硒和/或维生素E对实验性高脂血症大鼠心、肝、肾及血清中一氧化氮及一氧化氮合酶的影响

目的 :观察硒和/或维生素E(VE)对实验性高脂血症大鼠心、肝、肾、血清一氧化氮 (NO)及一氧化氮合酶 (NOS)的影响。方法 :对大鼠喂以高脂饲料致实验性高脂血症 ,然后分别分组给予硒和/或VE ,4wk后取血及心、肝、肾组织匀浆 ,采用硝酸还原酶等方法测定上述组织的NO和NOS含量。结果 :高脂饲料可致血清、心、肝、肾组织中NO含量及NOS活性降低 ;硒和/或VE能不同程度地增加这些组织中NO含量及心、肝、肾中的NOS活性 (P<0 05或P<0 01) ,且两者合用比单用作用更明显。结论 :硒和/或VE可致实验性高脂血症大鼠心、肝、肾及血清中的NO和NOS发生改变。     

荞麦种子总黄酮降血脂、血糖及抗脂质过氧化作用的研究

目的　研究荞麦种子总黄酮降血糖、血脂及抗脂质过氧化作用并探讨其作用机制。方法　以高胆固醇、高脂饲料诱发高脂模型大鼠 ,四氧嘧啶致糖尿病小鼠 ,应用荞麦种子总黄酮 (TFB)治疗 10d ,检测空腹血糖 (FBG)、血清胆固醇(TC)、甘油三酯 (TG)、胰岛素 (INS)、C肽 (C P)及血清和肝组织脂质过氧化产物丙二醛 (MDA)水平。结果　TFB具有抑制高脂血症大鼠TC、TG、FBG的升高和肝脂质过氧化作用 (P <0 0 5 ) ,可使糖尿病小鼠FBG降低 ,改善糖耐量(OGTT) ,对血浆INS和C P无影响 ,但胰岛素敏感指数(ISI)明显高于实验对照组 (P <0 0 5 )。结论　TFB具有降血糖、降血脂、增加机体对胰岛素敏感性和抗脂质过氧化作用     

高胆固醇血症家兔NO合成酶抑制物含量与脂质过氧化的关系(英文)

目的:探讨高脂饲养家兔血中NO合成酶抑制物二甲基精氨酸(DMA)含量变化与脂质过氧化的关系。方法:检测高脂饲养家兔血清总胆固醇、甘油三脂、丙二醛(MDA)及DMA含量,并观察离体胸主动脉内皮依赖性舒张反应。结果:高脂饲养家兔血脂、血清MDA和DMA含量比正常组增加(MDA为2.88±s0.20vs1.54±0.13nmol·L~(-1),P<0.01,DMA为1.51±0.07vs0.75±0.13μmol·L~(-1),P<0.01),胸主动脉舒张反应降低(最大舒张％为45.59±3.1vs76.93±5.68％)。维生素E抑制MDA升高的同时降低DMA含量及改善内皮舒张功能。结论:高脂血症家兔血清DMA含量的升高可能与脂质过氧化的增加有关。     

乌贼墨对高脂血症大鼠血脂代谢和抗氧化能力的影响

目的 探讨乌贼墨对实验性高脂血症大鼠血脂代谢和抗氧化能力的影响。方法 饲喂高脂饲料建立高脂血症大鼠模型，同时灌胃乌贼墨，剂量分别为50和200mg·kg^-1，连续30d。分别测定大鼠血清总胆固醇（TC），甘油三酯（TG），低密度脂蛋白胆固醇（LDL—c），高密度脂蛋白胆固醇（HDL-c）和一氧化氮（NO）含量，以及大鼠血清和肝脏丙二醛（MDA）含量，超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH—Px）活性。结果乌贼墨能显著性降低模型大鼠血清中的TC，TG和LDL-c含量，升高HDL-C，降低动脉粥样硬化指数（LDL-c／HDL-c）；显著提高高脂血症大鼠血清中NO含量；显著降低血清及肝组织中MDA含量，提高SOD和GSH—Px活性。结论乌贼墨可通过调节机体血脂代谢、提高机体内源性抗氧化酶活性，降低机体的过氧化水平，有效预防高脂血症的形成。     

南极磷虾油对高脂血症大鼠血脂和抗氧化力的影响

目的探讨南极磷虾油对实验性高脂血症大鼠血脂和抗氧化力的影响。方法高脂饲料建立高脂血症大鼠模型,分别灌胃50,100和500 mg.kg-1南极磷虾油,连续30 d,测定大鼠血清总胆固醇(TC),甘油三酯(TG),低密度脂蛋白胆固醇(LDL-C),高密度脂蛋白胆固醇(HDL-C)、血清一氧化氮(NO)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)以及丙二醛(MDA)水平。结果南极磷虾油能显著降低高脂血症大鼠血清中的TC、TG和LDL-C含量,降低动脉粥样硬化指数(AI)。提高大鼠血清中NO含量,提高SOD和GSH-PX活性,降低MDA含量。结论南极磷虾油对高脂血症大鼠具有调血脂的作用和抗氧化作用,其抵抗动脉粥状硬化方面的作用优于深海鱼油。     

蒙药童格勒格-1对高脂血症大鼠脂质过氧化的影响

目的观察蒙药童格勒格-1(TGLG-1)对高脂血症大鼠脂质过氧化的影响。方法建立大鼠高血脂模型。高血脂症大鼠分为四组,一组为实验对照组,其余三组分别以低、中、高剂量TGLG-1灌胃,21d后测定血清的NO及肝脏的MDA。结果与高脂对照组相比,中、高剂量TGLG-1能显著增加血清NO含量P<0.05,P<0.01。高剂量组和高脂照组相比肝脏组织MDA含量显著增加P<0.01。结论TGLG-1对血清一氧化氮(NO)肝组织中丙二醛(MDA)有影响。     

蒙药童格勒格-1对高脂血症大鼠脂质过氧化的影响

目的观察蒙药童格勒格-1(TGLG-1)对高脂血症大鼠脂质过氧化的影响。方法建立大鼠高血脂模型。高血脂症大鼠分为四组,一组为实验对照组,其余三组分别以低、中、高剂量TGLG-1灌胃,21d后测定血清的NO及肝脏的MDA。结果与高脂对照组相比,中、高剂量TGLG-1能显著增加血清NO含量P<0.05,P<0.01。高剂量组和高脂照组相比肝脏组织MDA含量显著增加P<0.01。结论TGLG-1对血清一氧化氮(NO)肝组织中丙二醛(MDA)有影响。     

长叶胡颓子降血糖、血脂及抗脂质过氧化作用的研究

目的研究长叶胡颓子果实降血糖、血脂及抗脂质过氧化作用并探讨其药理作用机制.方法以高胆固醇高脂饲料诱发高脂模型大鼠,四氧嘧啶致糖尿病小鼠,应用长叶胡颓子果实水煎液进行实验观察.检测空腹血糖(FBG)、血清胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、胰岛素(INS)、C肽(C-P)及血清脂质过氧化产物丙二醛(MDA)、活性氧(ROS)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)、谷胱甘肽过氧化物酶(GSH-PX)水平.结果长叶胡颓子果实具有抑制高脂血症大鼠TC、TG、LDL-C的升高,降低ROS、MDA,增强SOD、CAT、GSH-PX活力的作用(P＜0.05),可使糖疗病小鼠FBG降低(P＜0.05),对血浆INS和C-P无影响,但胰岛素敏感指数(ISI)明显高于实验对照组(P＜0.05).结论长叶胡颓子果实具有降血糖、血脂和抗脂质过氧化作用,对心血管系统疾病、糖尿病有预防保健作用.     

银杏叶提取物对实验性高脂血症及脂质过氧化作用的影响

目的观察银杏叶提取物（GBE）对高脂血症大鼠血脂代谢及脂质过氧化反应的影响。方法高脂乳剂灌胃30d,同时给大鼠灌胃GBE（40,80,160mg·kg^-1）,测定血清总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL—C）、高密度脂蛋白（HDL-C）的活性,测定血清一氧化氮（NO）、丙二醛（MDA）及超氧化物歧化酶（SOD）活性。结果GBE（80,160mg·kg^-1）组均能明显降低血清TC、TG、LDL—C及MDA的活性（P〈0．05或P〈0．01）,并能显著升高血清HDL—C和NO、SOD的活性（P〈0．05或P〈0．01）。结论GBE能通过调节脂蛋白-胆固醇代谢,改善血管内皮功能、纠正自由基代谢紊乱、促进抗氧化酶活性等途径发挥调脂及抗氧化作用。     

分蘖葱头总黄酮对实验性高脂血症大鼠血脂代谢的影响

目的研究分蘖葱头总黄酮(totle flavone of allium ce-pa L.var agrogatum Don,TFAD)对实验性高脂血症大鼠血脂代谢的影响。方法通过喂饲Wistar大鼠高脂饲料,建立实验性高脂血症模型,并用TFAD进行治疗,测定血清胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白-胆固醇(LDL-C)、高密度脂蛋白-胆固醇(HDL-C)含量,计算动脉硬化指数(AI)。测定血清和肝组织中丙二醛(MDA)和超氧化物歧化酶(SOD)活性,血浆血栓素A2(TXA2)和前列环素(PGI2)的浓度以及血液粘度,并对各组大鼠肝脏进行病理观察。结果TFAD口服25~100μg.g-1,能升高高脂血症大鼠HDL-C,降低TC、TG、LDL-C、AI、TC/HDL-C和MDA的水平,升高SOD活性,增加血浆PGI2,降低TXA2水平,降低全血低切、中切、高切粘度,并能减轻肝细胞脂变程度。结论TFAD能调节实验性高脂血症大鼠血脂代谢,抑制肝脏脂肪沉积,可能与其抗自由基介导的脂质过氧化作用,保持PGI2/TXA2生理平衡,改善血液流变学异常有关。     

Pharmacokinetics of Liquiritigenin in Mice,Rats, Rabbits,and Dogs,and Animal Scale-Up

Pharmacokinetics of liquiritigenin (LQ) and its two glucuronide metabolites, M1 and M2, in mice, rats, rabbits, and dogs and animal scale-up of the pharmacokinetic parameters of LQ were evaluated. After intravenous administration of LQ, the AUC (AUC_0?t) values of LQ, M1, and M2 were proportional to LQ doses in all animals studied. Animal scale-up of some pharmacokinetic parameters of LQ was performed based on the parameters after its intravenous administration (20 mg/kg; in the linear pharmacokinetic range) to the four species. Linear relationships were obtained (r > 0.968) between log CL (or CL/f_u) (L/h) and log species body weight (W) (kg) [CL (or CL/f_u) = 3.29 (34.0) W^{0.723 (0.789)}] and log V_ss (or V_ss/f_u) (L) and log W (kg) [V_ss (or V_ss/f_u) = 0.340 (3.52) W^{0.882 (0.948)}]. Interspecies scale-up of plasma concentration–time data of LQ using apolysichron (complex Dedrick plots) resulted in similar profiles, and plasma concentration–time profile of humans were predicted using the well-fitted four animal data. Our results indicate that the LQ data obtained from laboratory animals could be utilized to generate preliminary estimates of the pharmacokinetic parameters of LQ in humans. These parameters can serve as guidelines for better planning of clinical studies. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:4327–4342, 2009     

Pharmacokinetics, efficacy, and safety of LMWHs in venous thrombosis and stroke in neonates, infants and children

Since the early nineties it has been shown that low molecular weight heparin (LMWH) has significant advantages over unfractionated heparin and oral anticoagulants for both the treatment and the prevention of thrombosis, not only in adults, but also in children. The present review was based on an 'EMBASE', 'Medline' and 'PubMed' search including literature published in any language since 1980 on LMWH in neonates, infants and children. It included paediatric pharmacokinetic studies, the use of LMWH in children with venous thrombosis, LMWH administration in paediatric patients with ischaemic stroke, and its use in order to prevent symptomatic thromboembolism in children at risk. An increasing rate of off-label use of LMWH in children has been reported, showing that LMWHs offer important benefits to children with symptomatic thromboembolic events and poor venous access. Two well-conducted pharmacokinetic studies in this age group showed that neonates and younger infants require higher LMWH doses than older children to achieve the targeted anti-Xa levels, due to an increased extra vascular clearance. Recurrent symptomatic thromboses under LMWH occur in approximately 4% of children treated for venous thrombosis, and in 7% of children treated for stroke; major bleed was documented in 3% of children with therapeutic target LMWH anti-Xa levels, whereas minor bleeding was reported in approximately 23% of children receiving either therapeutic or prophylactic doses, respectively. Further randomized controlled trials are recommended to evaluate the optimum duration and application for different LMWH indications in children.     

Variations in demethylation of N-methylnaltrexone in mice,rats, dogs,and humans

1. Rats and mice have a greater capacity than dogs or humans to N-demethylate the quaternary ammonium compound, N-methylnaltrexone.

2. In dogs, following the i.v. administration of N-[¹⁴C-methyl]methylnaltrexone, 50% of the radioactivity was excreted in the urine and an additional 30% in the faeces within 120h.

3. In humans following the i.v. administration of ¹⁴C-N-methylnaltrexone, 40-60% of the radioactivity was excreted in the urine within the first 24?h. The plasma radioactivity-time curves indicated a biphasic decay and a short distribution phase between 6 and 9?min. with a longer elimination phase between 238 and 1320?min.     

Variations in demethylation of N-methylnaltrexone in mice, rats, dogs, and humans

1. Rats and mice have a greater capacity than dogs or humans to N-demethylate the quaternary ammonium compound, N-methylnaltrexone. 2. In dogs, following the i.v. administration of N-[14C-methyl]methylnaltrexone, 50% of the radioactivity was excreted in the urine and an additional 30% in the faeces within 120 h. 3. In humans following the i.v. administration of 14C-N-methylnaltrexone, 40-60% of the radioactivity was excreted in the urine within the first 24 h. The plasma radioactivity-time curves indicated a biphasic decay and a short distribution phase between 6 and 9 min. with a longer elimination phase between 238 and 1320 min.     

Metabolism of aildenafil in vivo in rats and in vitro in mouse,rat, dog,and human liver microsomes

Aildenafil, 1‐{[3‐(6, 7‐dihydro‐1‐methyl‐7‐oxo‐3‐propyl‐1H‐pyrazolo [4, 3‐d] primidin‐5‐yl)‐4‐ethoxyphenyl] sulfonyl}‐cis‐3, 5‐dimethylpiperazine, a phosphodiesterase type V enzyme inhibitor (PDE5I), is under development for treatment of erectile dysfunction (ED). The purpose of this study was to elucidate metabolism of aildenafil in vivo in rats and in vitro in mouse, rat, dog, and human liver microsomes. Thirty‐one phase I metabolites have been found by LTQ/Orbitrap hybrid mass spectrometry in rat urine, faeces, and bile after oral administration. Major biotransformation pathways of aildenafil included N‐dealkylation of the piperazine ring, hydroxylation and dehydrogenation, aliphatic hydroxylation and loss of alkyl group of piperazine ring. Minor pathways involved hydroxylation on the phenyl ring, pyrazole N‐demethylation, O‐deethylation, loss of piperazine ring (cleavage of N‐S bond) and dehydrogenation on the piperazine ring. Similar metabolic pathways of aildenafil were observed in the incubations of liver microsomes from mouse, rat, and dog as well as from human. The depletion rate of parent drug in mouse and rat liver microsomes was significantly different from that in human liver microsomes. The cytochrome P450 reaction phenotyping analysis was conducted using isozyme‐specific inhibitors. The results indicated that CYP3A was the main isoenzyme involved in oxidative metabolism of aildenafil. Overall, these in vitro and in vivo findings should provide valuable information on possible metabolic behaviours of aildenafil in humans. Copyright © 2013 John Wiley & Sons, Ltd.     

HPLC法同时测定酚氨咖敏颗粒中三组分的含量

目的:建立 HPLC 法同时测定酚氨咖敏颗粒中对乙酰氨基酚、咖啡因、氨基比林的含量。方法:采用日本岛津 VP-ODS色谱柱(150 mm×4.6 mm,5μm),以甲醇-水(40:60)为流动相,流速:1.0 mL·min~(-1),检测波长273 nm,柱温:30℃,进样量:20 μL。结果:对乙酰氨基酚进样浓度在10～100μg·mL~(-1)范围内线性关系良好(r=0.9999),平均回收率(n=3)为98.8%～99.4%;咖啡因进样浓度在2.4～24μg·mL~(-1)范围内线性关系良好(r=0.9999),平均回收率(n=3)为98.2%～101.5%;氨基比林进样浓度在8～80μg·mL~(-1)范围内线性关系良好(r=0.9998),平均回收率(n=3)为98.3%～100.4%。结论:本方法灵敏度高,操作简便、可靠,适用于测定酚氨咖敏颗粒中对乙酰氨基酚、咖啡因、氨基比林的含量。     

Species differences in metabolism and excretion of bromhexine in mice, rats, rabbits, dogs and man

A comparative study of bromhexine metabolism and excretory pathways demonstrated considerable species differences. The rabbit showed almost similarity to the human metabolic pattern, the rat, the least similarity, with the dog and mouse taking up intermediate positions. The formation of 3,5-dibromoanthranilic acid as a further metabolite is reported.     

Metabolism and hepatotoxicity of N,N-dimethylformamide,N-hydroxymethyl-N-methylformamide,and N-methylformamide in the rat

The metabolism and hepatotoxicity ofN,N-dimethylformamide (DMF) and two of its metabolites,N-hydroxymethyl-N-methylformamide (HMMF) andN-methylformamide (NMF) were evaluated over a 4-day period in rats. DMF toxicity was dose dependent and delayed toxicity after the administration of a high DMF dose (13.7 mmol/kg) in comparison to a lower dose (4.1 mmol/kg) was observed. Treatment of rats with 13.7 mmol/kg DMF, HMMF, or NMF showed i) that DMF is more toxic than HMMF or NMR, and ii) that hepatotoxicity occurs later for DMF than for HMMF or NMF. Analysis of serum and urine samples demonstrated that DMF is first metabolized to HMMF, which is then partially converted to NMF. After HMMF administration, NMF was found both in serum and in urine. The time course of DMF and HMMF toxicity in relation to NMF formation fitted the hypothesis that the hepatotoxicity of DMF and HMMF is mediated via NMF. The degree of hepatotoxicity after HMMF and NMF treatment is similar. However, the degree of DMF hepatotoxicity is much higher than in the case of NMF or HMMF. The role of NMF as an obligatory intermediate in DMF and HMMF hepatotoxicity is discussed.