外源性一氧化氮对大鼠抗氧化酶活性的影响

本研究利用亚硝基铁氰化钠作为体外一氧化氮（ＮＯ）前体，研究ＮＯ对大鼠肝Ｓ９中超氧化物岐化酶（ＳＯＤ），过氧化氢酶（ＣＡＴ）、谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）等抗氧化物酶的活性及脂质过氧化（ＬＰＯ）的影响。结果表明：外源性ＮＯ能体外抑制ＣＡＴ和ＳＯＤ活性，并能引起明显的ＬＰＯ，但对ＧＳＨ－Ｐｘ的活性无明显影响。     

QK—全科广谱治疗仪对冠心病病人血液对氧化反应及红细胞变形？…

本实验测了３５例冠心病病人使用ＱＫ－全科广谱仪治疗前后血中红细胞超氧化物歧化酶（ＯＳＤ）活力;全血谷胱苷肽过氧化物酶（ＧＳＨ－Ｐｘ）,过氧化氢酶（ＣＡＴ）活力;血浆总抗氧化能力（ＡＯＡ）;红细胞膜丙二醛（ＭＤＡ）含量;红细胞滤过指数（ＩＦ）的变化。结果治疗全血ＧＳＨ－Ｐｘ、ＣＡＴ活力、血浆ＡＯＡ明显下降,红细胞膜ＭＤＡ含量明显升高,红细胞ＩＦ明显升高,后与治疗前比较,全血ＧＳＨ－Ｐｘ,ＣＡＴ活力及     

银杏叶制剂对心绞痛患者的抗氧化和抗脂质过氧化作用

目的：探讨银杏叶制剂对心绞痛患者的抗氧化和抗脂质过氧化作用。方法：检测了７８例心绞痛患者经银杏叶制剂“天宝宁”治疗前后的血浆维生素Ｃ（Ｐ－ＶＣ）、维生素Ｅ（Ｐ－ＶＥ）、β－胡萝卜素（Ｐ－β－ＣＡＲ）、过氧化脂质（Ｐ－ＬＰＯ）以及红细胞超氧化物歧化酶（Ｅ－ＳＯＤ）、过氧化氢酶（Ｅ－ＣＡＴ）、谷胱甘肽过氧化物酶（Ｅ－ＧＳＨ－ＰＸ）、过氧化脂质（Ｅ－ＬＰＯ）值。结果：与治疗前比较,治疗后的Ｐ－ＶＣ、Ｐ－     

吸烟对慢性阻塞性肺疾病脂质过氧化系统及α1—抗胰蛋白酶的影响

吸烟对慢性阻塞性肺疾病（ＣＯＰＤ）患者体内自由基水平和α１－抗胰蛋白酶的影响。采用硫代巴比妥法、放射免疫法和酶标法对３５例吸烟和２５例非吸烟ＣＯＰＤ患者血清脂质过氧化物（ＬＰＯ）、超氧化物歧化酶ＳＯＤ）、α１－ＡＴ和α１－酸性糖蛋白（α１－ＡＧ）进行测定。结果显示：吸烟ＣＯＰＤ组血中ＬＰＯ、α１－ＡＧ明显高于非吸烟组，ＳＯＤ、α１０－ＡＴ明显低于非吸烟组；吸烟组ＬＰＯ和α１－ＡＴ呈负相关，ＳＯＤ和     

UBIO治疗贝赫切特综合征疗效动态观察

采用紫外线辐射充氧治疗２２例贝赫切 综合征病人，并动态观察了其治疗前后血流变学、ＳＯＤ、ＧＳＨ－ＰＸ、ＬＰＯ、ＭＤＡ、ＣＡＴ、ＴＮＦ以及白细胞亚微结构的变化，以药物治疗的１１例ＢＳ病人做对照组。结果显示：ＢＳ病人经治疗后，其全血，血浆粘度，ＬＰＯ、ＭＤＡ、ＴＮＦ均显著降低，而ＳＯＤ、ＧＳＨ－ＰＸ、ＣＡＴ显著升高，ＵＢＩ组变化程度较药物组更为明显。ＵＢＩＯ治疗后白细胞表面微绒毛普遍增多，变粗，其细胞     

睡眠呼吸暂停与脂持代谢紊乱

对５８例有或无睡眠呼吸暂停综合症（ＳＡＳ）患者的血脂测定结果显示：β－ＬＰ、ＴＣ、ＴＧ、ＬＤＬ、ＶＬＤＬ和ＡｐｏＢ均较对照组升高（Ｐ均〈０．０１），ＨＤＬ和ＡｐｏＡ下降（Ｐ均〈０．０５）。各项指标与ＳＡＳ年限无关，而与呼吸暂停次数、时间和ＳａＯ２相关。除ＨＤＬ和ＡｐｏＡ呈负相关，其它各项指标均呈正相关。提示ＳＡＳ患者也有脂质代谢异常存在。     

甘草对老年大鼠CAT,GSH—Px,LPO影响的实验研究

本实验以Ｗｉｓｔａｒ大鼠为研究对象,对大鼠红细胞ＣＡＴ（过氧化氢酶）活性,全血ＧＳＨ－Ｐｘ（谷胱甘肽过氧化物酶）活性,血浆ＬＰＯ（过氧化脂质）进行测定。观察上述指标的随龄变化,甘草对老年大鼠体内上述指标的影响。结果表明,大鼠体内的抗氧化酶ＣＡＴ,ＧＳＨ－Ｐｘ活性在其成长阶段随年龄上升（Ｐ〈０．０１）,在衰老阶段随龄下降（Ｐ〈０．０１）。自由基代谢产物ＬＰＯ含量在血浆中随龄增加（Ｐ〈０．０１）甘草水     

褪黑素抗自由基作用及其机制

目的研究褪黑素（ＭＥＬ）的抗自由基作用,并探讨其作用机制。方法以丙二醛（ＭＤＡ）为指标,考察ＭＥＬ对四氯化碳（ＣＣｌ４）或氰化钾（ＫＣＮ）处理小鼠肝或脑组织脂质的保护作用;考察ＭＥＬ对环磷酰胺所致小鼠骨髓细胞微核的影响;观察ＭＥＬ清除羟自由基（·ＯＨ）作用,及对醋氨酚处理小鼠肝谷胱甘肽（ＧＳＨ）含量和大鼠红细胞超氧化物歧化酶（ＳＯＤ）、过氧化氢酶（ＣＡＴ）和全血谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）的影响。结果ＭＥＬ（２．０,１０．０ｍｇ·ｋｇ－１,ｉｐ）能显著对抗ＣＣｌ４或ＫＣＮ所致小鼠肝脏或脑组织丙二醛含量的增加。ＭＥＬ（１０．０ｍｇ·ｋｇ－１,ｉｐ）可明显抑制环磷酰胺引起的小鼠骨髓细胞微核增多。ＭＥＬ（０．０７８～５．０ｍｍｏｌ·Ｌ－１）可直接清除·ＯＨ。ＭＥＬ（１．０,１０．０ｍｇ·ｋｇ－１,ｉｐ）可显著对抗醋氨酚（ＡＡＰ）所致小鼠ＧＳＨ的耗竭作用。ＭＥＬ（１．０,５．０ｍｇ·ｋｇ－１,ｉｐ）亦可显著提高大鼠红细胞内ＳＯＤ、ＣＡＴ、全血ＧＳＨ－Ｐｘ活性。结论ＭＥＬ可保护脂质和核酸免受过氧化损伤,这可能与其直接清除·ＯＨ,提高机体ＧＳＨ含量及增强ＳＯＤ、ＣＡＴ、ＧＳＨ－Ｐｘ活力有关。     

硒多糖、亚砷酸钠对大鼠肝微粒体酶和GSH-Px等的影响

研究了硒多糖、亚砷酸钠在体内、外对大鼠肝微粒体酶细胞色素Ｐ－４５０、ｂ５、ＮＡＤ（Ｐ）Ｈ－细胞色素Ｃ还原酶、谷胱甘肽硫转移酶（ＧＳＴ）的影响;并通过测定硒多糖、亚砷酸钠对肝谷胱甘肽过氧化物酶（ＧＳＨ－Ｐｘ）和脂质过氧化（ＬＰＯ）的影响,探讨了硒、砷相互作用的机理。结果表明：连续７天腹腔注射０．２ｍｇ／ｋｇ硒多糖,细胞色素Ｐ－４５０、ｂ５的含量、ＧＳＴ的活性降低（Ｐ＜０．０５）;硒多糖明显诱导ＧＳＨ－Ｐｘ的活性,降低脂质过氧化,拮抗亚砷酸钠对ＬＰＯ的作用。亚砷酸钠显著增强肝细胞脂质过氧化（Ｐ＜０．０５）,对ＧＳＨ－Ｐｘ和肝微粒体酶无明显影响     

丹皮总甙对化学性肝损伤保护作用机制

目的 研究丹皮总苷（ＴＧＭ）对ＣＣｌ４和Ｄ－Ｇａｌ－Ｎ致小鼠化学性肝损伤的保护作用机制。方法 采用ＣＣｌ４和Ｄ－Ｇａｌ－Ｎ所致小鼠化学性肝损伤模型进行研究,用ＴＢＡ法和ＤＴＮＢ法测定ＭＤＡ和ＧＳＨ－Ｐｘ。结果 ＴＧＭ具有促进肝脏糖原合成和提高血清蛋白含量的作用（Ｐ〈０．０１）,可明显降低肝匀浆脂质过氧化产物丙二醛（ＭＤＡ）的含量（Ｐ〈０．０１）及提高血清和肝脏谷胱甘肽过氧化物酶活力（Ｐ〈０．０１）     

Assessment of dose proportionality of muraglitazar after repeated oral dosing in rats via a sparse sampling methodology

Muraglitazar is an alpha/gamma-dual peroxisome proliferator-activated receptor (PPAR) agonist. This study evaluated the single- and multiple-dose oral toxicokinetics of muraglitazar in rats at doses of 3, 30 and 300 mg/kg/day. In total, 15 rats/gender/dose group received muraglitazar every day for 1 month. On both day 1 and day 28, blood samples were obtained at 0.5, 2, 4, 6, 8 and 24 h post-dose, followed by LC/MS analysis. In order to minimize blood loss in the rats, a sparse sampling approach was used to delineate the toxicokinetics.The peak plasma concentration (C(max)) and area under the plasma concentration-time curve (TAUC(0-t)) values for muraglitazar increased in a proportion less than the increment in dose. As the dose increased in the ratio 1:10:100, the C(max) for muraglitazar in male and female rats increased in the ratio of 1:10.3:58.6 and 1:15.3:75.3 on day 1, and 1:5.9:28.1 and 1:13.3:37.3 on day 28, respectively. The corresponding TAUC(0-t) values for males and females were in the ratio of 1:10.2:131 and 1:12.4:131 on day 1, and 1:9.5:93.4 and 1:11.8:94.3 on day 28, respectively. The results indicate that muraglitazar exhibits a dose dependent toxicokinetics in rats and the systemic exposure of muraglitazar was decreased on day 28 compared with day 1.     

氟伏沙明在小鼠体内抗抑郁作用的时辰药理学及其机制研究

目的:研究氟伏沙明在小鼠体内抗抑郁作用的时辰药理学及其可能机制。方法:以生理盐水为对照组,考察相邻2天的9:00、13:00、17:00、21:00、1:00、5:00共6个时间点注射氟伏沙明(30mg.kg-1)对小鼠在水中5min内的不动累积时间的影响,和同日内明、暗期(9:00、21:00)注射氟伏沙明对小鼠在暗箱中10min自发性活动(运动距离、运动时间、静止时间)的影响;另外还检测正常小鼠同日内明、暗期(9:00、21:00)脑组织中5羟色胺(5-HT)转运体(SERT)mRNA表达、5-HT再摄取浓度、sigma-1受体的变化。结果:与对照组比较,氟伏沙明能显著缩短小鼠的不动累积时间(P<0.01),其中21:00组不动累积时间最低,但不影响小鼠自发性活动;与明期(9:00)组比较,正常小鼠暗期(21:00)组脑组织中SERTmRNA表达和5-HT再摄取浓度及sigma-1受体的表达均明显升高(P<0.05)。结论:氟伏沙明在小鼠体内的抑郁作用具有昼夜节律性,该作用可能与中脑SERTmRNA的表达、sigma-1受体表达的昼夜节律变化相关。     

Efficacy and safety of a fixed dose combination tablet of asunaprevir + beclabuvir + daclatasvir for the treatment of Hepatitis C

ABSTRACT

Introduction: Hepatitis C virus (HCV) is estimated to infect approximately 70 million people worldwide. If left untreated, chronic infection can progress to cirrhosis, liver failure or hepatocellular carcinoma. The advent of new direct-acting antivirals (DAA) has revolutionized patients’ chances of treatment and viral elimination. Currently, several DAA options are available on the market.

Areas covered: This review focuses on the pharmacokinetics, efficacy, tolerability and safety profile of DCV-TRIO, a twice-daily fixed-dose combination of daclatasvir, asunaprevir and beclabuvir approved in Japan for the treatment of genotype 1 HCV infection.

Expert opinion: The DCV-TRIO combination achieved good response rates in genotype 1 patients (SVR12 ≥ 95% in naïve subtype 1b), independently from IL28B genotype, cirrhotic status and prior interferon exposure. On the other hand, unsatisfying response rates were reported in DAA-experienced patients and the risk of RAS selection should not be underestimated. Moreover, DCV-TRIO lacks differentiation from its earlier-launched DAA rivals, presents an inconvenient twice-daily dosing schedule and is not recommended in patients with advanced liver and kidney disease. All these drawbacks considerably limit its effective commercial potential. However, it can be a therapeutic option against HCV in tailored approaches according to the needs of different markets across the world.

Abbreviations AE: adverse event; ALT: alanine aminotransferase; AST: aspartate aminotransferase; ASV: asunaprevir; AUC: area under the curve; BCRP: Breast Cancer Resistance Protein; BCV: boceprevir; BID: bis in die; CI: confidence intervals; CLcr: creatinine clearance; DAA: direct acting antivirals; DCV: daclatasvir; EC50: Half maximal effective concentration; GT: genotype; HCV: Hepatitis C virus; IFN: Interferon; NHL: non-Hodgkin lymphoma; OATP: Organic anion transporting polypeptides; OR: odds ratio; P-gp: P-glycoprotein; PK: pharmacokinetics; QD: quo die; RAS: resistance-associated substitutions; SVR: sustained virological response; USD: Unites States dollar     

不同配比头孢呋辛/三唑巴坦的体外抗菌活性研究

目的 评价不同配比头孢呋辛/三唑巴坦(CXM/TB)的体外抗菌活性.方法 采用平皿琼脂二倍稀释法测定不同配比CXM/TB对1436株临床分离致病菌的最低抑菌浓度(MIC).结果 不同配比CXM/TB(1:1、2:1、3:1、4:1、8:1和16:1)对1436株临床分离菌具有广谱抗菌作用,CXM/TB 1:1、2:1、3:1的抗菌活性相近,稍强于CXM/TB 4:1、8:1、16:1.不同配比CXM/TB对1109株产β-内酰胺酶菌株中的金葡菌、表皮葡萄球菌、大肠埃希菌、肺炎克雷伯菌、醋酸钙不动杆菌、普通变形菌、奇异变形菌、雷氏普罗威登斯菌、摩氏摩根菌、阴沟肠杆菌、产气肠杆菌、异型柠檬酸杆菌和黏质沙雷菌的MIC_(90)值分别为CXM的1/4～1/32,对产ESBLs大肠埃希菌、肺炎克雷伯菌的MIC_(90)值分别为CXM的1/8～1/16,但对产β-内酰胺酶的铜绿假单胞菌、假单胞菌属(除铜绿假单胞菌)的MIC_(90)值与CXM相近;对不产β-内酰胺酶的金葡菌、表皮葡萄球菌、化脓链球菌、肺炎链球菌、流感嗜血菌、副流感嗜血菌的抗菌活性与CXM相近.不同配比CXM/TB对612株产酶耐药临床分离菌中的金葡菌、表皮葡萄球菌、大肠埃希菌、肺炎克雷伯菌、醋酸钙不动杆菌、普通变形菌、奇异变形菌、产气肠杆菌的MIC_(90)分别为CXM的1/8～1/64.不同配比CXM/TB对MRSA、MRSE、粪肠球菌、假单胞菌属的抗菌活性差.结论 不同配比CXM/TB均有较强的体外抗菌活性,CXM/TB 1:1、2:1、3:1的抗菌活性相近,稍优于CXM/TB 4:1、8:1、16:1,TB增强了CXM抗产β-内酰胺酶细菌的活性.     

Investigating displacement effects as a result of the Sydney,NSW alcohol lockout legislation

Aims: On 30 January 2014, in efforts to reduce alcohol-related violence, the New South Wales Parliament adopted alcohol lockout legislation targeting a geographically defined area: the Sydney entertainment precinct. This study used qualitative methods to explore with stakeholders of two areas (Kings Cross/Potts Point and Newtown) whether there was any evidence of displacement of alcohol-related problems from inside to outside the lockout zone.

Methods: Four focus groups were conducted in mid-2015 with residents and patrons: two in Kings Cross/Potts Point (where the measures were implemented) and two in Newtown (an alternative entertainment precinct exempt from the measures). Each explored experiences pre and post lockouts and any perceived changes in the number of people in the area, level of disorderly conduct, patterns of drug and alcohol consumption, public amenity and public safety.

Findings: Stakeholders in Kings Cross/Potts Point reported many improvements since the reforms: including reduced patron numbers, less waste and improved public amenity. However, stakeholders from Newtown reported the opposite: increased patron numbers, reduced public amenity and reduced public safety.

Conclusions: This provides tentative evidence that even if the Sydney lockouts have reduced alcohol-related violence there may have been a partial displacement of alcohol-related problems to outside the lockout zone.     

Circadian variation in methamphetamine- and apomorphine-induced increase in ambulatory activity in mice

The existence of circadian variation in methamphetamine- and apomorphine-induced change in ambulatory activity in mice was investigated. Adult male mice of dd strain, which had been housed on a 12 hr light-dark schedule (light period; 6:00–18:00) for 4 weeks, received injections of either methamphetamine HCl 1 or 2 mg/kg SC at one of six times of day (3:00, 7:00, 11:00, 15:00, 19:00 and 23:00), or apomorphine HCl 0.5 or 1 mg/kg SC at one of six times of day (3:30, 7:30, 11:30, 15:30, 19:30 and 23:30). The control animals were administered a physiological saline vehicle alone at the corresponding times of day. The ambulatory activity of each mouse was measured by a tilting-type activity cage for 3 hr after methamphetamine, and for 1 hr after apomorphine. A circadian variation in the ambulatory activity was observed after the administration of the saline, methamphetamine and apomorphine. Here, the highest activity counts were found when the saline, methamphetamine and apomorphine were administered during the late dark period (3:00 or 3:30), while the lowest activity counts were found when the saline and apomorphine 1 mg/kg were administered during the mid light period (11:00 or 11:30), and methamphetamine 1 and 2 mg/kg and apomorphine 1 mg/kg were administered during the late light period (15:00 or 15:30). The circadian variation in methamphetamine-induced increase in the activity was abolished by a pretreatment with reserpine 2 mg/kg SC 4 hr before, but that of apomorphine was maintained even by the pretreatment with reserpine. The present results suggest that the methamphetamine- and apomorphine-induced increase in the ambulatory activity in mice is dependent on the time-of-day 3f the drug administration, and the occurence is mainly due to a circadian variation in activity of the catecholaminergic systems in the brain.     

不同训练时段影响甲基苯丙胺诱导的大鼠自身给药行为的形成

目的 观察不同时间给予甲基苯丙胺(METH)对大鼠形成自身给药行为的影响。方法 通过6 d的FR1程序训练合格的大鼠进入实验。按照4个给药时间8:00-8:30,10:00-10:30,11:30-12:00及16:00-16:30和2个给药因素生理盐水和METH 0.05 mg·kg^-1分为8组,持续8 d。在自身给药装置中FR1程序记录给药次数和有效鼻触和无效鼻触次数。结果 与同一给药时间的溶剂对照组相比,METH组大鼠自身给药的次数及有效鼻触次数显著增加(P<0.05)。不同时间段给予METH组的给药次数和有效鼻触次数均没有显著性差异,但是从8 d的给药次数来看,分别为8:00-8:30组(86.2±23.8)<10:00-10:30组(104.3±41.3)<11:30-12:00组(123.4±50.3)<16:00-16:30组(155.0±51.7)。从前4 d给药时间8:00-8:30改为后4 d给药时间11:30-12:00后,给药次数和有效鼻触次数明显增加(P<0.05);从前4 d给药时间11:30-12:00改为后4 d给药时间8:00-8:30后,给药次数和有效鼻触次数明显减少(P<0.05)。8组大鼠间无效鼻触次数没有显著差异。结论 10:00-17:00时间段进行训练有利于大鼠自身给药行为的形成。     

Clinical translation of immunoliposomes for cancer therapy: recent perspectives

Introduction: Liposomes have been extensively investigated as drug delivery vehicles. Immunoliposomes (ILs) are antibody-conjugated liposomes designed to selectively target antigen-expressing cells. ILs can be used to deliver drugs to tumor cells for improving efficacy and reducing toxicity. In addition, ILs can be used in immunoassays, immunotherapy, and imaging. Although there has been extensive coverage on ILs in the literature, only a limited number of clinical trials have been reported and no IL drug has been approved by the FDA.

Areas covered: Factors to consider in developing ILs are discussed, including the choice of antibody or antibody fragment, the formulation of liposomes, and the conjugation chemistry. In addition, challenges and opportunities in clinical development of ILs are discussed. The purpose of this review is to provide an overview on the state of the art of ILs and to discuss potential future developments.

Expert opinion: IL research has had a lengthy history and numerous preclinical studies have yielded encouraging results. However, there are a number of obstacles to clinical translation of ILs. Given the unique capabilities of ILs, its potential for clinical application is underexplored. There is great potential for expanded role for ILs in the clinic and further efforts to this end are warranted.

Abbreviations: Ab: antibody; ADCs: antibody-drug conjugates; API: active pharmaceutical ingredient; ADCC: antibody-dependent cellular cytotoxicity; CR: complete remission; cGMP: current good manufacturing practice; DSPE: distearoyl phosphatidylethanolamine; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; EPR: enhanced permeability and retention; Fc: fragment crystalline; Tf: transferrin; HACA: human-anti-chimeric antibody; HAHA: human-anti-human antibody; HAMA: human-anti-mouse antibody; HER2: human epidermal growth factor 2; IL: immunoliposome; LNPs: lipid nanoparticles; MRI: magnetic resonance imaging; MTD: maximum tolerated dose; PEG: polyethylene glycol; PET: positron emission tomography; PR: partial response; PSMA: prostate-specific membrane antigen; scFv: single-chain variable fragment; SPECT: single photon emission computed tomography; TTR: transthyretin     

Airborne particulate matter impairs corneal epithelial cells migration via disturbing FAK/RhoA signaling pathway and cytoskeleton organization

Background: Cornea is the outmost structure of the eye and exposed directly to the air pollution. However, little is known about the effect of PM2.5 on corneal epithelium, which is critical for maintenance of cornea homeostasis and visual function.

Objective: We investigated the influence of PM2.5 exposure on corneal epithelial migration and the possible mechanisms involved in the process.

Methods: We observed wound healing in mouse model of cornea abrasion, evaluated the migration and mobility of cultured corneal epithelial cells with wound scratch assay and Transwell migration assay, detected the phosphorylation and interaction of FAK/paxillin with immunofluorescence and immunoprecipitation, and determined the RhoA activity and actin reorganization, in response to PM2.5 exposure.

Results: Exposure to PM2.5 remarkably inhibited corneal epithelial cell migration both in mouse model of corneal abrasion and in cell culture model. We found the phosphorylation and interaction of FAK/paxillin, RhoA activity as well as actin reorganization were suppressed by PM2.5 exposure. Moreover, formation of ROS might play a role in the action of PM2.5.

Conclusions: PM2.5 exposure could result in delay of corneal epithelium wound healing by inhibiting cell migration, thus more attention should be paid to the potential risk of corneal infection and effort should be made to protect eyes against impairment induced by PM2.5