, S. Karger AG, Vol. 84, No. 2 ( 2011), p. 156-167
    Abstract: 〈 i 〉 Background/Aims: 〈 /i 〉 The non-lysosomal glucosylceramidase, β-glucosidase (Gba2), hydrolyzes glucosylceramide to glucose and ceramide (Cer). Cer is a potent second-messenger lipid that plays an important role in signaling cascades involved in apoptosis. The aim of this study was to investigate whether Gba2 knock-out (Gba2 〈 sup 〉 –/– 〈 /sup 〉 ) affects the extent of dextran sulfate sodium (DSS)-induced colitis in mice. 〈 i 〉 Methods: 〈 /i 〉 Acute colitis was induced in wild-type (WT) and Gba2 〈 sup 〉 –/– 〈 /sup 〉 mice by administration of 2% DSS in drinking water. After 7 days, mice underwent colonoscopy and were sacrificed. 〈 i 〉 Results: 〈 /i 〉 Both DSS-treated WT (n = 10) and Gba2 〈 sup 〉 –/– 〈 /sup 〉 (n = 12) mice showed elevated histological and endoscopic scores compared to respective H 〈 sub 〉 2 〈 /sub 〉 O controls (n = 9 each). However, no significant differences between the DSS groups were detected. Flow cytometric analysis of propidium iodide staining, cleavage of caspases-3 and -8, indicative for apoptosis, as well as Cer levels were not altered in DSS-treated WT or Gba2 〈 sup 〉 –/– 〈 /sup 〉 mice. Gba2 〈 sup 〉 –/– 〈 /sup 〉 resulted in slightly decreased expression of glucocerebrosidase (Gba1) as well as in upregulation of proteins being involved in cellular regeneration, such as STAT3 (signal transducer and activator of transcription), JNK and iNOS, upon DSS treatment. 〈 i 〉 Conclusion: 〈 /i 〉 We demonstrate that Gba2 〈 sup 〉 –/– 〈 /sup 〉 does not affect the extent of DSS-induced inflammation in mice, however, it might be involved in tissue regeneration in response to toxic agents.
    Type of Medium: Online Resource
    ISSN: 0012-2823 , 1421-9867
    RVK:
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2011
    detail.hit.zdb_id: 1482218-0
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  • 2
    In: Cardiology, S. Karger AG, Vol. 97, No. 1 ( 2002), p. 29-36
    Abstract: 〈 i 〉 Background: 〈 /i 〉 Experimental studies have shown an activation of the angiotensin-converting enzyme (ACE) system as a response to endothelial injury. Recent publications have elucidated the hypothesis that the ACE gene polymorphism may influence the level of late luminal loss after coronary stent implantation. It is still unclear whether the polymorphism of the angiotensin gene is a major predictor of the extent of neointimal hyperplasia. In this multicenter study, we therefore tested the relationship between the ACE gene polymorphism and the restenosis rate after coronary stent implantation. 〈 i 〉 Methods: 〈 /i 〉 As a substudy of the optimization with intracoronary ultrasound (ICUS) to reduce stent restenosis (OPTICUS) study, we analyzed ACE serum levels and the ACE gene polymorphism in 154 patients at 9 different centers. All patients underwent elective coronary stent implantation in a stenosis of a major coronary vessel. Balloon inflations were repeated until a satisfactory result was achieved in on-line quantitative coronary angiography or ICUS fulfilling the OPTICUS study criteria. After follow-up of 6 months, all patients underwent reangiography under identical projections as the baseline procedure. A blinded quantitative analysis of the initial procedure as well as the follow-up examinations were performed by an independent core laboratory. ACE gene polymorphism and ACE serum activity were measured at the 6-month follow-up in a double-blinded setting. 〈 i 〉 Results: 〈 /i 〉 With respect to the ACE gene polymorphism, there were three subgroups: DD genotype (48 patients), ID (83 patients) and II (23 patients). The subgroups did not differ in regard to age, gender, extent of coronary artery disease, stenosis length, initial degree of stenosis or degree of stenosis after stent implantation. In all, 39 patients (25.3%) had significant restenosis: 12 DD patients (25.0%), 18 ID patients (21.7%) and 9 II patients (39.1%) (odds ratio 2.164, 95% confidence interval 0.853–5.493). We obtained the following results for ACE serum levels: 0.53 µmol/l/s in the DD subgroup, 0.29 µmol/l/s in the ID subgroup and 0.09 µmol/l/s in the II subgroup (p 〈 0.001). Multivariate logistic regression analysis of the influence of ACE gene polymorphism on the restenosis rate after coronary stent implantation adjusted for lesion length ( 〉 12 mm), ACE inhibitor or hydroxymethylglutaryl coenzyme A reductase (CSE) inhibitor treatment, age, male gender, diabetes mellitus, hypertension, high cholesterol, family history, smoking and three-vessel disease did not uncover any statistic significance. 〈 i 〉 Conclusions: 〈 /i 〉 In contrast to other study groups, we were unable to disclose that the DD polymorphism of the ACE gene was associated with a higher rate of restenosis after coronary stent implantation in this multicenter study. In addition, patients with higher ACE serum levels did not show a higher restenosis rate in this trial. We conclude that the pathogenesis of restenosis is a multifactorial process involving various genetic and nongenetic factors.
    Type of Medium: Online Resource
    ISSN: 0008-6312 , 1421-9751
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2002
    detail.hit.zdb_id: 1482041-9
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