The predictive utility of the plant phylogeny in identifying sources of cardiovascular drugs

Context: Cardiovascular disease (CVD) is the number one cause of death globally, responsible for over 17 million (31%) deaths in the world. Novel pharmacological interventions may be needed given the high prevalence of CVD.

Objective: In this study, we aimed to find potential new sources of cardiovascular (CV) drugs from phylogenetic and pharmacological analyses of plant species that have experimental and traditional CV applications in the literature.

Materials and methods: We reconstructed the molecular phylogeny of these plant species and mapped their pharmacological mechanisms of action on the phylogeny.

Results: Out of 139 plant species in 71 plant families, seven plant families with 45 species emerged as phylogenetically important exhibiting common CV mechanisms of action within the family, as would be expected given their common ancestry: Apiaceae, Brassicaceae, Fabaceae, Lamiaceae, Malvaceae, Rosaceae and Zingiberaceae. Apiaceae and Brassicaceae promoted diuresis and hypotension; Fabaceae and Lamiaceae had anticoagulant/thrombolytic effects; Apiaceae and Zingiberaceae were calcium channel blockers. Moreover, Apiaceae, Lamiaceae, Malvaceae, Rosaceae and Zingiberaceae species were found to possess anti-atherosclerotic properties.

Discussion and conclusions: The phylogeny identified certain plant families with disproportionately more species, highlighting their importance as sources of natural products for CV drug discovery. Though there were some species that did not show the same mechanism within the family, the phylogeny predicts that these species may contain undiscovered phytochemistry, and potentially, the same bioactivity. Evolutionary pharmacology, as applied here, may guide and expedite our efforts in discovering sources of new CV drugs.     

韩国生物类似药注册管理法规体系概况

随着生物技术产业的发展,韩国开始把重点放在提升生物医药制造和临床标准上,逐步从生产仿制药转变为开发更多新分子实体、生物制品和生物类似药。2009年韩国发布了《生物类似药评估指南》,2010年推行了动态药品生产管理规范(c GMP),目前韩国大多数工厂都通过了美国FDA和欧盟药品局(EMA)检查,韩国公司与跨国生物医药公司的合作也越加紧密。从注册分类、注册程序和技术指南体系方面对韩国生物类似药注册管理法规体系做出框架性梳理。     

Budgetary Impact and Cost Drivers of Drugs for Rare and Ultrarare Diseases

Objectives

To review recent studies reporting health care expenditures (budgetary impact) for orphan medicinal products (OMPs) in Europe and to contribute to our understanding of the cost drivers of nononcological OMPs by means of an empirical analysis in Germany.

Urinary metal concentrations among mothers and children in a Mexico City birth cohort study

Personal care product use is a potential source of metals exposure among children, but studies have been limited. We measured urinary concentrations of 10 metals (aluminum, arsenic [As], barium [Ba], cadmium, cobalt [Co], lead [Pb], manganese [Mn], molybdenum [Mo], nickel, and zinc [Zn]) in third trimester pregnant women (n?=?212) and their children at 8–14 years of age (n?=?250). Demographic factors (child sex, age, socioeconomic status, and maternal education), body mass index (BMI) z-score, and child personal care product use in the 24?h prior to urine collection were examined as predictors of urinary metal concentrations. Metals were detected in 80–100% of urine samples, with significant differences in maternal versus childhood levels. However, metal concentrations were not strongly correlated within or between time points. In linear regression models including all demographic characteristics, BMI z-score, and specific gravity, age was associated with higher Co (6% [95% CI: 2, 10]), while BMI z-score was associated with lower Mo (-6% [95% CI: -11, -1). In addition, significantly higher metal concentrations were observed among users of colored cosmetics (Mo: 42% [95% CI: 1, 99]), deodorant (Ba: 28% [3, 58]), hair spray/hair gel (Mn: 22% [3, 45]), and other toiletries (As: 50% [9, 108]), as well as with an increasing number of personal care products used (As: 7% [3, 11]) after adjustment for child sex, age, total number of products used, and specific gravity. However, significantly lower metal concentrations were noted for users of hair cream (As and Zn: -20% [-36, -2] and -21% [-35, -2], respectively), shampoo (Pb: -40% [-62, -7]), and other hair products (Pb: -44% [-65, -9]). We found that personal care product use may be a predictor of exposure to multiple metals among children. Further research is recommended to inform product-specific exposure source identification and related child health risk assessment efforts.     

我国甘草及其制品进出境调查研究

甘草应用广泛,自古有"十方九草"之说。但是随着工业化生产需求的增加,我国甘草资源迅速减少,我国开始从哈萨克斯坦、乌兹别克斯坦等进口甘草资源。为了摸清我国甘草贸易流向和评估我国甘草在世界甘草贸易中的地位,通过对我国海关甘草及其制品2011—2015年5年的贸易情况调查和分析,提出我国甘草及其制品在国际贸易中存在的问题:我国甘草进出口量双双下滑;我国甘草国际贸易进出口量较为集中,贸易风险较大;存在出口配额管理执行不到位的现象。提出了我国甘草资源作为医药战略资源的一种,必须立足国内发展,出口配额管理由被动配额转向主动配额管理,提升我国甘草资源内在价值,确立我国甘草及其制品的国际市场地位,以及掌控国际市场定价权力。     

对于阴火的新认识

阴火的概念首见于李东垣的《内外伤辨惑论》,详实于《脾胃论》,但其中并没有对阴火的本质做出详细解释,因此后世医家对其有很多不同见解。主要包括:气虚发热、阴虚发热、相火离位、阴火非火四种观点,但是以上观点仍不能较全面解释阴火。现通过复习李东垣对于阴火的论述,并结合个人对气机循环的理解,同时应用以方测证的方法,得出阴火的本质是脾胃之气在受劳倦,饥饱失宜或七情内伤的情况下,脾胃的运化和受纳腐熟的功能受损,产生的一种病理产物。补中益气汤治疗阴火的原理为健运中焦,恢复脾胃运化谷食的正常功能,使阴火所生乏源,再以风药泻之,则元气复,阴火散。     

枳壳不同炮制品的燥性比较及其对功能性消化不良大鼠胃肠功能的影响

目的:比较枳壳不同炮制品的燥性,考察其对功能性消化不良(FD)大鼠胃肠功能的影响。方法:以大鼠饮水量、排尿量、肾水通道蛋白3(AQP3)含量、血清环磷酸腺苷(c AMP)与血清环磷酸鸟苷(c GMP)比值为评价指标,观察不同剂量的枳壳生品、麸炒枳壳、蜜麸枳壳对健康大鼠水液代谢的影响;以胃黏膜损伤指数,血清肿瘤坏死因子-α(TNF-α),白细胞介素6(IL-6),IL-8含量为评价指标,观察不同剂量枳壳生品、麸炒枳壳、蜜麸枳壳对健康大鼠胃黏膜损伤的影响;以大鼠胃残留率和小肠推进率,血清胃动素(MTL),血管活性肠肽(VIP),降钙素基因相关肽(CGRP)含量为评价指标,观察不同剂量枳壳生品、麸炒枳壳、蜜麸枳壳对FD大鼠胃肠功能的影响。结果:在水液代谢方面,同等剂量给药组与空白组相比,差异性排序为枳壳生品麸炒枳壳蜜麸枳壳,且高剂量组低剂量组;在胃黏膜损伤方面,不同剂量枳壳生品、麸炒枳壳、蜜麸枳壳组各项指标与空白组比较均无显著性差异;在促胃肠动力方面,同等剂量给药组与模型组相比,差异性为麸炒枳壳枳壳生品蜜麸枳壳,且低剂量组高剂量组。结论:枳壳生品的燥性主要表现为对机体津液的损伤,且强度与剂量有关,对健康大鼠胃黏膜未见明显直接刺激。炮制后可在一定程度上缓和伤津之弊,且以蜜麸枳壳缓和作用最佳;枳壳生品和炮制品均可促进FD大鼠胃肠功能的恢复,麸炒枳壳治疗作用优于生品与蜜麸制品。     

口腔细菌终末代谢酸的反相梯度高效液相色谱法分析条件研究

目的:探讨测定口腔细菌终末代谢酸的反相梯度高效液相色谱法最佳分析条件。方法:采用高效液相色谱技术梯度洗脱程序,流速110~210 mlPmin,检测波长217 nm,流动相为60% 012 molPL磷酸盐甲醇溶液pH218,对常见的细菌终末代谢酸进行不同培养基、pH值、温度、萃取液、沉淀剂等分析条件进行研究。结果:口腔细菌在牛心脑浸液(BHI)培养液中经48 h厌氧培养,上清液在pH 117的酸度下用乙醚提取可得到理想的色谱分析结果。结论:该方法可推广应用于细菌终末代谢酸鉴定。     

Differential expression of salivary S100A7 in oral submucous fibrosis

Aim

To investigate the expression of salivary S100A7 levels among patients with oral submucous fibrosis (OSF) and healthy controls.

晚期糖基化终末产物受体在2型糖尿病伴牙周炎患者牙龈中表达

目的:探讨晚期糖基化终末产物受体(RAGE)在非胰岛素依赖型糖尿病伴发牙周炎患者牙龈组织中的分布及其在牙周组织破坏中的作用。方法:用免疫组化方法检测9名患者共20个位点牙龈组织中RAGE和肿瘤坏死因子α(TNF-α)的分布,并进行了半定量检测。其中慢性牙周炎(CP)患者5名,非胰岛素依赖型糖尿病(NIDDM)伴发牙周炎患者4名。同时,应用酶联免疫吸附测定法(ELISA)对相应位点龈沟液及外周血中的白细胞介素6(IL-6)及TNF-α进行测量。结果:RAGE阳性细胞在2组的龈组织中的差异具有极显著性,且RAGE的表达与TNF-α的表达显著相关(P<0.05)。2组龈沟液中IL-6及TNF-α浓度的差异无显著性,但二者的浓度在NIDDM组有高于CP组的趋势。结论:RAGE参与了NIDDM伴发牙周炎患者的牙周组织的破坏。