Metabolism of deltamethrin and cis- and trans-permethrin by human expressed cytochrome P450 and carboxylesterase enzymes

1. The metabolism of the pyrethroids deltamethrin (DLM), cis-permethrin (CPM) and trans-permethrin (TPM) was studied in human expressed cytochrome P450 (CYP) and carboxylesterase (CES) enzymes.

2. DLM, CPM and TPM were metabolised by human CYP2B6 and CYP2C19, with the highest apparent intrinsic clearance (CL_int) values for pyrethroid metabolism being observed with CYP2C19. Other CYP enzymes contributing to the metabolism of one or more of the three pyrethroids were CYP1A2, CYP2C8, CYP2C9*1, CYP2D6*1, CYP3A4 and CYP3A5. None of the pyrethroids were metabolised by CYP2A6, CYP2E1, CYP3A7 or CYP4A11.

3. DLM, CPM and TPM were metabolised by both human CES1 and CES2 enzymes.

4. Apparent CL_int values for pyrethroid metabolism by CYP and CES enzymes were scaled to per gram of adult human liver using abundance values for microsomal CYP enzymes and for CES enzymes in liver microsomes and cytosol. TPM had the highest and CPM the lowest apparent CL_int values for total metabolism (CYP and CES enzymes) per gram of adult human liver.

5. Due to their higher abundance, all three pyrethroids were extensively metabolised by CES enzymes in adult human liver, with CYP enzymes only accounting for 2%, 10% and 1% of total metabolism for DLM, CPM and TPM, respectively.

     

Patients Are Knowledge Workers in the Clinical Information Space

Background  Limited research exists on patient knowledge/cognition or “getting inside patients'' heads.” Because patients possess unique and privileged knowledge, clinicians need this information to make patient-centered and coordinated treatment planning decisions. To achieve patient-centered care, we characterize patient knowledge and contributions to the clinical information space. Methods and Objectives  In a theoretical overview, we explore the relevance of patient knowledge to care provision, apply historical perspectives of knowledge acquisition to patient knowledge, propose a representation of patient knowledge types across the continuum of care, and include illustrative vignettes about Mr. Jones. We highlight how the field of human factors (a core competency of health informatics) provides a perspective and methods for eliciting and characterizing patient knowledge. Conclusion  Patients play a vital role in the clinical information space by possessing and sharing unique knowledge relevant to the clinical picture. Without a patient''s contributions, the clinical picture of the patient is incomplete. A human factors perspective informs patient-centered care and health information technology solutions to support clinical information sharing.     

Denial of Human Rights: We Must Change the Paradigm of Dementia Care

In far too many instances treatment of persons with dementia has reflected a fundamental denial of basic human rights. At times, these individuals are treated worse than the treatment of animals when the five basic freedoms of animals, described by Pachana in her editorial, are implemented. A number of such examples of dehumanizing (and “de-animalizing”) persons with dementia are presented. A case is made for the position that this is the direct result of the “medicalization” of dementia and “Alzheimer Disease.” This has led to the disenfranchisement of persons with dementia and their caregivers regarding the treatment of dementia, while medical “expertise” has led to a paradigm of learned helplessness while waiting for “the cure.” While the medicalization of dementia has been a financial success in terms of funding failed researcher to find a cure, it has been a catastrophe for the quality of life of persons with dementia and their caregivers. It is time to take control of the treatment of dementia back, and especially to listen to the voices of persons with dementia. It is time to take action NOW – to become disruptive to the current paradigm. The emperor and his cure have no clothes. We deserve better. We must make this change in paradigm our mission, to demand it, and to accept nothing less. Power to the people.     

颈前入路相关结构三维可视化研究

目的：建立颈前入路相关结构的三维可视化模型。方法：选取首例中国数字化可视人体数据集中第3颈椎上缘至第7颈椎下缘的连续薄层断面图像。运用3D—DOCTOR软件，在计算机上分割重建该手术入路相关的解剖结构并立体显示。结果：成功重建并立体显示第3～7颈椎、椎间盘、脊髓、颈神经、椎动脉、颈长肌、喉（气管）、咽（食管）、颈总动脉（颈内、外动脉）、颈内静脉、迷走神经和胸锁乳突肌等解剖结构的位置关系，建立了颈前入路相关结构的三维可视化模型。结论：在颈部三维可视化模型基础上，参照颈前入路手术步骤可逐层显示该手术相关的重要结构．为该手术的术前训练和模拟提供形态学依据。     

携载rhBMP-2微球的新型可注射自凝固复合人工骨的制备及特性研究

[目的]制备一种具有良好降解性和成骨活性、可注射的自凝固新型骨修复材料。[方法]制备携载rhBMP-2的聚乳酸与聚乙醇酸共聚物（PLGA）微球，并将其与rhBMP-2／磷酸钙骨水泥（CPC）复合，制备出rhBMP-2／PLGA微球／CPC复合人工骨。探讨了材料的特性，包括形貌、固化时间、抗压强度及反映材料体外降解速度的指标一体外降解液Ca、P浓度变化，测定复合材料rhBMP乏的释药速度及体外诱导MSCs细胞成骨分化的能力。[结果]与单纯CPC-rhBMP-2相比，复合材料的固化时间少量增加，抗压强度下降明显。体外降解速度及体外释药明显提高，释放的rhBMP-2具有骨诱导活性。[结论]rhBMP-2／PLGA微球／磷酸钙骨水泥新型复合人工骨是具有良好应用前景的骨修复材料。     

Ex vivo identification of atherosclerotic plaque calcification by a 31P solid-state magnetic resonance imaging technique.

Calcified tissue is a common component of atherosclerotic plaques, and occurs most often in mature plaques. The process of calcification is a poorly understood risk factor that may contribute to a plaque's vulnerability to sudden rupture. In this study a solid-state imaging sequence, termed single-point imaging (SPI), was used to observe calcification directly in ex vivo atherosclerotic plaques. Standards were used to validate the ability of (31)P SPI to detect and differentiate calcification from crystalline cholesterol, phospholipids, and other plaque components. After suitable experimental parameters were found, human carotid specimens obtained by endarterectomy were imaged ex vivo by (31)P solid-state imaging and standard (1)H methods. In contrast to (1)H imaging methods, (31)P imaging detected only the calcification in the plaque.     

早期联用MEP和大剂量rhGH对严重烫伤大鼠肠源性感染的影响

目的探讨早期联用美罗培南(MEP)和大剂量重组人生长激素(rhGH)对严重烫伤免疫抑制大鼠肠源性感染的影响。方法Wistar大鼠54只随机分为对照组、烧伤组和治疗组(C1组、C2组、C3组),后两大组制成25%总体表面积(TBSA)Ⅲ°烫伤免疫抑制模型,伤后2h给予rhGH1.33IU/kg、MEP20mg/kg,伤后8、24h检测门静脉血清内毒素(LPS)、腔静脉血清肿瘤坏死因子-α(TNF-α)含量,肝功能变化和肠道细菌移位率。结果C3(MEP+rhGH治疗)组LPS和TNF-α含量均显著低于其他组(P<0.01),与对照组差异无统计学意义(P>0.05),C3组未发现肠道细菌移位且肝功能检测指标显著低于其他组(P<0.01),与对照组差异无统计学意义(P>0.05)。结论早期联用MEP和rhGH治疗严重烫伤免疫抑制大鼠能显著减轻或防止肠道细菌/内毒素移位,减少炎症介质释放,保护脏器功能。