双氢青蒿素纳米结构脂质载体在荷S180瘤小鼠体内的抗肿瘤活性及生物分布研究(英文)

近年来脂质纳米粒由于其优越的特征备受青睐。本文通过腹腔注射评价了双氢青蒿素纳米结构脂质载体在荷S180瘤小鼠体内的抗肿瘤作用, 以及在荷S180昆明鼠内的生物分布研究。结果表明双氢青蒿素纳米结构脂质载体显著抑制了肿瘤的增长, 通过腹腔给药在20, 40和80mg/kg时肿瘤抑制率分别为71.24%, 79.20%和85.74%, 在荷S180小鼠体内静脉注射双氢青蒿素纳米结构脂质载体后, 药物的生物分布表明双氢青蒿素纳米结构脂质载体与双氢青蒿素溶液相比, 双氢青蒿素纳米结构脂质载体显示了明显不同的生物分布。因此, 本文实验结果确实证明了双氢青蒿素纳米结构脂质载体与双氢青蒿素普通混悬液相比, 在相同剂量下双氢青蒿素纳米结构脂质载体显示出更优越的抗肿瘤作用和剂量依赖性。     

The Effects of Lidocaine Used in Sciatic Nerve on the Pharmacodynamics and Pharmacokinetics of Ropivacaine in Sciatic Nerve Combined with Lumbar Plexus Blockade: A Double‐Blind,Randomized Study

In this controlled, randomized, double‐blind study, we compared the pharmacodynamics and pharmacokinetics of ropivacaine and staged injection of lidocaine and ropivacaine in a combined lumbar plexus–sciatic nerve block. The experiment was performed in two parts: pharmacodynamics study (Group r, n = 20; Group lr, n = 20) and pharmacokinetics study (Group R, n = 10; Group LR, n = 10). The sciatic nerve blockade was performed using either (1) 10 mL of 2% lidocaine and then 10 mL of 0.75% ropivacaine (Group lr and Group LR) or (2) 10 mL of normal saline (N.S.) and then 10 mL of 0.75% ropivacaine (Group r and Group R). Two kinds of solutions were ‘staged’ injection. The sensory onset time and sensory recovery time were assessed in the pharmacodynamics study. Arterial blood samples were collected for the pharmacokinetics study. Sciatic sensory block onset times were reduced, and the sensory recovery times were decreased in Group lr. C_max of ropivacaine in Group LR was significantly higher than that in Group R. A significant increase in AUC_(0–t) and AUC_(0–∞) was observed in Group LR compared with Group R. When 2% lidocaine and 0.75% ropivacaine are used for a combined sciatic nerve–lumbar plexus block by ‘staged’ injection, lidocaine induced faster onset times, decreased the block duration and increased the AUC and C_max of ropivacaine.     

儿童肺炎支原体感染的肺外表现临床分析

目的分析儿童肺炎支原体(MP)感染肺外器官受累的临床特征和治疗方法。方法采用SERODIA-MYCO II被动凝集法检测MP-IgM,对确诊为MP感染的患儿245例进行回顾性分析。结果患儿多集中在学龄前期及学龄期,203例以呼吸道症状为首发表现,42例以肺外器官受累症状为首发表现。肺外器官受累以神经、消化、泌尿、血液系统等多见,全部患儿经大环内酯类抗菌药物治疗3~4周后,达到临床痊愈。结论儿童MP感染除呼吸系统受累外,肺外脏器受累发生率明显升高;尤以肺外表现为首发症状时,更易造成误诊。所以对于不典型病例者应及时进行相关检测,以及早确诊,对因治疗。     

Expression profiles of hippocampal regenerative sprouting-related genes and their regulation by E-64d in a developmental rat model of penicillin-induced recurrent epilepticus

E-64d (a calpain and autophagy inhibitor) has previously been shown safe for the treatment of Alzheimer's disease in humans. In the present study, the potential protective mechanism of E-64d on hippocampal aberrant mossy fiber sprouting was examined in a developmental rat model of penicillin-induced recurrent epilepticus. A seizure was induced by penicillin every other day in Sprague–Dawley rats from postnatal day 21 (P21). The rats were randomly assigned into the control group (CONT1), the control plus E-64d (CONT2), the seizure group (EXP1) and the seizure plus E-64d (EXP2). On P51, mossy fiber sprouting and related gene expression in hippocampus were assessed by Timm staining and real-time RT-PCR methods, respectively. To validate the RT-PCR results, western blot analysis was performed on selected genes. E-64d obviously suppressed the aberrant mossy fiber sprouting in the supragranular region of dentate gyrus and CA3 subfield of hippocampus. Among the total twelve genes, six genes were strongly up- (MT-3, ACAT1, clusterin and ApoE) or down- (ZnT-1 and PRG-3) regulated by developmental seizures (EXP1) compared with that in the CONT1. Up-regulation of ApoE and Clusterin was blocked by pretreatment with E-64d both in mRNA and protein levels. Further, E-64d-pretreated seizure rats (EXP2) showed a significant downregulation of mRNA expression of PRG-1, PRG-3 and PRG-5, cathepsin B and ApoE, as well as up-regulated nSMase and ANX7 in hippocampus when compared with EXP1 rats. The results of the present study suggest that E-64d, an elective inhibitor of calpain and autophagy, is potentially useful in the treatment of developmental seizure-induced brain damage both by regulating abnormal zinc signal transduction and through the modulation of altered lipid metabolism via ApoE/clusterin pathway in hippocampus.     

Population pharmacokinetics of ciclosporin in Chinese children with aplastic anemia: effects of weight,renal function and stanozolol administration

Aim:

To develop a population pharmacokinetic model for the immunosuppressant ciclosporin in Chinese children with aplastic anemia and to identify covariates influencing ciclosporin pharmacokinetics.

Methods:

A total of 102 children with either acquired or congenital aplastic anemia aged 8.8±3.6 years (range 0.9–17.6 years) were included. Therapeutic drug monitoring (TDM) data for ciclosporin were collected. The population pharmacokinetic model of ciclosporin was described using the nonlinear mixed-effects modeling (NONMEM) VI software. The final model was validated using bootstrap and normalized prediction distribution errors.

Results:

A one-compartment model with first-order absorption and elimination was developed. The estimated CL/F was 15.1, which was lower than those of children receiving stem cell or kidney transplant reported in the West (16.9–29.3). The weight normalized CL/F was 0.45 (range: 0.27–0.70) Lh⁻¹·kg⁻¹. The covariate analysis identified body weight, serum creatinine and concomitant administration of the anabolic steroid stanozolol as individual factors influencing the CL/F of ciclosporin.

Conclusion:

Our model could be used to optimize the ciclosporin dosing regimen in Chinese children with aplastic anemia.     

Antimycotic Activity of 20 Plants from Colombian Flora

Abstract

The antifungal activities of 65 extracts were evaluated through the agar well diffusion method in 22 plant samples from the Ucumari Natural Regional Park (UNRP). These samples belong to 20 plant species related to the following botanic families: Asteraceae, Euphorbiaceae, Melastomataceae, Podocarpaceae, Rubiaceae and Solanaceae. The plant extracts were obtained in hexanes, dichloromethane and methanol. The 65 extract samples were tested against pathogenic fungi Aspergillus fumigatus (ATCC 1022), Candida albicans (ATCC 18804) and Fusarium solani (ATCC 11712). Ketoconazole was used as positive control. The methanol extracts from Solanum spp. (FJR 3155) and Tibouchina grossa exhibited the greatest inhibitory activity against the three fungi tested, while the methanol extracts from Hyeronima macrocarpa, Miconia lehmannii, and Sapium stylare inhibited two of the fungi assayed. The dichloromethane extracts from Miconia lehmannii Cong, Lycinathes acutifolia and Solanum spp. (FJR 3155) inhibited two of the three fungi tested, while the dichloromethane extracts from Cinchona pubescens Vahl and Palicourea spp. (FJR 3182) inhibited one of the three microorganism tested. Only one of the hexane extracts produced activity against the three fungi tested.     

Pharmaceutical Technology Licensing: An Analysis in the Field of Cardiovascular Disease

The technological flows and licensing across institutions plays an essential role in the process of pharmaceutical innovation by integrating the competing resources of different institutions and sharing the costs and risks, especially in the current era of open innovation. This article aims to generally describe technology licensing activities on cardiovascular drugs and, based on visualizing technology flows at different stages, to further investigate the multistage leading performers and their licensing strategies. From the IMS R&D Focus, a world-leading database in the healthcare industry, the research sample comprises 632 licensing inventions for cardiovascular drugs from 1980 to 2014. Furthermore, a network-based approach is employed to visualize the technology flows by setting nodes to represent licensing institutions and edges for licensing behavior, and further to analyze institution leaders and licensing strategies through various indicators, e.g., out-degree, in-degree, and betweenness centrality. The results show that technology licensing networks gradually transformed from sparse to dense from the preclinical to marketed stages. There is obvious synergy and complementation among universities, multinational enterprises, and mid- and small-sized enterprises. R&D organizations represented by universities denote themselves as upstream in the pharmaceutical R&D chain. As a hub, multinational enterprises play an important role as technology integrators and show the most frequent technology licensing, both in technology inflows and outflows, whereas various small firms are viewed as satellite partners around multinational enterprises. This work provides valuable insights for pharmaceutical researchers, investors, policymakers, and technology brokers not only in the field of the discovery of cardiovascular drugs but also of other therapeutic drugs.     

(S)-1-(N-烯丙氧羰基)亚胺乙基-3-巯基吡咯烷的合成

目的 合成帕尼培南关键中间体 (S)-1-( N-烯丙氧羰基)亚胺乙基-3-巯基吡咯烷。方法 以氯甲酸烯丙酯为酰化剂,与盐酸乙脒进行 N-酰化反应得到 1-亚胺乙基氨基甲酸烯丙酯,该化合物与 3-R-羟基吡咯烷进行缩合,再经甲磺酰化、S_N2 取代、水解共 5 步反应得到目标化合物。结果与结论 该合成路线中使用新型保护基烯丙氧羰基替代传统的保护基—对硝基苄氧羰基,目标化合物的结构经 ¹H-NMR、MS 谱确证,总收率为 41.6%,各步反应操作简便,条件温和,有利于工业化生产。     

HPLC法测定复方柳安咖注射液中水杨酸钠、安替比林和咖啡因的含量

目的建立HPLC法测定复方柳安咖注射液中水杨酸钠、安替比林和咖啡因的含量。方法色谱柱:Agela TechnologiesC18柱(150mm×4.6mm,5μm);流动相:0.02mol.L-1磷酸二氢钠溶液(用磷酸调节pH 2.6)-乙腈-甲醇(70∶15∶15);检测波长:280nm;柱温:35℃;流速:1.0mL.min-1;进样量:20μL。结果水杨酸钠、安替比林和咖啡因线性范围分别为13.79～124.1(r=0.999 9),4.016～36.14(r=0.999 9)和2.078～18.70μg.mL-1(r=0.999 9);平均回收率分别为100.1%(RSD为0.5%),100.0%(RSD为0.5%)和100.5%(RSD为0.4%)。结论该方法灵敏、准确、快速,专属性强,可有效地控制复方柳安咖注射液中水杨酸钠、安替比林、咖啡因的含量。     

大豆异黄酮和钙对去卵巢大鼠骨密度及微量元素的影响

目的 :探讨大豆异黄酮和钙对去卵巢大鼠的骨密度及微量元素的影响。方法 :2 8只雌性SD大鼠随机分为假手术组、去卵巢组、去卵巢补钙组 [5 0mg/ (kg·d) ]和去卵巢加大豆异黄酮组 [大豆异黄酮 10 0mg/ (kg·d) ],10周后测骨密度和骨矿物含量及血清、尿液和骨骼钙、锌、铜、铁含量。结果 :实验结束后 ,去卵巢后大鼠的骨密度和骨矿物含量、骨骼钙、锌、铜、铁和血清锌、铁显著下降 ,血清钙、铜、ALP及尿钙、铜、铁显著性增高(P <0 0 1和P <0 0 5 ) ;与单纯去卵巢组比 ,大豆异黄酮组大鼠的骨密度、骨矿物含量、血清锌 ,骨骼中钙、锌、铜显著升高 ,血清钙、铜、ALP及尿钙、铜显著性下降 (P <0 .0 1和P <0 .0 5 ) ,而补钙组各指标都无显著性意义。结论 :大豆异黄酮可预防去卵巢大鼠骨钙、锌、铜丢失 ,预防骨质疏松。