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- Osto, E., et al.
(författare)
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c-Jun N-terminal kinase 2 deficiency protects against hypercholesterolemia-induced endothelial dysfunction and oxidative stress
- 2008
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Ingår i: Circulation. - 0009-7322. ; 118:20, s. 2073-80
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Tidskriftsartikel (refereegranskat)abstract
- Background— Hypercholesterolemia-induced endothelial dysfunction due to excessive production of reactive oxygen species is a major trigger of atherogenesis. The c-Jun-N-terminal kinases (JNKs) are activated by oxidative stress and play a key role in atherogenesis and inflammation. We investigated whether JNK2 deletion protects from hypercholesterolemia-induced endothelial dysfunction and oxidative stress. Methods and Results— Male JNK2 knockout (JNK2−/−) and wild-type (WT) mice (8 weeks old) were fed either a high-cholesterol diet (HCD; 1.25% total cholesterol) or a normal diet for 14 weeks. Aortic lysates of WT mice fed a HCD showed an increase in JNK phosphorylation compared with WT mice fed a normal diet (P<0.05). Endothelium-dependent relaxations to acetylcholine were impaired in WT HCD mice (P<0.05 versus WT normal diet). In contrast, JNK2−/− HCD mice did not exhibit endothelial dysfunction (96±5% maximal relaxation in response to acetylcholine; P<0.05 versus WT HCD). Endothelium-independent relaxations were identical in all groups. A hypercholesterolemia-induced decrease in nitric oxide (NO) release of endothelial cells was found in WT but not in JNK2−/− mice. In parallel, endothelial NO synthase expression was upregulated only in JNK2−/− HCD animals, whereas the expression of antioxidant defense systems such as extracellular superoxide dismutase and manganese superoxide dismutase was decreased in WT but not in JNK2−/− HCD mice. In contrast to JNK2−/− mice, WT HCD displayed an increase in O2− and ONOO− concentrations as well as nitrotyrosine staining and peroxidation.
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| 2. |
- Aguado, J. M., et al.
(författare)
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Highlighting clinical needs in Clostridium difficile infection : the views of European healthcare professionals at the front line
- 2015
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Ingår i: Journal of Hospital Infection. - : Academic Press. - 0195-6701 .- 1532-2939. ; 90:2, s. 117-125
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Tidskriftsartikel (refereegranskat)abstract
- Background: Clostridium difficile infection (CDI) is the leading cause of infectious nosocomial diarrhoea in Europe. Despite increased focus, its incidence and severity are increasing in many European countries. Aim: We developed a series of consensus statements to identify unmet clinical needs in the recognition and management of CDI. Methods: A consortium of European experts prepared a series of 29 statements representing their collective views on the diagnosis and management of CDI in Europe. The statements were grouped into the following six broad themes: diagnosis; definitions of severity; treatment failure, recurrence and its consequences; infection prevention and control interventions; education and antimicrobial stewardship; and National CDI clinical guidance and policy. These statements were reviewed using questionnaires by 1047 clinicians involved in managing CDI, who indicated their level of agreement with each statement. Findings: Levels of agreement exceeded the 66% threshold for consensus for 27 out of 29 statements (93.1%), indicating strong support. Variance between countries and specialties was analysed and showed strong alignment with the overall consensus scores. Conclusion: Based on the consensus scores of the respondent group, recommendations are suggested for the further development of CDI services in order to reduce transmission and recurrence and to ensure that appropriate diagnosis and treatment strategies are applied across all healthcare settings.
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