19F核磁共振定量法测定含氟漱口液中氟化钠的含量

目的 建立¹⁹F核磁共振技术测定含氟漱口液中氟化钠含量的方法。方法 采用¹⁹F核磁共振技术,以三氟乙酸作为内标物,使用300MHz核磁共振波谱仪,在25℃下采集样品的¹⁹F核磁共振谱,建立内标标准曲线,用于氟化钠定量分析。结果 氟化钠在0.1~0.8 mg/ml范围内,线性关系良好,回归方程为A=1.1392C-0.0013,r=0.99995;低、中、高3个浓度的平均回收率分别为99.36%、99.31%、99.65%,RSD分别为0.51%、0.35%、0.54%,含氟漱口液中氟化钠的平均含量为99.30%。结论 研究建立的¹⁹F核磁共振方法准确度、精密度较好,能够快速、准确地测定含氟漱口液中氟化钠的含量。     

分化型甲状腺癌术后131I清除残余甲状腺组织的疗效及其影响因素分析

目的 探讨分化型甲状腺癌（DTC）患者术后¹³¹I清除残余甲状腺组织（简称“清甲”）的疗效及¹³¹I清甲治疗效果的影响因素。方法 收集2013年3月至2015年1月安徽省立医院行¹³¹I 清甲治疗的DTC术后患者41例,其中乳头状癌37例、滤泡状癌4例,¹³¹I清甲治疗剂量为1 110～5 550 MBq。观察¹³¹I清甲成功率;采用logistic回归分析¹³¹I清甲治疗效果的影响因素。结果 41例DTC术后患者中,¹³¹I清甲成功率为60.98%（25/41）。单因素分析显示残余甲状腺质量（χ²=8.431,P=0.006）、24 h摄¹³¹I率（χ²=7.663,P=0.015）和¹³¹I剂量（χ²=12.751,P=0.001）是影响¹³¹I疗效的因素。多因素logistic回归分析表明残余甲状腺质量（Wald=4.326,P=0.018）和¹³¹I剂量（Wald=12.320,P=0.000）是影响¹³¹I清甲治疗效果的独立因素。结论 DTC患者术后¹³¹I清甲治疗的成功率较高,残余甲状腺质量和¹³¹I剂量是影响¹³¹I清甲治疗效果的主要因素。     

用电感耦合等离子体质谱法测定钆特酸葡胺注射液中游离Gd3+的含量

目的 建立测定钆特酸葡胺注射液中Gd³⁺含量的方法。方法 电感耦合等离子体质谱（ICP-MS）法。分离柱为金属螯合柱（1-ml Chelating Sepharose column）,柱温为常温,流速为1 ml/min,进样量为0.5 ml。ICP-MS的相对分子质量为157（Gd的相对分子质量为157）,载气为氩气。结果 回归方程为：Y=0.001 635X+0.000 000E+000（经过原点）,r=1.000。线性范围为0~500 μg/L;仪器精密度、稳定性、重复性、加样回收率试验结果均符合要求。结论 该方法操作简便、结果准确、重复性好,可用于测定钆特酸葡胺注射液中Gd³⁺的含量。     

HPLC-MS/MS测定动物源性中药中的3种β2-受体激动剂残留

目的 建立动物源性中药中的克伦特罗、沙丁胺醇和莱克多巴胺3种β₂-受体激动剂残留的高效液相色谱-串联四级杆质谱（HPLC-MS/MS）检测方法。方法 以Agilent XDB-C₁₈（50 mm×4.6 mm,5.0µm）色谱柱分离,串联四级杆质谱仪检测,MRM模式进行定性定量检测分析,样品经酶解后,经MCX固相萃取柱净化,检测阿胶和人工牛黄中的克伦特罗、沙丁胺醇和莱克多巴胺。结果 3种β₂-受体激动剂质谱检测的线性范围宽,相关性好,R² ≥ 0.997 1;方法精密度RSD为1.4%~2.3%（n=6）;方法回收率范围为89.4%~102.8%;定量限范围为0.25~5.50µg·L^-1;日内精密度为2.4%~4.6%（n=5）,日间精密度为1.9%~3.7%（n=9）。结论 本方法专属性强,操作简单、快捷,可作为动物源性中药中克伦特罗、沙丁胺醇和莱克多巴胺3种β₂-受体激动剂残留的定量、定性的有效检测方法。     

VKORC1-3673G>A、CYP2C9*3、CYP4F2 rs2108622和CYP2C19*2基因多态性对中国汉族房颤患者华法林维持剂量的影响

目的 探讨VKORC1-3673G>A、CYP2C9^*3、CYP4F2 rs2108622和CYP2C19^*2位点基因多态性对中国汉族房颤患者华法林维持剂量的影响。方法 收集107例服用华法林达维持剂量的汉族房颤患者的血样和临床相关资料,应用PCR-RFLP法检测VKORC1-3673G>A、CYP2C9^*3、CYP4F2 rs2108622和CYP2C19^*2基因型,采用独立样本t检验分析基因型与华法林维持剂量的相关性。多元线性回归建立给药模型,探讨基因多态性对华法林维持剂量的影响。结果 VKORC1-3673G>A、CYP2C9^*3、CYP4F2 rs2108622基因多态性和患者年龄、体质量能解释45.2%的华法林维持剂量差异。CYP2C19^*2基因多态性对本研究人群华法林维持剂量无影响。结论 VKORC1-3673G>A、CYP2C9^*3、CYP4F2 rs2108622基因多态性显著影响中国汉族房颤患者的华法林维持剂量。     

UPLC-MS/MS测定减肥食品中8种非法添加化学成分

目的 建立一种简便有效检测减肥食品中非法添加化学成分的UPLC-MS/MS检测方法。方法 采用UPLC-MS/MS法,以Eclipse Plus C₁₈（2.1 mm×50 mm,1.8 μm）色谱柱分离,串联四级杆质谱仪检测,多反应监测模式进行定性定量分析,以流动相A（0.02 mol·L^-1乙酸铵水溶液）-B（甲醇）进行梯度洗脱;柱温：40℃;流速：0.3 mL·min^-1,进样量2 μL。样品以甲醇为溶剂超声提取,快速定性定量检测非法添加在减肥食品中的麻黄碱、咖啡因、呋塞米、芬氟拉明、酚酞、N-单去甲基西布曲明、N,N-双去甲基西布曲明、西布曲明8种化学成分。结果 8种减肥类化学成分质谱检测的线性范围宽,相关性R² ≥ 0.995;方法检测限为0.042~0.175 μg·mL^-1,定量限为0.126~0.525 μg·mL^-1,方法精密度RSD（n=6）为1.7%~4.7%;3个浓度水平的平均回收率为90.3%~105.1%。结论 本方法专属性强、操作简单、方便快捷,可作为食品中非法添加减肥类化学成分的有效检测方法。     

LC-MS/MS测定中成药中非法添加物N-乙基他达拉非

目的 建立LC-MS/MS定性及定量测定中成药中非法添加N-乙基他达拉非。方法 采用DAD检测器进行初步定性筛查,用质谱检测器进行定性确证,再用DAD检测器进行定量。初筛及定量选用SHISEIDO C₁₈柱（250 mm×4.6 mm,5 μm）,以流动相A[磷酸三乙胺溶液（取三乙胺7 mL,用水稀释至1 000 mL,用磷酸调pH至2.8）-甲醇-乙腈（60：20：20）]与流动相B[磷酸三乙胺溶液（取三乙胺7 mL,用水稀释至1 000 mL,用磷酸调pH至2.8）-甲醇-乙腈（8：46：46）]梯度洗脱,体积流量1 mL·min^-1,检测波长230 nm;确证选用Dikma Spursil C₁₈柱（150 mm×2.1 mm,3 μm）,以甲醇-乙腈-含0.1%冰乙酸的0.02 mol·L^-1乙酸铵溶液（30：25：45）等度洗脱,体积流量0.2 mL·min^-1。结果 N-乙基他达拉非质量浓度在0.003~0.3 mg·mL^-1内与峰面积有良好线性关系,平均回收率为97.8%,RSD为0.7%（n=9）;通过对30批次壮阳类中成药进行测定,其中2批检测结果为阳性,含量分别为4.8,4.1 mg·g^-1。结论 该方法快速、准确、灵敏度高,可作为分析检测壮阳类中成药中非法添加N-乙基他达拉非的有效方法。     

HPLC法测定乙酰谷酰胺中异构体的含量

目的 建立高效液相色谱法测定乙酰谷酰胺中异构体N-乙酰-D-谷氨酰胺的含量测定方法。方法 采用高效液相色谱法,直链淀粉-三（S）-α-甲苯基氨基甲酸酯为填充剂（AS-H 4.6 mm×250 mm,5 μm）手性色谱柱;检测波长210 nm,柱温30 ℃,流动相为正己烷（每1 000 mL加0.5 mL三氟乙酸和0.5 mL三乙胺）：无水乙醇（每1 000 mL中加0.5 mL三氟乙酸和0.5 mL三乙胺）=90:10。结果 浓度在1.289 3~36.099 5 μg·ml^-1范围内线性关系良好（r=0.998 2,n=5）,平均回收率94.9%,RSD=1.6%（n=9）,方法的检测限LOD为0.314 6 μg·ml^-1,定量限1.258 4 μg·mL^-1。结论 所用方法专属性强、结果准确、稳定性好,适用于乙酰谷酰胺中异构体N-乙酰-D-谷氨酰胺的检测。     

儿童过敏性鼻炎治疗前后外周血CD4+CD25+CD127lo/-Treg细胞与炎症因子变化分析

目的 探讨儿童过敏性鼻炎（AR）治疗前后外周血CD4⁺CD25⁺CD127^lo/-Treg及白细胞介素2（IL-2）、肿瘤坏死因子α（TNF-α）、人转化生长因子β1（TGF-β1）的水平变化及临床意义。方法 将厦门长庚医院收治的108例AR患儿作为AR组,根据疾病严重程度分为轻度、中重度组,另采用单纯随机抽样法选取年龄、性别匹配的80例健康儿童作为对照组,检测两组对象入院时CD4⁺CD25⁺CD127^lo/-Treg、IL-2、TNF-α、TGF-β1水平;AR患者均给予对症治疗,检测治疗前、治疗1个月、治疗6个月CD4⁺CD25⁺CD127^lo/-Treg、IL-2、TNF-α、TGF-β1水平,采用Pearson相关分析疾病严重程度与外周血CD4⁺CD25⁺CD127^lo/-Treg的相关性及两者与IL-2、TNF-α、TGF-β1相关性。结果 AR患者CD4⁺CD25⁺CD127^lo/-Treg、IL-2、TGF-β1水平分别为（6.264±0.135）%、（50.16±11.67）ng/L、（14.21±5.34）ng/L,均低于对照组;TNF-α为（1.82±0.62）ng/L,高于对照组的（0.34±0.19）ng/L,差异均有统计学意义（P<0.05）。轻度AR患者CD4⁺CD25⁺CD127^lo/-Treg、IL-2、TGF-β1水平分别为（6.305±0.137）%、（59.34±13.05）ng/L、（16.97±4.69）ng/L,均高于中重度AR组患者,TNF-α水平为（1.64±0.57）ng/L,低于中重度AR组患者的（1.93±0.65）ng/L,差异均有统计学意义（P<0.05）。AR组治疗后第1、6个月CD4⁺CD25⁺CD127^lo/-Treg、IL-2、TGF-β1水平高于治疗前,TNF-α水平低于治疗前,差异均有统计学意义（P<0.05）。Pearson相关分析显示：外周血CD4⁺CD25⁺CD127^lo/-Treg、TNF-α与疾病严重程度呈正相关关系（r=0.681、0.581,P<0.05）,IL-2、TGF-β1与疾病严重程度呈负相关关系（r=-0.613、-0.579,P<0.05）;外周血CD4⁺CD25⁺CD127^lo/-Treg与IL-2、TGF-β1呈负相关性（r=-0.675、-0.691,P<0.05）,与TNF-α呈正相关关系（r=0.618,P<0.05）。结论 AR患者存在CD4⁺CD25⁺CD127^lo/-Treg及IL-2、TGF-β1下降,TNF-α上升,且与病情程度有关,治疗后均明显改善。     

阿托伐他汀的肝毒性机制研究

目的 研究阿托伐他汀肝毒性损伤作用及机制。方法 将24只Wistar han雄鼠分为对照组和阿托伐他汀低（68.5mg/kg）、高剂量组（205.5 mg/kg）,按照10 mL/kg的药液体积给药,溶媒对照组ig等体积5% CMC-Na,连续ig 28 d。检测血清中天门冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、碱性磷酸酶（ALP）、尿素氮（BUN）和血肌酐（CRE）的含量,HE染色观察肝组织病理。在体外,HepG2细胞经传代培养后,给予阿托伐他汀干预24 h,检测细胞存活率,丙二醛（MDA）水平、Na⁺-K⁺-ATP酶和Ca²⁺-Mg²⁺-ATP酶活性及线粒体膜电位。结果 与对照组比较,阿托伐他汀高剂量组大鼠肝细胞弥漫性肿胀,核分裂多见,部分肝细胞极性消失,排列紊乱（P<0.05）。与对照组比较,阿托伐他汀高剂量组给药后血清中ALT和AST显著升高（P<0.05、0.01）。在体外,与对照组比较,阿托伐他汀125、250、500 μmol/L能明显抑制细胞存活率（P<0.05、0.001）。与对照组比较,阿托伐他汀500 μmol/L HepG2细胞MDA含量明显升高（P<0.01）。与对照组比较,阿托伐他汀125 μmol/L能使Na⁺-K⁺-ATP酶活性增强,500 μmol/L使Na⁺-K⁺-ATP酶活性降低（P<0.001）。与对照组比较,阿托伐他汀125、250、500 μmol/L均能使能使Ca²⁺-Mg²⁺-ATP酶活性降低（P<0.01,0.001）。与对照组比较,阿托伐他汀125、250、500 μmol/L均能降低线粒体膜电位（P<0.001）。结论 阿托伐他汀高剂量可导致肝组织损伤,其毒性作用通过破坏细胞的线粒体膜电位,抑制Na⁺-K⁺-ATP酶、Ca²⁺-Mg²⁺-ATP酶活性,细胞膜脂质过氧化,从而破坏细胞内微环境的平衡,导致细胞凋亡和坏死。     

N6-苯甲酰基-2'-叔丁基二甲基硅氧基腺苷-3'-H-膦酸的合成工艺研究

目的 研究N~6-苯甲酰基-2′-叔丁基二甲基硅氧基腺苷-3′-H-膦酸的合成工艺。方法 以腺苷为起始原料,先对腺苷的嘌呤氨基进行苯甲酰基保护,再分别向腺苷的5′位和2′位引入二甲氧基三苯甲基(DMT)和叔丁基二甲基硅基(TBDMS)保护基,制备得到关键中间体N~6-苯甲酰基-5′-二甲氧基三苯甲氧基-2′-叔丁基二甲基硅氧基腺苷(3)。中间体3与磷试剂2-氯-4H-1,3,2-苯并二氧磷杂环己烷-4-酮反应引入膦酸基团,最后使用二氯乙酸脱除DMT保护基得到目标产物。结果 经过5步反应得到了目标化合物N~6-苯甲酰基-2′-叔丁基二甲基硅氧基腺苷-3′-H-膦酸,并利用~1H-NMR、~(31)P-NMR、质谱等方法确证了其结构。本合成工艺的总收率为35.7%,目标化合物的质量分数为98.5%。结论 该合成工艺与原有方法相比步骤短,操作简单,具有良好的应用前景。     

The anti-cancer agent SU4312 unexpectedly protects against MPP+-induced neurotoxicity via selective and direct inhibition of neuronal NOS

Background and Purpose

SU4312, a potent and selective inhibitor of VEGF receptor-2 (VEGFR-2), has been designed to treat cancer. Recent studies have suggested that SU4312 can also be useful in treating neurodegenerative disorders. In this study, we assessed neuroprotection by SU4312 against 1-methyl-4-phenylpyridinium ion (MPP⁺)-induced neurotoxicity and further explored the underlying mechanisms.

Experimental Approach

MPP⁺-treated neurons and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated zebrafish were used to study neuroprotection by SU4312. NOS activity was assayed in vitro to examine direct interactions between SU4312 and NOS isoforms.

Key Results

SU4312 unexpectedly prevented MPP⁺-induced neuronal apoptosis in vitro and decreased MPTP-induced loss of dopaminergic neurons, reduced expression of mRNA for tyrosine hydroxylase and impaired swimming behaviour in zebrafish. In contrast, PTK787/ZK222584, a well-studied VEGFR-2 inhibitor, failed to prevent neurotoxicity, suggesting that the neuroprotective actions of SU4312 were independent of its anti-angiogenic action. Furthermore, SU4312 exhibited non-competitive inhibition of purified neuronal NOS (nNOS) with an IC₅₀ value of 19.0 μM but showed little or no effects on inducible and endothelial NOS. Molecular docking simulations suggested an interaction between SU4312 and the haem group within the active centre of nNOS.

Conclusions and Implication

SU4312 exhibited neuroprotection against MPP⁺ at least partly via selective and direct inhibition of nNOS. Because SU4312 could reach the brain in rats, our study also offered a support for further development of SU4312 to treat neurodegenerative disorders, particularly those associated with NO-mediated neurotoxicity.     

The use and safety of doxycycline hyclate and other second-generation tetracyclines

Tetracyclines have long been used to treat a wide variety of medical conditions, especially in the field of dermatology. Unfortunately, safety concerns, especially gastrointestinal (GI), have always been present. Other safety concerns have included tooth development in children, candidiasis, vestibular concerns, photosensitivity/phototoxicity, and more unusual adverse effects such as uncontrolled hypertension. This article first discusses the pharmacological development of the tetracyclines from the first to the second generation versions with an emphasis on the safety concerns, especially with regards to doxycycline hyclate (DH). Second, the adverse effects of the tetracyclines are discussed. Third, the favorable side effect profile of DH delayed release capsules (Doryx^®) is compared with DH powder contained in tablets (Vibramycin^®). Fourth, the increased use with a continued favorable safety profile is also discussed concerning the subantimicrobial dosing of DH for acne. Fifth, the safety of periodontic uses of DH is discussed. Last, the favorable safety profiles of the 2006 approved uses of an anti-inflammatory dose of 40 mg doxycycline for rosacea and an extended-release minocycline tablet for acne are also discussed.     

Advances in nano-delivery systems for doxorubicin: an updated insight

Doxorubicin (DOX) is the most effective chemotherapeutic drug developed against broad range of cancers such as solid tumours, transplantable leukemias and lymphomas. Conventional DOX-induced cardiotoxicity has limited its use. FDA approved drugs i.e. non-pegylated liposomal (Myocet^®) and pegylated liposomal (Doxil^®) formulations have no doubt shown comparatively reduced cardiotoxicity, but has raised new toxicity issues. The entrapment of DOX in biocompatible, biodegradable and safe nano delivery systems can prevent its degradation in circulation minimising its toxicity with increased half-life, enhanced pharmacokinetic profile leading to improved patient compliance. In addition, nano delivery systems can actively and passively target the tumour resulting increase in therapeutic index and decreased side effects of drug. Foreseeing the need of a comprehensive review on DOX nanoformulations, in this article we for the first time have given an updated insight on DOX nano delivery systems.     

2',4'-二羟基-3'-甲基-3-甲氧基查耳酮上调p21抑制人肝癌HepG2细胞的生长

目的 探讨2'',4''-二羟基-3''-甲基-3-甲氧基查耳酮(C20)对人肝癌HepG2细胞的体外抗肿瘤作用及其潜在的作用机制。方法 通过CCK-8法、集落形成实验、5-乙炔基-2''-脱氧尿苷(EdU)染色法检测C20对人肝癌HepG2细胞增殖的影响;通过彗星实验检测C20(10 μmol·L^-1)对HepG2细胞DNA损伤的影响;通过流式细胞术检测C20(5、10 μmol·L^-1)对HepG2细胞周期阻滞的影响;通过Hoechst染色和流式细胞术检测C20(5、10 μmol·L^-1)对HepG2细胞凋亡的影响。借助Western blotting法检测C20(5、10 μmol·L^-1)处理对HepG2细胞中与凋亡、DNA损伤、细胞周期阻滞相关蛋白表达水平的调控作用。结果 与对照组比较,C20显著抑制HepG2细胞的活力(P<0.001),给药48 h的半数抑制浓度(IC₅₀)为7.937 μmol·L^-1;5 μmol·L^-1 C20能够显著抑制HepG2细胞的集落形成能力(P<0.01);EdU染色结果显示5、10 μmol·L^-1的C20能够抑制人肝癌HepG2细胞的增殖能力;5、10 μmol·L^-1的C20显著诱导HepG2细胞G₂/M期阻滞(P<0.001);5、10 μmol·L^-1的C20显著促进HepG2细胞凋亡(P<0.001),并显著上调Caspas-3、Caspase-9以及PARP的剪切水平(P<0.01);10 μmol·L^-1的C20能够诱导HepG2细胞发生DNA损伤,并且5、10 μmol·L^-1的C20显著上调γH2AX、p21的蛋白水平(P<0.01)。结论 C20能够造成HepG2细胞发生DNA损伤,上调p21蛋白水平,导致细胞G₂/M期阻滞,并进一步诱发凋亡,发挥体外抗肝癌作用。     

Symptom-relieving and neuroprotective effects of the phytocannabinoid Δ⁹-THCV in animal models of Parkinson's disease

BACKGROUND AND PURPOSE

Previous findings have indicated that a cannabinoid, such as Δ⁹-THCV, which has antioxidant properties and the ability to activate CB₂ receptors but to block CB₁, might be a promising therapy for alleviating symptoms and delaying neurodegeneration in Parkinson''s disease (PD).

EXPERIMENTAL APPROACH

The ability of Δ⁹-THCV to reduce motor inhibition and provide neuroprotection was investigated in rats lesioned with 6-hydroxydopamine and in mice lesioned with lipopolysaccharide (LPS).

KEY RESULTS

Acute administration of Δ⁹-THCV attenuated the motor inhibition caused by 6-hydroxydopamine, presumably through changes in glutamatergic transmission. Moreover, chronic administration of Δ⁹-THCV attenuated the loss of tyrosine hydroxylase–positive neurones caused by 6-hydroxydopamine in the substantia nigra, through an effect related to its antioxidant properties (it was reproduced by cannabidiol -enriched botanical extract). In addition, CB₂ receptor–deficient mice responded to 6-hydroxydopamine in a similar manner to wild-type animals, and CB₂ receptors were poorly up-regulated in the rat substantia nigra in response to 6-hydroxydopamine. By contrast, the substantia nigra of mice that had been injected with LPS exhibited a greater up-regulation of CB₂ receptors. In these animals, Δ⁹-THCV also caused preservation of tyrosine hydroxylase–positive neurones. This effect probably involved CB₂ receptors as it was also elicited by the selective CB₂ receptor agonist, HU-308, and CB₂ receptor–deficient mice were more vulnerable to LPS lesions.

CONCLUSIONS AND IMPLICATIONS

Given its antioxidant properties and its ability to activate CB₂ but to block CB₁ receptors, Δ⁹-THCV has a promising pharmacological profile for delaying disease progression in PD and also for ameliorating parkinsonian symptoms.

LINKED ARTICLES

This article is part of a themed issue on Cannabinoids in Biology and Medicine. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2011.163.issue-7     

Evodiamine improves congnitive abilities in SAMP8 and APP(swe)/PS1(ΔE9) transgenic mouse models of Alzheimer's disease

Aim:

To investigate the effect of evodiamine (a quinolone alkaloid from the fruit of Evodia rutaecarpa) on the progression of Alzheimer''s disease in SAMP8 and APP^swe/PS1^ΔE9 transgenic mouse models.

Methods:

The mice at age of 5 months were randomized into the model group, two evodiamine (50 mg·kg⁻¹·d⁻¹ and 100 mg·kg⁻¹·d⁻¹) groups and an Aricept (2 mg·kg⁻¹·d⁻¹) group. The littermates of no-transgenic mice and senescence accelerated mouse/resistance 1 mice (SAMR1) were used as controls. After 4 weeks of treatment, learning abilities and memory were assessed using Morris water-maze test, and glucose uptake by the brain was detected using positron emission tomography/computed tomography (PET/CT). Expression levels of IL-1β, IL-6, and TNF-α in brain tissues were detected using ELISA. Expression of COX-2 protein was determined using Western blot.

Results:

In Morris water-maze test, evodiamine (100 mg·kg⁻¹·d⁻¹) significantly alleviated the impairments of learning ability and memory. Evodiamine (100 mg·kg⁻¹·d⁻¹) also reversed the inhibition of glucose uptake due to development of Alzheimer''s disease traits in mice. Furthermore, the dose of evodiamine significantly decreased the expression of IL-1β, IL-6, TNF-α, and COX-2 that were involved in the inflammation due to Alzheimer''s disease.

Conclusion:

The results indicate that evodiamine (100 mg·kg⁻¹·d⁻¹) improves cognitive abilities in the transgenic models of Alzheimer''s disease.     

Recent progress in the development of docetaxel and paclitaxel analogues

Docetaxel (Taxotere^®, Sanofi-Aventis) and paclitaxel (Taxol^®, Bristol-Myers Squibb) are potent anticancer agents commonly used for the treatment of breast, ovarian and other cancers. Chemotherapy with these compounds gives undesirable side effects due to their low solubility and to the lack of selectivity for cancer cells. Studies have been performed to solve these problems and to find more potent taxoids on drug-resistant cancers. This review summarises the progress in these areas as reported in recent patent applications on docetaxel and paclitaxel analogues that have been published between January 2003 and December 2005. The review specifically focuses on new methods for the production of taxoids, new potent analogues, including taxoid conjugates with improved solubility, tumour targeting taxoids and prodrugs, combinations with new anticancer agents and taxoid formulation and delivery.     

Characterization of histamine H3 receptors in Alzheimer's Disease brain and amyloid over-expressing TASTPM mice

Background and purpose:

Histamine H₃ receptor antagonists are currently being evaluated for their potential use in a number of central nervous system disorders including Alzheimer''s Disease (AD). To date, little is known about the state of H₃ receptors in AD.

Experimental approach:

In the present study we used the radiolabelled H₃ receptor antagonist [³H]GSK189254 to investigate H₃ receptor binding in the amyloid over-expressing double mutant APPswe × PSI.MI46V (TASTPM) transgenic mouse model of AD and in post-mortem human AD brain samples.

Key results:

No significant differences in specific H₃ receptor binding were observed between wild type and TASTPM mice in the cortex, hippocampus or hypothalamus. Specific [³H]GSK189254 binding was detected in sections of human medial frontal cortex from AD brains of varying disease severity (Braak stages I–VI). With more quantitative analysis in a larger cohort, we observed that H₃ receptor densities were not significantly different between AD and age-matched control brains in both frontal and temporal cortical regions. However, within the AD group, [³H]GSK189254 binding density in frontal cortex was higher in individuals with more severe dementia prior to death.

Conclusions and implications:

The maintenance of H₃ receptor integrity observed in the various stages of AD in this study is important, given the potential use of H₃ antagonists as a novel therapeutic approach for the symptomatic treatment of AD.     

RP-HPLC测定4，5，2’-三吗啉酰氧基-2，5'-二氯二苯甲酮原料药的含量及有关物质

目的 建立测定原料药4,5,2''-三吗啉酰氧基-2,5''-二氯二苯甲酮（LF1）的含量及有关物质的RP-HPLC方法。方法 采用Diamonsil C₁₈（250 mm×4.6 mm,5 μm）色谱柱,乙腈-磷酸水（60：40,pH3.0）为流动相,检测波长230 nm,体积流量1 mL/min,柱温25℃。结果 主峰与杂质峰分离良好,LF1和杂质A分别在质量浓度1.0~100（r=0.999 8）和0.2~2.4 mg/L （r=0.999 6）线性关系良好,最低检测限分别为1和2 ng/mL,平均回收率分别为100.7%和102.0%。结论 本法简便、快速、准确,可用于LF1原料药的含量及有关物质的测定。