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  • 1
    Abstract: BACKGROUND: Statins (HMG CoA reductase inhibitors), in addition to reducing circulating cholesterol and incidence of coronary heart disease, also have pleiotropic, anti-inflammatory effects. Patients with chronic liver diseases, non-alcoholic fatty liver disease (NAFLD) or hepatitis C are often excluded from statin therapy because of adverse effects in a small cohort of patients despite increased cardiovascular risk cholesterol. Ezetimibe, which inhibits cholesterol absorption by inhibition of Niemann-Pick C1 like 1 (NPC1L1) protein in the brush border of intestinal cells, has been suggested as a new therapeutic option in these patients. METHODS: Effects of ezetimibe on lipoprotein metabolism, hepatic and intestinal lipid content in guinea pigs, an animal model with a lipoprotein profile and pattern similar to humans were investigated. In order to investigate a possible effect of ezetimibe on cholesterol induced inflammation NF-kappaB activation as an indicator for inflammatory processes in liver and gut tissue was measured. RESULTS: Lipid enriched diet led to accumulation of lipids in hepatic tissue which caused strong hepatic NF-kappaB activation. Ezetimibe reduced lipid diet induced increase of circulating cholesterol by about 77% and prevent hepatic NF-kappaB activation almost completely. In contrast in intestinal cells Ezetimibe, though lowering diet induced cholesterol accumulation, increased triglyceride content and subsequent NF-kappaB activation. CONCLUSION: In summary these data show, that ezetimibe effectively reduced diet induced circulating cholesterol levels, hepatic lipid accumulation and inflammatory response in our guinea pig model. However this drug elicited a local inflammatory response in intestinal tissue. Whether these diverse effects of ezetimibe on inflammatory parameters such as NF-kappaB have clinical relevance remains to be determined.
    Type of Publication: Journal article published
    PubMed ID: 28167864
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  • 2
    Keywords: ACTIVATION, ADJUVANT, ADJUVANT THERAPY, BACTEREMIA, CARE, CELLS, cholesterol, COENZYME-A REDUCTASE,
    Abstract: Statins, which are effective lipid-lowering drugs, also possess anti-inflammatory potential. However, circulating lipoproteins may also play a protective role during acute inflammatory diseases because of their ability to bind bacterial toxins. Low cholesterol levels have been reported in inflammatory conditions, and plasma cholesterol concentrations inversely correlate with severity and clinical outcome in septic patients. It is thus paradoxical that statins, which drastically reduce circulating cholesterol levels, should be beneficial in patients with inflammatory disease who are already hypocholesterolemic. We investigated the effect of simvastatin on LPS-induced nuclear factor kappa B (NF-kappa B) activation, TNF release, and mortality in guinea pigs, an animal model with a lipoprotein profile and pattern similar to humans. In the present study, simvastatin reduced circulating total and low-density lipoprotein cholesterol levels by 68% and 76%, respectively, and LPS-induced mortality from 73% to 20%. This reduction was accompanied by a significant reduction of NF-kappa B activation in the liver tissue, splenocytes, and plasma TNF levels by about 80%, 50%, and 77%, respectively. Our data suggest that simvastatin, despite lowering circulating low-density lipoprotein cholesterol, decreased LPS toxicity by reduction of NF-kappa B activation and subsequent release of TNF by modulating 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and therefore deserves consideration as a possible adjuvant therapy in acute inflammatory disease
    Type of Publication: Journal article published
    PubMed ID: 19008785
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  • 3
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    German Medical Science; Düsseldorf, Köln
    In:  123. Kongress der Deutschen Gesellschaft für Chirurgie; 20060502-20060505; Berlin; DOC06dgch5739 /20060502/
    Publication Date: 2006-05-09
    Keywords: ddc: 610
    Language: German
    Type: conferenceObject
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  • 4
    ISSN: 1432-1238
    Keywords: Key words Procalcitonin ; Acute rejection ; Heart transplantation ; Lung transplantation ; Infection
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: Investigation of the reliability of Procalcitonin (PCT) for differential diagnosis of acute rejections and non-viral infections in heart and lung transplanted patients.¶Design: Retrospective study.¶Setting: Transplant intensive care unit (ICU) at a university hospital.¶Patients: 57 heart, 18 lung and 3 heart-lung transplant patients.¶Measurements: PCT was measured in plasma samples of heart and lung transplanted patients using a commercial immuno-luminescence assay and was compared with values of C-reactive protein (CRP) and leukocytes (WBC).¶Results: PCT was elevated in patients suffering from bacterial and fungal infections. The magnitude of values was clearly associated with the severity of the infection. Rejections and viral infections did not interfere with the PCT release.¶Conclusion: PCT is a reliable predictor with discriminating power for non-viral systemic infections in patients after heart and/or lung transplantation. PCT allows an early differential diagnosis between rejection (AR) and bacterial/fungal infection (IF) and thus a rapid and focused therapeutic intervention. It avoids unnecessary antibiotic treatment which could be toxic for the graft itself in patients with rejection only. PCT provides vital information early to clinicians and allows them to improve the management of bacterial/fungal infections in immunocompromized transplant patients. PCT thus facilitates and improves the outcome of survival rate and the quality of life in the postoperative period of patients with heart and/or lung grafts.
    Type of Medium: Electronic Resource
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