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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 3. |
- Lassen, Michael R, et al.
(författare)
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Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty
- 2008
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Ingår i: The New England journal of medicine. - 0028-4793. ; 358:26, s. 86-2776
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We investigated the efficacy of rivaroxaban, an orally active direct factor Xa inhibitor, in preventing venous thrombosis after total knee arthroplasty.METHODS: In this randomized, double-blind trial, 2531 patients who were to undergo total knee arthroplasty received either oral rivaroxaban, 10 mg once daily, beginning 6 to 8 hours after surgery, or subcutaneous enoxaparin, 40 mg once daily, beginning 12 hours before surgery. The primary efficacy outcome was the composite of any deep-vein thrombosis, nonfatal pulmonary embolism, or death from any cause within 13 to 17 days after surgery. Secondary efficacy outcomes included major venous thromboembolism (i.e., proximal deep-vein thrombosis, nonfatal pulmonary embolism, or death related to venous thromboembolism) and symptomatic venous thromboembolism. The primary safety outcome was major bleeding.RESULTS: The primary efficacy outcome occurred in 79 of 824 patients (9.6%) who received rivaroxaban and in 166 of 878 (18.9%) who received enoxaparin (absolute risk reduction, 9.2%; 95% confidence interval [CI], 5.9 to 12.4; P<0.001). Major venous thromboembolism occurred in 9 of 908 patients (1.0%) given rivaroxaban and 24 of 925 (2.6%) given enoxaparin (absolute risk reduction, 1.6%; 95% CI, 0.4 to 2.8; P=0.01). Symptomatic events occurred less frequently with rivaroxaban than with enoxaparin (P=0.005). Major bleeding occurred in 0.6% of patients in the rivaroxaban group and 0.5% of patients in the enoxaparin group. The incidence of drug-related adverse events, mainly gastrointestinal, was 12.0% in the rivaroxaban group and 13.0% in the enoxaparin group.CONCLUSIONS: Rivaroxaban was superior to enoxaparin for thromboprophylaxis after total knee arthroplasty, with similar rates of bleeding. (ClinicalTrials.gov number, NCT00361894.)
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