基于药效理化表征的当归补血汤质量控制模式初探

目的 研究当归补血汤不同体系与其理化参数的关系,探讨利用药效理化参数来表征中药汤剂质量的可行性。方法 以水为分散介质,参照不同分散体系的研究方法,对黄芪甲苷、阿魏酸、黄芪皂苷、黄芪多糖等当归补血汤的代表性组分及当归补血汤单味药、复方提取液的理化特征进行表征,建立包括表面特性、电性质、流变性、热力学等性质的表征方法,并进行参数与处理因素的多项式回归分析。结果 随着阿魏酸质量浓度增大,阿魏酸水溶液、当归水提液、复方水提液的pH值降低、电导率增大;随着黄芪甲苷与黄芪皂苷质量浓度的增大,黄芪甲苷水溶液、黄芪皂苷水溶液、黄芪水提液、复方水提液的表面张力降低;随着多糖质量浓度的增大,复方水提液的渗透压增大。在整个当归补血汤体系中影响pH值和电导率的主导成分是阿魏酸,影响表面张力的主导组分是黄芪皂苷,影响渗透压的主导组分为多糖,且不同工艺制备的汤剂的理化参数大小趋势与药效强弱也有较强的相关性。结论 初步表明表面张力、pH值、电导率、渗透压4个参数能反映当归补血汤的内在质量,在一定程度上可以作为当归补血汤制备工艺与汤剂质量控制的参考指标。     

The evolution of lung transplantation for cystic fibrosis: A 2017 update

Lung transplantation (LTx) is an established therapy for patients with end-stage cystic fibrosis (CF). Indeed, CF is the commonest indication for those aged < 50 years of age needing LTx. CF LTx is associated with a 45% 10 year survival - according to the world's largest registry. It is important all otherwise suitable CF patients with severe lung disease have a timely referral for discussion and consideration of the possibility of LTx. LTx discussions must carefully consider colonisation or infection with Burkholderia cenocepacia, Mycobacterium abscessus and Scediosporium - as good LTx outcomes cannot be guaranteed. A bridge to LTx with extra-corporeal lung support is a realistic option, but remains a relative contraindication to LTx. Improvements in LTx matching technology and post-operative management are steadily improving overall long-term outcomes, although chronic allograft rejection remains problematic. Expert multidisciplinary life-long post-LTx care remains the key to success.     

Making a national donor research program a reality: Concepts for operationalizing a system

Deceased donor research remains an elusive goal for improving organ utilization and function. Many working in this field have cited the barriers that impede the conduct of such trials. Recent reports from the Academy of Medicine and individual authors provide a general framework on which a National Donor Research Program could be built. This paper provides one observer's viewpoint on how such a program could be operationalized.     

Organ donor management and delayed graft function in kidney transplant recipients: A multicenter retrospective cohort study

Meeting donor management goals (DMGs) has been reported to decrease the incidence of delayed graft function (DGF) after kidney transplant, but whether this relationship is independent of cold machine perfusion is unclear. We aimed to determine whether meeting DMGs is associated with a reduced incidence of DGF, independent of the use of machine perfusion. We collected data on consecutive brain‐dead donors and their KT recipients (KTRs) between June 2013 and December 2016 in 5 adult transplant centers. We evaluated whether DMGs were met at donor neurologic death (DND) and later time points. We defined a priori meeting optimal DMG as achieving ≥7 DMGs. Generalized estimating equations were used to predict DGF. Among 122 donors, 34% were extended‐criteria donors (ECDs). The number of DMGs met increased over time (5.6 ± 1.4 at DND and 6.1 ± 1.3 at organ procurement [P < .001]). DGF occurred in 23% of 214 KTRs, and 55% received organs placed on machine perfusion. In multivariate analysis, ECD (odds ratio [OR] 2.24, 95% confidence interval [CI] 1.13‐4.45), use of machine perfusion (OR 0.45, 95% CI 0.22‐0.94), and optimal DMG at DND (OR 0.39, 95% CI 0.16‐0.99) were associated with DGF. Early achievement of DMGs was associated with a reduced risk of the development of DGF, independent of the use of machine perfusion.     

Polycyclic aromatic hydrocarbons stimulate human CYP3A4 promoter activity via PXR

Metabolic activation of polycyclic aromatic hydrocarbons (PAH) is mediated mainly by cytochrome P₄₅₀ monooxygenases (CYP) CYP1A1, 1A2 and 1B1. Several PAH are known to induce these CYP via aryl hydrocarbon receptor (AhR) signaling. Recently, it was shown that the PAH benzo[a]pyrene (BaP) can induce CYP3A4 as well. The induction was suggested to be mediated by the pregnane X receptor (PXR) rather than AhR. Metabolism by CYP3A4 is only known for dihydrodiol metabolites of PAH but not for their parent compounds.     

Therapeutic options for recurrent malignant glioma

Background and purpose: Despite the given advances in neuro-oncology most patients with high grade malignant glioma ultimately fail locally or locoregionally. In parallel with improvements of initial treatment options, several salvage strategies have been elucidated and already entered clinical practice. Aim of this article is to review the current status of salvage strategies in recurrent high grade glioma. Material and methods: Using the following MESH headings and combinations of these terms the pubmed database was searched: “Glioma”, “Recurrence”, “Neoplasm Recurrence, Local”, “Radiosurgery”, “Brachytherapy”, “Neurosurgical Procedures” and “Drug Therapy”. For citation crosscheck the ISI web of science database was used employing the same search terms. In parallel, the abstracts of ASCO 2008-2009 were analyzed accordingly. Results: Currently the following options for salvage entered clinical practice: re-resection, re-irradiation (stereotactic radiosurgery, (hypo-)fractionated (stereotactic) radiotherapy, interstitial brachytherapy) or single/poly-chemotherapy schedules including new dose-intensified or alternative treatment protocols employing targeted drugs. Re-operation is associated with high morbidity and mortality, however, is an option in a highly selected patient cohort. Since toxicity has been overestimated, re-irradiation is an increasingly used option with precise fractionated radiotherapy being the most optimal technique. On average, time to secondary progression is in the range of several months. Conventional chemotherapy regimens also improve time to secondary progression; however the efficacy is only modest and treatment-related toxicities like myelo-suppression occur very frequently. Molecular targeted agents/kinases are undergoing clinical testing; however no final recommendations can be made. Conclusions: Currently, several re-treatment options with only modest efficacy exist. The relative value of each approach compared to other options is unknown as well as it remains open which sequence of modalities should be chosen.     

经典名方当归补血汤物质基准量值传递分析

为阐明当归补血汤物质基准的关键质量属性,通过制备21批物质基准,分别建立2套当归补血汤物质基准指纹图谱及其含量测定的检测方法,明确其指纹图谱的峰归属,相似度范围,浸出物范围,指标性成分阿魏酸、毛蕊异黄酮葡萄糖苷和黄芪甲苷的含量以及转移率范围.结果 表明,不同批次物质基准的指标性成分含量和转移率如下:当归中指标性成分阿魏...     

The role of nuclear receptors in pharmacokinetic drug-drug interactions in oncology

Drug-drug interactions can have a major impact on treatment outcome in cancer patients. These patients are at high risk of such interactions, because they are treated with combinations of multiple cytotoxic anticancer drugs or hormonal agents often co-administered with prophylactic antiemetics and analgesics to provide palliation. Interactions between drugs can affect the pharmacokinetics of concomitantly administered chemotherapeutic agents. Especially, due to the specific properties of anticancer drugs, such as a narrow therapeutic index and steep dose-toxicity curve, small pharmacokinetic changes can have significant clinical consequences like decreased therapeutic efficacy or increased toxicity. An important mechanism that underlies these interactions is the induction of enzymes or efflux transporters involved in the biotransformation and clearance of anticancer drugs. Several nuclear receptors, like the pregnane X receptor (PXR), constitutively androstane receptor (CAR), have been shown to regulate induction. Activation of these receptors will lead to induction of important enzymes like cytochrome P450 3A4 (CYP3A4), which is involved in the biotransformation of more than 50% of all clinically used drugs. Therefore, concomitant administration of agents that activate PXR will affect the pharmacokinetics of drugs that are substrate for PXRs target genes, which include CYP3A4 and MDR-1. Understanding of the molecular mechanisms that underlie enzyme induction and the identification of (new) drugs involved in pharmacokinetic drug-drug interactions may contribute to the predictability of drug-drug interactions and eventually help to develop safer anticancer regimens.