| 41. |
- Piel, Sarah, et al.
(author)
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Cell-permeable succinate prodrugs rescue mitochondrial respiration in cellular models of acute acetaminophen overdose
- 2020
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:4
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Journal article (peer-reviewed)abstract
- Acetaminophen is one of the most common over-the-counter pain medications used worldwide and is considered safe at therapeutic dose. However, intentional and unintentional overdose accounts for up to 70% of acute liver failure cases in the western world. Extensive research has demonstrated that the induction of oxidative stress and mitochondrial dysfunction are central to the development of acetaminophen-induced liver injury. Despite the insight gained on the mechanism of acetaminophen toxicity, there still is only one clinically approved pharmacological treatment option, N-acetylcysteine. N-acetylcysteine increases the cell's antioxidant defense and protects liver cells from further acetaminophen-induced oxidative damage. Because it primarily protects healthy liver cells rather than rescuing the already injured cells alternative treatment strategies that target the latter cell population are warranted. In this study, we investigated mitochondria as therapeutic target for the development of novel treatment strategies for acetaminophen-induced liver injury. Characterization of the mitochondrial toxicity due to acute acetaminophen overdose in vitro in human cells using detailed respirometric analysis revealed that complex I-linked (NADH-dependent) but not complex II-linked (succinate-dependent) mitochondrial respiration is inhibited by acetaminophen. Treatment with a novel cell-permeable succinate prodrug rescues acetaminophen-induced impaired mitochondrial respiration. This suggests cell-permeable succinate prodrugs as a potential alternative treatment strategy to counteract acetaminophen-induced liver injury.
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| 43. |
- Rutherford, Michael, et al.
(author)
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Randomised clinical trial assessing migration of uncemented primary total hip replacement stems, with and without autologous impaction bone grafting
- 2019
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In: International Orthopaedics. - : Springer. - 0341-2695 .- 1432-5195. ; 43:12, s. 2715-2723
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Journal article (peer-reviewed)abstract
- Purpose: Uncemented stems in primary total hip replacement (THR) are concerning in the elderly due to ectatic femoral canals and cortical thinning resulting in higher incidence of fracture and subsidence in this population. To obviate this concern, the authors developed a technique using autologous impaction bone grafting to achieve a better fitting femoral stem. The aim of this randomised clinical trial was to assess the efficacy of the technique.Methods: From 2013 to 2015, a total of 98 consecutive participants (100 primary THR procedures) were inducted into a single-institution, single-blinded, randomised clinical trial assessing, with radiostereometric analysis (RSA), the efficacy of autologous impaction bone grafting in uncemented primary THR compared with traditional uncemented primary THR technique. The primary outcome measure was femoral component migration using RSA. Secondary outcomes were post-operative proximal femoral bone density (using DEXA), hip function and quality of life using Oxford Hip Score (OHS) and Short Form-12 Health Survey (SF-12), hip pain and patient satisfaction.Results: There was no difference in femoral component stability (p > 0.5) or calcar resorption between the Graft and No Graft Groups at two years. There was also no difference in OHS, SF-12, pain or satisfaction between the Graft and No Graft Groups at two years (p > 0.39).Conclusions: Autologous impaction bone grafting in uncemented primary THR has shown its short-term post-operative outcomes to be equivalent to standard uncemented technique, whilst offering a better fit in patients who are between femoral stem sizes.
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