褪黑素对下丘脑氨基酸神经递质的影响

应用纸电泳一双波长薄层扫描法测定了雄性小鼠下丘脑天冬氨酸（Ａｓｐ）．谷氨酸（Ｇｉｎ），及γ－氨基丁酸（ＧＡＢＡ）３种神经递质的含量和褪黑素（ＭＴ）对其影响。结果发现；下丘脑内３种氨基酸神经递质含量均呈明显的昼夜节律性变化，ＭＴ使Ａｓｐ、ＧＡＢＡ的昼夜节律曲线上移，在１２：００及２０：００ｈ升高Ａｓｐ、ＧＡＢＡ作用明显。不同剂量的ＭＴ腹腔注射能够升高Ａｓｐ．ＧＡＢＡ含量，以５μｇ·ｋｇ－１剂量为强，脑室注射ＭＴ的效果更佳。然而，不同浓度，不同时ＩＭＭＴ给药均不影响下丘脑Ｇｌｕ水平。利血平化小鼠的Ａｓｐ、ＧＡＢＡ含量升高，Ｇｌｎ含量则下降、给利血平化动物注射ＭＴ，则ＭＴ对Ａｓｐ，ＧＡ－ＢＡ的影响消失，而使Ｇｌｎ含量进一步下降。提示：ＭＴ对Ａｓｐ、ＧＡＢＡ昼夜节律产生影响，这种影响可能通过单胺神经递质介导。     

热休克蛋白90抑制剂Geldanamycin的抗肿瘤作用研究进展

Ｇｅｌｄａｎａｍｙｃｉｎ(ＧＤＭ )属于苯醌安莎霉素类抗生素 ,其衍生物 17 烯丙胺 17 脱甲氧格尔德霉素 (17 ａｌｌｙｌａｍｉｎｏ 17 ｄｅｓｍｅｔｈｏｘｙｇｅｌｄａｎａｍｙｃｉｎ ,17 ＡＡＧ ) ,目前正进行治疗肿瘤的Ｉ期临床试验 ,这类抗生素还包括ｈｅｒｂｉｍｙｃｉｎＡ和ｍａｃｂｅｃｉｎ。它们的结构特征是一个苯醌部分与一个平面性大环安莎桥相连 (图 1)。现发现苯醌安莎霉素类抗生素的生物活性与分子伴侣 (ｍｏｌｅｃｕｌａｒｃｈａｐｅｒｏｎｅ)热休克蛋白 90 (ｈｅａｔｓｈｏｃｋｐｒｏｔｅｉｎ 90 ,Ｈｓｐ90 )有关。Ｈｓｐ…     

二氢埃托啡耐受后小鼠脑内cAMP含量的减少及氨基酸含量的增加

目的：探讨二氢埃托啡（ＤＨＥ）耐受的机制．方法：放免法及反相高效液相色谱荧光检测法测定环腺苷一磷酸（ｃＡＭＰ）及谷氨酸（Ｇｌｕ）、门冬氨酸（Ａｓｐ）、谷氨酰氨（Ｇｌｎ）、ＧＡＢＡ的含量．结果：ＤＨＥ反复ｓｃ８ｄ后产生耐受．小鼠去小脑全脑Ｇｌｕ、Ａｓｐ、ＧＡＢＡ的基础含量分别由对照组的１４１±２１、３０±０４、１８±０８升高至耐受组的１７２±２２、４１±０６、３２±１０μｍｏｌ／ｇ组织，Ｇｌｎ的含量无明显改变．下丘脑及纹状体的ｃＡＭＰ基础含量分别由对照组的２７１±３８、１８９±３１降至耐受组的９６±１５、６５±２１ｎｍｏｌ／ｇ组织，大脑皮层ｃＡＭＰ的含量无明显改变．结论：ＤＨＥ耐受与脑内Ｇｌｕ、Ａｓｐ、ＧＡＢＡ基础含量的升高及下丘脑、纹状体内ｃＡＭＰ的基础含量的降低有关．     

平阳霉素霜的制备与应用

平阳霉素霜的制备与应用郭随章（江苏省南通市肿瘤医院南通２２６３６１）平阳霉素（Ｐｉｎｇｙａｎｇｍｙｃｉｎ，ＰＹＭ）是临床上常用的抗癌抗生素，属细胞周期非特异性药物（Ｃｅｌｃｙｃｌｅｎｏｎ－ｓｐｅｃｉｆｉｃａｇｅｎｔ，ＣＣＮＳＡ），其作用机理是ＰＹＭ与...     

褪黑素对类风湿关节炎病人外周血淋巴细胞增殖反应的影响及其G蛋白-cAMP信号转导机制的研究

目的研究褪黑素（ＭＴ）对类风湿关节炎（ＲＡ）病人外周血淋巴细胞（ＰＢＬ）增殖反应的影响及其Ｇ蛋白 ｃＡＭＰ信号转导机制。方法淋巴细胞增殖法、ｃＡＭＰ放免测定及Ｇ蛋白功能分析。结果ＲＡ病人ＰＢＬ增殖能力低于正常人１０倍左右，ＭＴ在１×１０－８～１×１０－６ｍｏｌ·Ｌ－１能明显促进ＲＡ病人ＰＢＬ的增殖反应；ＲＡ病人ＰＢＬ的ｃＡＭＰ水平明显高于正常人，ＭＴ（１×１０－６ｍｏｌ·Ｌ－１）可部分使其降低，且ＭＴ的这一作用能被百日咳毒素（ＰＴ）取消。结论ＭＴ可促进ＲＡ病人ＰＢＬ的增殖反应，ＰＴ敏感的Ｇｉ蛋白 ｃＡＭＰ信号转导机制参与了ＭＴ上调ＰＢＬ的作用     

Effects of vitamin C on myocardial mitochondrial function and ATP content in hypoxic rats

ＥｆｅｃｔｓｏｆｖｉｔａｍｉｎＣｏｎｍｙｏｃａｒｄｉａｌｍｉｔｏｃｈｏｎｄｒｉａｌｆｕｎｃｔｉｏｎａｎｄＡＴＰｃｏｎｔｅｎｔｉｎｈｙｐｏｘｉｃｒａｔｓＬＵＯＧａｎｇ１，ＸＩＥＺｅｎｇＺｈｕ２，ＬＩＵＦｕＹｕ，ＺＨＡＮＧＧｕｏＢｉｎ（Ｉｎｓｔｉｔ...     

Apoptosis induced by α─anordrin inhuman promyelocy ticleukemia HL─60cels

Ａｐｏｐｔｏｓｉｓｉｎｄｕｃｅｄｂｙα┐ａｎｏｒｄｒｉｎｉｎｈｕｍａｎｐｒｏｍｙｅｌｏｃｙｔｉｃｌｅｕｋｅｍｉａＨＬ┐６０ｃｅｌｓ１ＬＯＵＬｉ－Ｇｕａｎｇ，ＸＵＢｉｎ（ＳｈａｎｇｈａｉＩｎｓｔｉｔｕｔｅｏｆＭａｔｅｒｉａＭｅｄｉｃａ，ＣｈｉｎｅｓｅＡ...     

争光霉素复合物中两种新组份的研究

从争光霉素产生菌轮枝链霉菌平阳新变种（Ｓｔｒｅｐｔｏｍｙｃｅｓｖｅｒｔｉｃｉｌｌｕｓｖａｒ．Ｐｉｎｇｙａｎ－ｇｅｎｓｉｓｎ．ｓｐ．）的发酵产物争光霉素复合物中分离得到了二种新组份Ｚ－９０１和Ｚ－９０２，通过ＵＶ、ＩＲ、ＣＤ、ＦＡＢＭＳ、１Ｈ－ＮＭＲ、１３Ｃ－ＮＭＲ、１３Ｃ－１ＨＣＯＳＹ等光谱测定，确定了它们的结构，证明它们是二个新的化合物，分别称为ＤｅｐｙｒｕｖａｍｉｄｅＢＬＭＡ５（Ｚ－９０１）和Ｄｅａｍｉｄｅ－Ｄｅｐｙｒｕｖａ－ｍｉｄｅＢＬＭＡ５（Ｚ－９０２）。     

泰唑巴坦合成路线图解

泰唑巴坦合成路线图解张建民，钟超平（上海四药股份有限公司，上海２０００９０）ＧＲＡＰＨＩＣＡＬＳＹＮＴＨＥＴＩＣＲＯＵＴＥＳＯＦＴＡＺＯＢＡＣＴＡＭ￥ＺＨＡＮＧＪｉａｎ－Ｍｉｎ；ＺＨＯＮＧＣｈａｏ－Ｐｉｎｇ（ＳｈａｎｇｈａｉＦｏｕｒｔｈＰｈａｒｍａｃ...     

Inhibitory effects of α-methyl-4-(3-oxo-2H-1,2-benzoisoselenazol-2-yl)benzeneacetic acid on Cu~(2+) and Fe~(2+) induced oxidative modification of human low density lipoprotein

为观察α－甲基－４－（３－氧－２Ｈ－１，２－苯并异硒唑－２－基）苯乙酸（ＭＢＢＡ）对Ｃｕ２＋及Ｆｅ２＋氧化修饰低密度脂蛋白（ＬＤＬ）的保护作用及其作用机理，采用分光光度法测定ＬＤＬ中丙二醛（ＭＤＡ）和共轭双烯（ＣＤ）的产生量．ＭＢＢＡ（０．２－２μｍｏｌ·Ｌ－１）能以剂量依赖性抑制Ｃｕ２＋及Ｆｅ２＋诱导的ＭＤＡ和ＣＤ生成．２μｍｏｌ·Ｌ－１的ＭＢＢＡ对Ｃｕ２＋诱导ＬＤＬ产生ＭＤＡ和ＣＤ的抑制率分别为８９．７％和６０．３％．０．５ｍｍｏｌ·Ｌ－１ＧＳＨ对ＬＤＬ产生ＭＤＡ无影响，但能显著增强ＭＢＢＡ对ＭＤＡ生成的抑制作用．上述结果表明ＭＢＢＡ对ＬＤＬ氧化修饰的抑制作用可能依赖于其ＧＳＨ－Ｐｘ样活性的作用和（或）直接还原脂质氢过氧化物的作用．     

铜离子与平阳霉素络合物的配位构型及活化机理研究

采用1H－NMR技术，应用顺磁离子探针的原理，研究了高自旅顺磁离子Cu2 与平阳霉素在溶液中形成络合物的配位构型状况，得到了其基本构型参数，为研究平阳霉素降解DNA的活化机理提供了结构依据。     

Solution structure of iron(III)-anthracycline complexes.

The interaction of Fe(3+) with the anthracycline anticancer drug idarubicin (Ida) was studied by absorption, CD, M?ssbauer, and EPR spectroscopy. The formation of two major Fe(3+)-Ida complexes, labeled I and II, was observed. In complex I, Fe(3+) ion was bound to anthracycline at the {C(12)=O; C(11)-O(-)} coordination site. In complex II, two Fe(3+) ions were bound at sites {C(5)=O; C(6)-O(-)} and {C(12)=O; C(11)-O(-)}, respectively. Complex I was an equimolar monomeric species with a 1:1 Fe(3+):Ida stoichiometry (beta(1) = 4.8 x 10(11) M(-1)), whereas in complex II the anthracycline ligand was bridging two metal ions, alternatively bound to both anthracycline ring chelating sites with the assumption that the ratio of Fe(3+):Ida in complex II was 2:1 (beta(2) = 5.3 x 10(24) M(-2)). Alternatively, complex II may be oligomeric with Fe(3+):Ida = 1:1 and with each Fe(3+) bridging two Ida molecules. Our findings could be important in understanding the biological effects of the anthracycline-ferric complexes. Thus, providing information about the nature of the Fe(3+)-Ida system, we suggest that the formal 1:3 Fe(3+):anthracycline complexes, reported in the previous literature, could be a mixture of species I, II, and free ligand.     

PROTON MAGNETIC RELAXATION DISPERSION IN HUMAN FLUOROMETHAEMOGLOBIN SOLUTIONS

The solvent proton spin-lattice relaxation time of high spin Fe³⁺(S=5/2) human A fluoromethaemoglobin aqueous solutions was measured at 14 Larmor frequencies in the range from 2.2 to 96 MHz. The observed paramagnetic relaxation rates are analysed in terms of the Solomon-Bloembergen theory, with the g-tensor value of 2 based on the consideration of the protein tertiary structure. From the H₂O (pH 6) haemoprotein solution relaxation data,τ _c = (9.3±0.3) × 10^-10sec. If the total relaxation rates are corrected for the “outer-sphere” paramagnetic contribution, τ_c = (6.5±0.4) × 10^-10sec. The latter correction is obtained from the p.m.r. of the non-exchangeable aliphatic protons of C₂H₄(OD)₂ added to the D₂O-solution of fluoromethaemoglobin. Assuming that single proton transfer is taking place through the protein channel along the axis normal to the haem (g = 2), the proton “binding” site is at a distance of 3.93 to 3.98 Å from the haem Fe³⁺ion.     

Lipophilicity of kinetically labile metal complexes through the example of antidiabetic Zn(II) and VO(IV) compounds

The lipophilic character of several carrier ligands of antidiabetic Zn(II) and VO(IV) metal complexes were characterized by the traditional saturation shake flask method based on n-octanol/water partitioning. The transfer of the neutral ligand species to the organic phase was followed by UV spectrophotometry at various pH and the partition and distribution coefficients were calculated with the help of the proton dissociation constants and the spectra of the individual ligand species. Partition and distribution coefficients of the Zn(II) and VO(IV) complexes were determined by analysis of the metal ion content of the aqueous phases before and after separation by ICP-AES, their UV spectra and the corresponding concentration distribution curves. Results revealed the fairly hydrophilic character both the carrier ligands and their neutral Zn(II) and VO(IV) complexes. A quasi-linear relationship was found between logP of the ligands and that of the metal species in the case of the ligands studied with the exception of the picolinates. Importance of the knowledge of the chemical speciation (i.e. stoichiometry and stability constants) was also highlighted for the characterization of the lipophilic character of the kinetically labile metal complexes.     

Studies of metallobleomycins by electronic spectroscopy, electron spin resonance spectroscopy, and potentiometric titration.

The 1:1 bleomycin-A2-Cu(II) complex shows an absorption maximum at 595 nm (epsilon 120), circular dichroism extrema at 555 nm (delta epsilon + 1.21) and 665 nm (-0.61), and electron spin resonance (ESR) signal with g = 2.211, g = 2.055, and A = 178 x 10(-4) cm-1. The formation constant (log K = 12.630) and deprotonation constant (PKc = 3.585) of the 1:1 bleomycin-Cu(II) complex were determined by computer analysis of potentiometric data. The results of potentiometric titration also indicate that the stability of bleomycin-metal complexes is in the order Fe(II) less than Co(II) less than Ni(II) less than Cu(II) greater than Zn(II) and that these divalent metal complexes have a similar coordination environment. The bleomycin-Cu(II) complex has substantially a square-pyramidal configuration in which the secondary amine nitrogen, pyrimidine(N-1) ring nitrogen, deprotonated peptide nitrogen of histidine residue, and histidine imidazole(N-1) nitrogen coordinate to Cu(II) as planar ligand donors, and the alpha-amino nitrogen as axial donor. The specific Cu(II)-binding site of bleomycin has been compared with that of human serum albumin.     

Flow injection potentiometric determination of bismuth(III) in anti-acid formulations

A flow injection potentiometric procedure is proposed for determining bismuth(III) in anti-acid formulations. In this work, a tubular electrode coated with an ion-pair formed between [Bi(EDTA)](-) and tricaprylylmethylammonium cation (Aliquat 336) in a poly(vinylchloride) (PVC) was constructed and used in a single channel flow injection system. The effect of membrane composition, pH and flow injection parameter over the Bi(III) tubular electrode response (slope (mV/decade)) was initially evaluated in quintuplicate in 0.5 mol l(-1) EDTA solution as carrier. The best response (-59.6+/-0.9 mV/decade) was attained with the 5% m/m ion-pair; 65% m/m o-nitrophenyl octyl ether (o-NPOE) and 30% m/m PVC in pH 6-9. The electrode showed a linear response to E (mV) versus log [Bi(EDTA)](-) in the bismuth(III) concentration range from 2.0x10(-5) to 1.0x10(-2) mol l(-1) and a useful lifetime of at least 5 months (more than 1000 determinations for each polymeric membrane). The detection limit was 1.2x10(-5) mol l(-1) and the R.S.D. was less than 2.0% for a solution containing 5.0x10(-4) mol l(-1) bismuth(III) (n=10). Several species such as Cd(II), Mn(II), Ni(II), Zn(II), Co(II), Cu(II), Mg(II), Cr(III) and Al(III) at 1.0x10(-3) mol l(-1) concentration in 0.5 mol l(-1) EDTA solution did not cause any interference. The frequency rate was 90 determinations per hour and the results obtained for bismuth(III) in anti-acid formulations using this flow procedure and those obtained using a spectrophotometric procedure are in agreement at the 95% confidence level.     

Synthesis,in Vitro and in Vivo Antitumor and Antimicrobial Activities of a Novel Schiff Base Ligand, (e)-ethyl-3-((2-((e)-(2-Hydroxybenzylidene)Amino)Ethyl)Imino)Butanoate and its Transition Metal Complexes

Pharmaceutical Chemistry Journal - Neutral tetradentate N2O2 type complexes of Cr(III), Mn(II), Fe(III), Co(II), Ni(II) and Cu(II) have been synthesized using a mixed Schiff base ligand formed by...     

Redox behaviour of anti-tumor platinum (II) compounds (carboplatin) at solid electrodes

The electroactivity of a cytostatic complex of platinum (II) possessing no halide ligand (carboplatin) has been studied in aqueous media using platinum and carbon paste electrodes. Cyclic voltammetry has been conducted in order to elucidate the redox behaviour of carboplatin as a function of chloride concentration. Reduction was not observed although oxidation was detected. The nature of the compounds formed during the electro-oxidation was directly related to free chloride ions. At the carbon paste electrode, the reduction of the oxidized species occurred in two steps with the formation of cis-platinum structures and a subsequent electrodeposition of platinum particles. The surface modification step at the carbon paste electrode has demonstrated electrocatalytic properties of the electrode towards platinum (II) complexes possessing halide ligands in their structures. Electrodeposition of platinum ions at a platinum electrode surface as well as a judicious choice of working parameters allows quantitative determinations in the concentration range 3 x 10(-4)-1 x 10(-5)M.     

Antiradiation compounds: XXI. Metal ion complexation of bis(methylthio) and methylthio amino derivatives of 1-methylquinolinium-2-dithioacetic acids

With the assumption that the radiation-protective ability (whole body protection of mice) of the bis(methylthio) and methylthio amino derivatives of the 1-methylquinolinium-2-dithioacetic acids may be due to complexation of copper or zinc ions in vivo, the ability of these compounds to form stable metal complexes has been observed. Metal ion stability constants have been determined for three of the compounds with Al(III), Cu(II), Fe(III), and Zn(II) ions, and stabilities somewhat larger than those for simple peptides were found. Structures of the Cu(II) and Fe(III) complexes are proposed, based on elemental analyses and infrared absorption. The Cu(II) complexes are 1:1 ligand:metal structures that precipitated as double salts with CuCl2, and the Fe(III) complexes are 2:1 structures in which the ligands incorporated an additional sulfur atom.     

Complexes between pilocarpine and cobalt(II), nickel(II), copper(II), and zinc(II) ions

The properties of pilocarpine as a ligand toward the halides of cobalt(II), nickel(II), copper(II), and zinc(II) were investigated. Pilocarpine behaved as a monodentate ligand, giving rise to compounds with the general formula methyl(pilocarpine)2X2. The coordinating geometry at the metal ion was pseudotetrahedral in every case. PMR studies showed that the pyridine-type nitrogen of the imidazole ring of pilocarpine was the donor atom of the ligand.