家兔静注水杨醛-N'-(2-呋喃硫羰基)腙铜配合物的药物动力学

目的：研究水杨醛－Ｎ′－（２－呋喃硫羰基）腙铜配合物（ＣＳＦＣ）在兔体内的药物动力学。方法：１０只家兔静脉注射ＣＳＦＣ５ｍｇ·ｋｇ－１，用反相ＨＰＬＣ法测定血清药物浓度。结果：ＣＳＦＣ的血药浓度－时间曲线符合二室开放模型，主要药动学参数为：Ｔ１２α＝３．４±１．７ｍｉｎ，Ｔ１２β＝６５．５±１４．６ｍｉｎ，Ｋ１２＝０．１１８３±０．０６６９ｍｉｎ－１，Ｋ２１＝０．０２２８±０．００６５ｍｉｎ－１，Ｋ１０＝０．１２０２±０．０４０７ｍｉｎ－１，Ｖ０＝０．３０５±０．１８４Ｌ·ｋｇ－１，ＣＬ＝１．８９６±０．４７０Ｌ·ｋｇ－１·ｈ－１，ＡＵＣ＝１７０．１±５７．０ｍｇ·ｍｉｎ－１·Ｌ－１。结论：ＣＳＦＣ在兔体内分布迅速而广泛，消除也较快。家兔静注５ｍｇ·ｋｇ－１，可维持抗结核杆菌有效血浓度６ｈ。     

聚醋酸乙烯酯与铜（Ⅱ）离子的配位反应及其催化作用

以ＥＳＲ、ＵＶ和ＩＲ表征Ｃｕ（２＋）离子与ＰＶＡＣ的配位反应。根据ＣＵＣｌ２·２Ｈ２Ｏ乙醇溶液与ＰＶＡｃ－ＣｕＣｌ２·２Ｈ２Ｏ乙醇溶液的电导率差值随Ｃｕ（２＋）离子摩尔浓度变化的明显转析点得知，１个Ｃｕ（２＋）离子大约能与ＰＶＡｃ４个链节单元配位。证实ＭＭＡ在Ｃｕ（Ⅱ）－ＰＶＡｃ配合物／Ｎａ２ＳＯ３体系的聚合体是无规ＰＭＭＡ，得率为７０％。讨论了ＭＭＡ在Ｃｕ（Ⅱ）－ＰＶＡｃ配合物／Ｎａ２ＳＯ３体系络合催化引发下的游离基反应历程。     

宫内节育器(Cu-IUD)体外释放Cu~(2+)以及含药Cu-IUD体外释放吲哚美辛的研究

目的:比较含Cu及含消炎药IUD释放Cu2+和吲哚美辛(IMC)的释放行为。方法:通过模拟人体宫腔内环境,采用火焰原子吸收光谱仪和UV-752分光光度仪测定TCu380A IUD、MLCu375 IUD和元宫型药Cu365IUD 300d内Cu2+和320d内IMC的释放行为。结果:3种Cu-IUDs的Cu2+都呈现了双相的释放行为:初始阶段的快速释放与随后的稳定缓慢释放。元宫型药Cu365IUD的Cu2+释放为零级过程,其内IMC的体外释放结果符合Weibull方程。结论:3种型号中,元宫型药Cu365IUD中Cu2+的释放最为稳定。依据IMC的体外释放特点,可以解释含药Cu-IUD防治置IUD副作用的功能。     

Chemical Pathways of Peptide Degradation. X: Effect of Metal-Catalyzed Oxidation on the Solution Structure of a Histidine-Containing Peptide Fragment of Human Relaxin

Purpose. To elucidate the major degradation products of the metal-catalyzedoxidation of (cyclo S-S) AcCys-Ala-X-Val-Gly-CysNH₂(X = His, cyclic-His peptide), which is a fragment of the proteinrelaxin, and the effect of this oxidation on its solution structure. Methods. The cyclic-His peptide and its potential oxidative degradationproducts, cyclic-Asp peptide (X = Asp) and cyclic-Asn peptide(X = Asn), were prepared by using solid phase peptide synthesisand purified by preparative HPLC. The degradation of the cyclic-Hispeptide was investigated at pH 5.3 and 7.4 in an ascorbate/cupricchloride/oxygen [ascorbate/Cu(II)/O₂] system in the absence or presenceof catalase (CAT), superoxide dismutase (SOD), isopropanol, andthiourea. The oxidation of the cyclic-His peptide was also studied in thepresence of hydrogen peroxide (H₂O₂). All reactions were monitored byreversed-phase HPLC. The main degradation product of the cyclic-Hispeptide formed at pH 7.4 in the presence of ascorbate/Cu(II)/O₂was isolated by preparative HPLC and identified by ¹H NMR andelectrospray mass spectrometry. The complexation of Cu(II) with thecyclic-His peptide was determined with ¹H NMR. The solution structureof the cyclic-His peptide in the presence and absence of Cu(II) at pH5.3 and 7.4 and the solution structure of the main degradation productwere determined using circular dichroism (CD). Results. CAT and thiourea were effective in stabilizing the cyclic-Hispeptide to oxidation by ascorbate/Cu(II)/O₂, while SOD and isopropanolwere ineffective. Cyclic-Asp and cyclic-Asn peptides were notobserved as degradation products of the cyclic-His peptide oxidized atpH 5.3 and 7.4 in an ascorbate/Cu(II)/O₂ system. The main degradationproduct formed at pH 7.4 was the cyclic 2-oxo-His peptide (X = 2-oxo-His).At pH 5.3, numerous degradation products were formed inlow yields, including the cyclic 2-oxo-His peptide. The cyclic 2-oxo-Hispeptide appeared to have a different secondary structure than didthe cyclic-His peptide as determined by CD. ¹H NMR results indicatecomplexation between the cyclic-His peptide and Cu(II). CD resultsindicated that the solution structure of the cyclic-His peptide in thepresence of Cu(II) at pH 5.3 was different than the solution structureobserved at pH 7.4. Conclusions. H₂O₂ and superoxide anion radical ( ) were deducedto be the intermediates involved in the ascorbate/Cu(II)/O₂-inducedoxidation of cyclic-His peptide. H₂O₂ degradation by a Fenton-typereaction appears to form secondary reactive-oxygen species (i.e.,hydroxyl radical generated within complex forms or metal-bound formsof hydroxyl radical) that react with the peptide before they diffuse intothe bulk solution. CD results indicate that different complexes areformed between the cyclic-His peptide and Cu(II) at pH 5.3 and pH7.4. These different complexes may favor the formation of differentdegradation products. The apparent structural differences between thecyclic-His peptide and the cyclic 2-oxo-His peptide indicate that conformationof the cyclic-His peptide was impacted by metal-catalyzedoxidation.     

Long-lasting contractile action and the inhibitory action of cupric ions on ileal longitudinal muscle

Cupric ions (Cu(2+)), at concentrations above 0.03 mM, induced a progressive increase in the tonic contraction of guinea-pig ileal longitudinal muscle. Maximal contraction of 0.1 mM Cu(2+) attained a level above that of the 60-mM K(+)-induced tonic response, within 20 min of application. The tension induced by Cu(2+) persisted for more than several hours. Tetrodotoxin (3 x 10(-6) M) had no effect on the contraction induced by 0.1 mM Cu(2+). After incubation in a Ca(2+)-free medium, the ileal response to 0.1 mM Cu(2+) was lost. Nifedipine, a L-type Ca(2+) channel blocker, dose-dependently inhibited contractions induced by Cu(2+). As the duration of the first application of 0.1 mM Cu(2+) increased above 30 min, after washing with normal medium, the contractile response to a second application of 0.1 mM Cu(2+) decreased gradually. After 150 min of the first application of 0.1 mM Cu(2+), a second application of Cu(2+) could not evoke any contraction. After the application of 0.1 mM Cu(2+) for 150 min, when muscles were washed with a medium containing 1 mM EDTA, the response to 0.1 mM Cu(2+) returned to a greater extent in the normal Ca(2+) medium. In conclusion, Cu(2+) (0.1 mM) induced a maximal ileal tension above that of the K-induced tonic response within 20 min. The ileal contraction to Cu(2+) persisted for more than several hours and depended on extracellular Ca(2+) concentrations. It is possible that a part of Cu(2+), bound to a EDTA-inaccessible site, also has a tension inhibitory effect.     

不同含铜宫内节育器在模拟宫腔液中的铜离子释放研究

目的 测定不同含铜宫内节育器在模拟宫腔液中的铜离子释放,进而拟合出铜离子的释放方程.方法 采用火焰原子吸收法测定铜,并对测定方法进行了方法学考察.利用Excel趋势回归分析预测铜离子的释放.结果 TCu220C-IUD的时间与铜离子释放呈指数函数回归关系,其他宫内节育器的时间与铜离子释放呈幂函数回归关系.铜离子释放量的变化受观测值的变化影响所占比例为94.21％～98.07％.结论 运用火焰原子吸收法及Excel回归分析可得出各种含铜宫内节育器的铜离子的释放.TCu380A-IUD的铜离子的暴释现象最严重.     

利福平含量的螯合分光光度测定

基于利福平与铜离子螯合形成稳定的深紫色螯合物，在５６２ｎｍ处有最大吸收，可进行分光光度测定。方法简便、快速、准确。回收率为９９．４０％，变异系数为０．１９％。     

模拟宫腔液成分对铜/低密度聚乙烯纳米复合材料宫内节育器中铜离子(Cu~(2+))释放的影响

目的:研究模拟宫腔液成分对铜/低密度聚乙烯(Cu/LDPE)纳米复合材料宫内节育器(IUD)中Cu2+释放的影响。方法:根据模拟宫腔液的成分和浓度配制了6种浸泡溶液,用紫外分光光度计测试复合材料IUD在浸泡溶液中Cu2+的释放速率,用标准接触角仪测试复合材料与浸泡溶液的接触角,用pH计测试浸泡溶液的pH值。结果:模拟宫腔液成分可改变溶液与复合材料的接触角,以及浸泡溶液的pH值,进而对复合材料IUD的Cu2+释放速率产生较大影响。含Cl-无机正盐、葡萄糖、人血白蛋白能加速Cu2+的释放,但酸式盐的加入使Cu2+释放速率降低。结论:模拟宫腔液成分对复合材料IUD的Cu2+释放速率产生较大影响。     

Specific cleavage of immunoglobulin G by copper ions

The hinge region of a recombinant-DNA-produced human IgG₁ (Campath 1H) is specifically cleavable at a single copper-sensitive peptide bond, yielding a distinct fragment resolved by size-exclusion high-performance liquid chromatography. This novel metal ion-catalysed cleavage at slightly alkaline pH is inhibited by EDTA and its rate is reduced at slightly acidic conditions (pH5-6) and accelerated by increasing concentrations of cupric ion and higher temperature. Complete cleavage was observed after incubation at pH 8 for 24 h with 1 mM CuC1₂. Sequence analysis determined the cleavage site to be the Lys₂₂₆-Thr₂₂₇ bond in the hinge-region sequence DKTHT. Cleavage of other IgGs was observed to varying degrees, and specific cleavage of synthetic peptides containing this pentapeptide sequence was also observed. © Munksgaard 1996.     

CuS表面改性聚丙烯腈纤维的结构及导电机理的研究

研究了用一步反应法制备的CuS表面改性的聚丙烯腈导电纤维的微观结构、导电性和温度的变化规律及其导电机理,观察了CuS在纤维表面上的结晶态及晶型变化现象,证实了该导电纤维的以电子导电为主的导电机理。