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101.
Rohi Shah Nomaan Sheikh Jitendra Mangwani Nicolette Morgan Hamidreza Khairandish 《Journal of Clinical Orthopaedics and Trauma》2021,12(1):138
Demographic projections for hip fragility fractures indicate a rising annual incidence by virtue of a multimorbid, ageing population with more noncommunicable diseases (NCDs). NCDs are characterised by slow progression and long duration ranging from ischaemic cardiovascular disease, cerebrovascular disease, diabetes, chronic obstructive pulmonary disease to various cancers. Management of this disease burden often involves commencing patients on oral anticoagulants to reduce the risk of thromboembolic events. The use of direct oral anticoagulants (DOACs) in clinical practice has increased due to their rapid onset of action, short half-life and predictable anticoagulant effects, without the need for routine monitoring. Safe and timely surgical intervention relies on reversal of anticoagulants. However, the lack of specific evidence-based guidelines for the perioperative management of patients on DOACs with hip fractures has proved challenging; in particular, the accessibility of DOAC-specific assays, justification of the cost-benefit ratio of targeted reversal agents and indications for neuraxial anaesthesia. This has led to potentially avoidable delays in surgical intervention. Following a literature review of the pharmacokinetic and pharmacodynamics of commonly used DOACs in our region including the role of surrogate markers, we propose a systematic, evidence-based guideline to the perioperative management of hip fractures DOACs. We believe this standardised protocol can be easily replicated between hospitals. We recommend that if patients are deemed suitable for a general anaesthesia, with satisfactory renal function, optimal surgical time should be 24 h following the last ingested dose of DOAC. 相似文献
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ABSTRACTThis work collates data from the analysis of complex mixtures analysed in STRmix during routine no-suspect volume crime work. It interrogates the upload rate for these types of mixtures and which component of the profile has been able to be interpreted for upload. The number of profiles giving multiple uploads and the amount of replicate PCR analysis has been collated. 相似文献
104.
目的 通过观察早产儿不同胎龄Toll样受体9(TLR9)的表达,探讨早产儿免疫功能低下的机制。方法 采集2010年7月至2014年6月在上海市嘉定区妇幼保健院产科出生的活产新生儿的脐血229份,按胎龄分为4组,28~31周组,31~34周组,34~37周组,≥37周组,采用流式细胞术和实时荧光定量PCR方法,分别检测其TLR9的蛋白和mRNA表达情况,了解其与胎龄之间的关系,并分析mRNA和蛋白表达间的相关性。结果 TLR9阳性细胞率在28~31周组,31~34周组,34~37周组,≥37周组分别为(15.93±6.23)%,(11.63±6.70)%,(13.66±6.88)%,(20.51±12.06)%;其在胎龄28~31周较高,至31~34周逐渐下降至最低,两组差异有统计学意义(P<0.05);34~37周后TLR9阳性细胞率表达逐渐升高,至≥37周达最高,两胎龄组比较,差异具有统计学意义(P<0.05)。31~37周间新生儿脐血TLR9阳性细胞率与胎龄呈正相关(r=0.273,P=0.006)。TLR9 mRNA表达在28~31周组,31~34周组,34~37周组,≥37周组分别为(4.95±3.44)%,(8.89±8.49)%,(13.91±10.92)%,(7.19±7.11)%;其在28~36周逐渐升高,与胎龄呈正相关(r=0.355,P< 0.001)。≥37周TLR9 mRNA表达量下降,该值虽高于28~31周,但差异无统计学意义(P>0.05)。相关性分析表明,同胎龄时期同样本新生儿的TLR9 mRNA和TLR9阳性细胞率之间存在负相关(r=-0.227,P=0.011)。结论 TLR9阳性细胞率和TLR9 mRNA表达在不同胎龄组新生儿间有差异,TLR9阳性细胞率表达在31~37周间随着胎龄的增加而增加,TLR9 mRNA在28~36周间随着胎龄的增加而增加。 相似文献
105.
《Drug metabolism and pharmacokinetics》2020,35(1):56-70
Hepatic uptake mediated by organic anion transporting polypeptide (OATP) 1B1 and 1B3 can serve as a major elimination pathway for various anionic drugs and as a site of drug-drug interactions (DDIs). This article provides an overview of the in vitro approaches used to predict human hepatic clearance (CLh) and the risk of DDIs involving OATP1Bs. On the basis of the so-called extended clearance concept, in vitro–in vivo extrapolation methods using human hepatocytes as in vitro systems have been used to predict the CLh involving OATP1B-mediated hepatic uptake. CLh can be quantitatively predicted using human donor lots possessing adequate OATP1B activities. The contribution of OATP1Bs to hepatic uptake can be estimated by the relative activity factor, the relative expression factor, or selective inhibitor approaches, which offer generally consistent outcomes. In OATP1B1 inhibition assays, substantial substrate dependency was observed. The time-dependent inhibition of OATP1B1 was also noted and may be a mechanism underlying the in vitro–in vivo differences in the inhibition constant of cyclosporine A. Although it is still challenging to quantitatively predict CLh and DDIs involving OATP1Bs from only preclinical data, understanding the utility and limitation of the current in vitro methods will pave the way for better prediction. 相似文献
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109.
Rosario Gulias-Cañizo Anell Lagunes-Guillén Arturo González-Robles Erika Sánchez-Guzmán Federico Castro-Muñozledo 《Burns : journal of the International Society for Burn Injuries》2019,45(2):398-412
Background
Since recent reports have shown that (-)-Epigallocatechin-3-gallate (EGCG) could be used for treating proliferative and inflammatory disorders, we explored its use for the management of corneal chemical burns.Materials and methods
Initially, EGCG was assayed on the rabbit corneal epithelial cell line RCE1(5T5) to establish the best testing conditions, and to avoid unwanted outcomes in the experimental animals. Then, we studied its effects on cell proliferation, cell cycle progression and cell differentiation. Afterwards, we instilled EGCG in experimental grade II corneal alkali burns in mice, three times a day up to 21 days, and evaluated by slit lamp examination and histological sections of corneal epithelial, corneal endothelial and stromal edema, as well as the presence of inflammatory cells and neovascularization.Results
EGCG reduced cell growth and led to a decline in the proportion of proliferative cells in a concentration dependent manner. At 10 μM, EGCG promoted cell differentiation, an effect not related with apoptosis or cytotoxicity. When 10 μM EGCG was instilled in corneal alkali burns in mice three times a day up to 21 days, EGCG significantly reduced corneal opacity and neovascularization. The improved clinical appearance of the cornea was associated to a controlled epithelial growth; epithelial morphology was similar to that observed in normal epithelium and contrasted with the hyperproliferative, desquamating epithelium observed in control burn wounds. EGCG reduced corneal, stromal and endothelial edema, and wound inflammation.Conclusion
This work constitutes the first evidence for the use of EGCG in the acute phase of a corneal alkali burn, representing a possible novel alternative to improve patient outcomes as an add-on therapy. 相似文献110.
2型糖尿病及骨质疏松已成为我国最主要的慢性代谢性疾病。2型糖尿病常伴有血脂紊乱,常表现为低密度脂蛋白升高,而越来越多的研究表明血脂通过不同的方式影响骨代谢,其机制可能是通过抑制骨髓间充质干细胞成骨分化,通过RANK/RNAKL/OPG信号通路及炎症反应调节破骨细胞等方式调节骨代谢。 相似文献