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Cancer, chitosan nanoparticles and catalytic nucleic acids. 癌症,壳聚糖纳米颗粒和催化核酸。
Pub Date : 1900-01-01 DOI: 10.1211/jpp/61.01.0002
M. Tan, P. Choong, C. Dass
OBJECTIVESThe aim of this review was to examine gene therapy involving DNAzyme and siRNA encapsulation into chitosan nanoparticles, discussing the current and future status of this drug delivery system in enhancing drug delivery and cancer therapy.KEY FINDINGSCancer is a disease state in which the cells in our body undergo mutations at the genetic level and are transformed, acquiring the ability to replicate limitlessly. Conventional cancer treatment involves the use of surgery and cytotoxic chemotherapy and/or radiotherapy, which have the potential of harming normal, otherwise healthy, non-neoplastic cells. Newer forms of therapy such as immunotherapy and gene therapy have shown initial promise, but still require better ways to limit exposure to cancerous lesions in the body. As a result drug delivery systems have been developed in attempts to deliver therapeutics specifically to the target lesion site. One recent drug delivery system has revolved around the use of chitosan nanoparticle technology, where therapeutics are encapsulated into nanoparticles and targeted to tumours.SUMMARYThough few, attempts at encapsulating therapeutics such as deoxyribozymes and small or short interfering RNA have been optimistic and encouraging.
目的综述壳聚糖纳米颗粒包封DNAzyme和siRNA的基因治疗方法,探讨该药物传递系统在增强药物传递和癌症治疗中的现状和未来发展。癌症是一种疾病状态,在这种状态下,我们体内的细胞在基因水平上发生突变并被转化,从而获得了无限复制的能力。传统的癌症治疗包括使用手术和细胞毒性化学疗法和/或放射疗法,这些疗法有可能损害正常的、健康的非肿瘤细胞。新的治疗方法,如免疫疗法和基因疗法已经显示出初步的希望,但仍然需要更好的方法来限制暴露于体内的癌症病变。因此,药物输送系统已经被开发出来,试图将治疗药物特异性地输送到目标病变部位。最近的一种药物输送系统围绕着壳聚糖纳米颗粒技术的使用,这种技术将治疗药物包裹在纳米颗粒中,并靶向肿瘤。虽然很少,但在封装治疗药物如脱氧核酶和小或短干扰RNA方面的尝试是乐观和令人鼓舞的。
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引用次数: 37
Curcuma zedoaria Rosc. (white turmeric): a review of its chemical, pharmacological and ethnomedicinal properties. 莪术(白姜黄):其化学、药理和民族医药性质的综述。
Pub Date : 1900-01-01 DOI: 10.1211/jpp/61.01.0003
R. Lobo, K. Prabhu, A. Shirwaikar, A. Shirwaikar
OBJECTIVESCurcuma zedoaria Rosc is a perennial herb found in tropical countries, such as India, Japan and Thailand. Various parts of this plant are used in Ayurveda and other folk medicines for the treatment of different ailments such as diarrhoea, cancer, flatulence and dyspepsia. This study is an attempt to compile an up-to-date and comprehensive review of C. zedoaria that covers its traditional and folk medicinal uses, phytochemistry and pharmacology.KEY FINDINGSResearch carried out using different in-vitro and in-vivo techniques of biological evaluation supports most of the claims.SUMMARYThis review presents the botany, chemistry, traditional uses and pharmacological data of the plant.
目的莪术(curcuma zedoaria Rosc)是一种生长于印度、日本和泰国等热带国家的多年生草本植物。这种植物的不同部分被用于阿育吠陀和其他民间药物,用于治疗不同的疾病,如腹泻、癌症、肠胃胀气和消化不良。本研究旨在对莪术的传统和民间药用、植物化学和药理学等方面进行全面的综述。主要发现使用不同的体外和体内生物评估技术进行的研究支持了大多数说法。综述了该植物的植物学、化学、传统用途和药理资料。
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引用次数: 161
Effect of traditional Chinese herbal Bu-Wang-San on synaptic plasticity in ovariectomised rats. 补王散对去卵巢大鼠突触可塑性的影响。
Pub Date : 1900-01-01 DOI: 10.1211/jpp/61.01.0013
Hui Li, Shu-ling Li, Zhi-hong Wu, Li Gong, Jiu-Ling Wang, Yu-Zhu Li
OBJECTIVESThe neuroprotective effects of Bu-Wang-San (BWS) and its effects on spine synapse plasticity were investigated in ovariectomised rats.METHODSThirty-six ovariectomised rats were divided into three groups: untreated controls, treatment with 17beta-estradiol or with BWS. After 3 months, spatial acquisition and spatial retention were measured using the Morris water maze. Swim time, swim distance, swim speed, quadrant time and platform crossing were recorded. Spine synapse density in the hippocampus was examined by transmission electron microscopy. The expression of synaptophysin P38 (P38) mRNA was examined by real-time PCR and the protein expression of P38 was examined by Western blot.KEY FINDINGSIn spatial acquisition and spatial retention, the BWS group functioned significantly better than the control group. Ultrastructural observation of the hippocampus showed that BWS significantly increased spine synapse density compared with the ovariectomised group. In addition, BWS significantly increased P38 mRNA and protein expression in the hippocampus. Thus, the positive effect of BWS on learning and memory in rats was associated with increased spinal synapse density and increased P38 mRNA and protein expression in the hippocampus following menopause-induced injury.CONCLUSIONSThese results suggest that BWS could improve cognitive ability following menopause-induced impairment of learning and memory.
目的观察补王散对去卵巢大鼠的神经保护作用及其对脊髓突触可塑性的影响。方法36只切除卵巢的大鼠分为3组:对照组、17 -雌二醇组和BWS组。3个月后,采用Morris水迷宫测量空间习得和空间保留。记录游泳时间、游泳距离、游泳速度、象限时间、过台情况。透射电镜观察海马棘突触密度。实时荧光定量PCR检测synaptophysin P38 mRNA的表达,Western blot检测P38蛋白的表达。在空间习得和空间保留方面,BWS组明显优于对照组。海马超微结构观察显示,与去卵巢组相比,BWS显著增加了脊柱突触密度。此外,BWS显著提高了海马P38 mRNA和蛋白的表达。由此可见,BWS对大鼠学习记忆的积极作用与绝经损伤后脊髓突触密度增加、海马P38 mRNA和蛋白表达增加有关。结论BWS可改善绝经期学习记忆障碍患者的认知能力。
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引用次数: 7
HYPOGLYCAEMIC AGENTS. 那些代理。
Pub Date : 1900-01-01 DOI: 10.1201/9781315383293-33
D. F. Hayman, V. Petrow, O. Stephenson
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引用次数: 3
Inhibitory effect of quercetin on rat trachea contractility in vitro. 槲皮素对体外大鼠气管收缩性的抑制作用。
Pub Date : 1900-01-01 DOI: 10.1211/jpp/61.01.0016
R. Capasso, G. Aviello, B. Romano, Giuseppina Atorino, E. Pagano, F. Borrelli
OBJECTIVESThe effect of quercetin, a naturally occurring flavonoid traditionally used to treat airway diseases such as bronchial asthma, on the contractile response elicited by electrical field stimulation or carbachol in rat isolated trachea was investigated.METHODSIsolated tracheal tissue was subjected to contractions by an electrical field stimulation of 5 Hz for 30 s, 400 mA, and the responses in the presence of cumulative concentrations of quercetin (10(-6)-3x10(-4) M) were observed. The effect of quercetin was also evaluated after administration of phentolamine plus propranolol (to block alpha- and beta-adrenergic receptors), NG-nitro-L-arginine methyl ester (to block nitric oxide synthesis), capsaicin (to desensitise sensory C fibres), alpha-chymotrypsin (a proteolytic enzyme that rapidly degrades vasoactive intestinal peptide), SR140333 and SR48968 (tackykinin NK1 and NK2 receptor antagonists, respectively).KEY FINDINGSQuercetin produced a concentration-dependent inhibition of contractions induced by both carbachol and electrical field stimulation. However, quercetin was more active in inhibiting the contractions produced by electrical field stimulation than those induced by carbachol, suggesting a presynaptic site of action (in addition to a postsynaptic effect, as revealed by the inhibitory action of quercetin on carbachol-induced contractions). The inhibitory effect of quercetin on contractions induced by electrical field stimulation was unaffected by phentolamine plus propranolol, SR 140333 and SR 48968, capsaicin treatment or by the proteolytic enzyme alpha-chymotrypsin. In contrast, the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester significantly reduced the inhibitory effect of quercetin on contractions induced by electrical field stimulation.CONCLUSIONSQuercetin inhibits rat tracheal contractility through a presynaptic (involving nitric oxide) and a postsynaptic site of action.
目的研究槲皮素(一种天然存在的类黄酮,传统上用于治疗支气管哮喘等气道疾病)对大鼠离体气管电场刺激或苯酚引起的收缩反应的影响。方法对离体气管组织施加5 Hz、400 mA、30 s的电场刺激,观察槲皮素(10(-6)-3 × 10(-4) M)累积浓度下的收缩反应。槲皮素的作用也在给予酚特拉明加心得安(阻断α和β肾上腺素能受体)、ng -硝基- l -精氨酸甲酯(阻断一氧化氮合成)、辣椒素(使感觉C纤维脱敏)、α -凝乳胰蛋白酶(一种快速降解血管活性肠肽的蛋白水解酶)、SR140333和SR48968(分别为抗凝素NK1和NK2受体拮抗剂)后进行了评估。squercetin对由苯酚和电场刺激引起的收缩产生浓度依赖性抑制。然而,槲皮素在抑制电场刺激引起的收缩方面比碳水化合物诱导的收缩更活跃,这表明槲皮素在突触前起作用(除了突触后作用,槲皮素对碳水化合物诱导的收缩的抑制作用也揭示了这一点)。酚妥拉明加心得安、SR 140333和SR 48968、辣椒素和α -凝乳胰蛋白酶对槲皮素对电场刺激引起的收缩的抑制作用不受影响。相反,一氧化氮合酶抑制剂ng -硝基- l -精氨酸甲酯显著降低槲皮素对电场刺激引起的收缩的抑制作用。结论squercetin通过突触前(涉及一氧化氮)和突触后作用位点抑制大鼠气管收缩。
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引用次数: 20
Effects of cytochrome P450 inducers and inhibitors on the pharmacokinetics of intravenous furosemide in rats: involvement of CYP2C11, 2E1, 3A1 and 3A2 in furosemide metabolism. 细胞色素P450诱导剂和抑制剂对大鼠静脉注射速尿药动学的影响:CYP2C11、2E1、3A1和3A2参与速尿代谢
Pub Date : 1900-01-01 DOI: 10.1211/jpp/61.01.0007
Kyung H. Yang, Young H. Choi, U. Lee, Joo H. Lee, Myung G. Lee
OBJECTIVESIt has been reported that the non-renal clearance of furosemide was significantly faster in rats pretreated with phenobarbital but was not altered in rats pretreated with 3-methylcholanthrene. However, no studies on other cytochrome P450 (CYP) isozymes have yet been reported in rats.METHODFurosemide 20 mg/kg was administered intravenously to rats pretreated with various CYP inducers--3-methylcholanthrene, orphenadrine citrate and isoniazid, inducers of CYP1A1/2, 2B1/2 and 2E1, respectively, in rats--and inhibitors--SKF-525A (a non-specific inhibitor of CYP isozymes), sulfaphenazole, cimetidine, quinine hydrochloride and troleandomycin, inhibitors of CYP2C6, 2C11, 2D and 3A1/2, respectively, in rats.KEY FINDINGSThe non-renal clearance of furosemide was significantly faster (55.9% increase) in rats pretreated with isoniazid, but slower in those pretreated with cimetidine or troleandomycin (38.5% and 22.7% decreases, respectively), than controls. After incubation of furosemide with baculovirus-infected insect cells expressing CYP2C11, 2E1, 3A1 or 3A2, furosemide was metabolized via CYP2C11, 2E1, 3A1 and 3A2.CONCLUSIONSThese findings could help explain possible pharmacokinetic changes of furosemide in various rat disease models (where CYP2C11, 2E1, 3A1 and/or CYP3A2 are altered) and drug-drug interactions between furosemide and other drugs (mainly metabolized via CYP2C11, 2E1, 3A1 and/or 3A2).
目的有报道称,用苯巴比妥预处理的大鼠对呋塞米的非肾清除率明显加快,而用3-甲基胆蒽预处理的大鼠对呋塞米的非肾清除率没有改变。然而,其他细胞色素P450 (CYP)同工酶在大鼠体内的研究尚未见报道。方法将速尿20 mg/kg静脉滴注于经多种cypp诱导剂(3-甲基胆蒽、枸橼酸奥非那林和异烟肼,分别为大鼠CYP1A1/2、2B1/2和2E1诱导剂)和抑制剂(大鼠CYP2C6、2C11、2D和3A1/2抑制剂,SKF-525A,非特异性cypp同型酶抑制剂)预处理的大鼠。主要发现异烟肼预处理的大鼠对呋塞米的非肾清除率明显快于对照组(增加55.9%),而西咪替丁或罗莱霉素预处理的大鼠则慢于对照组(分别减少38.5%和22.7%)。将速尿与杆状病毒感染的表达CYP2C11、2E1、3A1或3A2的昆虫细胞孵育后,速尿通过CYP2C11、2E1、3A1和3A2代谢。结论这些发现有助于解释呋塞米在各种大鼠疾病模型中可能发生的药代动力学变化(CYP2C11、2E1、3A1和/或CYP3A2发生改变)以及呋塞米与其他药物(主要通过CYP2C11、2E1、3A1和/或3A2代谢)之间的药物相互作用。
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引用次数: 9
Concentration-dependent plasma protein binding of the novel dipeptidyl peptidase 4 inhibitor BI 1356 due to saturable binding to its target in plasma of mice, rats and humans. 新型二肽基肽酶4抑制剂BI 1356在小鼠、大鼠和人血浆中可饱和结合的浓度依赖性血浆蛋白结合。
Pub Date : 1900-01-01 DOI: 10.1211/jpp/61.01.0008
H. Fuchs, J. Tillement, S. Urien, A. Greischel, W. Roth
OBJECTIVESThe purpose of this study was to characterise the plasma protein binding of BI 1356.METHODSBI 1356 (proposed trade name ONDERO) is a novel dipeptidyl peptidase 4 (DPP-4) inhibitor, which is under clinical development for the treatment of type 2 diabetes. DPP-4 is expressed in various tissues but soluble DPP-4 is also present in plasma. Therefore, binding to soluble DPP-4 may influence the pharmacokinetics of BI 1356. Plasma protein binding of BI 1356 was determined in vitro for wild type mice and rats and the results compared with those for DPP-4 knockout mice and DPP-4 deficient Fischer rats. In addition, protein binding of BI 1356 was examined in plasma from healthy human volunteers and renal excretion of the compound in the DPP-4 knockout mice was compared with that occurring in wild type mice.KEY FINDINGSThe results showed that BI 1356 exhibited a prominent concentration-dependent plasma protein binding due to a saturable high affinity binding to the DPP-4 target in plasma. Differences in renal excretion of BI 1356 between DPP-4 knockout mice and wild type mice suggested that saturable binding of BI 1356 to DPP-4 in the body also influenced elimination.CONCLUSIONSHigh affinity, but readily saturable binding of BI 1356 to its target DPP-4 accounted primarily for the concentration-dependent plasma protein binding at therapeutic plasma concentrations of BI 1356.
目的研究BI 1356的血浆蛋白结合特性。方法sbi 1356(商品名ONDERO)是一种新型二肽基肽酶4 (DPP-4)抑制剂,目前正处于临床开发阶段,用于治疗2型糖尿病。DPP-4在多种组织中表达,但可溶性DPP-4也存在于血浆中。因此,与可溶性DPP-4结合可能会影响BI 1356的药代动力学。测定BI 1356在野生型小鼠和大鼠体内的血浆蛋白结合情况,并与DPP-4敲除小鼠和DPP-4缺陷Fischer大鼠进行比较。此外,我们还检测了健康人类志愿者血浆中BI 1356的蛋白结合,并比较了DPP-4基因敲除小鼠与野生型小鼠的肾脏排泄情况。结果表明,由于BI 1356与血浆中DPP-4靶点具有饱和高亲和力结合,因此表现出明显的浓度依赖性血浆蛋白结合。在DPP-4敲除小鼠和野生型小鼠之间,BI 1356在肾脏排泄的差异表明,BI 1356在体内与DPP-4的饱和结合也影响了消除。结论BI 1356与靶蛋白DPP-4具有高亲和力,但易于饱和结合,这是治疗性BI 1356血浆浓度依赖性血浆蛋白结合的主要原因。
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引用次数: 35
期刊
The Journal of pharmacy and pharmacology
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