Interactions between carbonic anhydrase and its inhibitors revealed by gel electrophoresis and circular dichroism

Structural properties, and especially the differential stability, of complexes between carbonic anhydrase (CA) and three sulfonamide inhibitors, acetazolamide, dorzolamide and methazolamide, were investigated by spectroscopic and electrophoretic techniques. These included denaturant gradient gel electrophoresis either across a urea or a steady-state transverse sodium dodecyl sulfate (SDS) gradient. Acetazolamide, the smallest and most hydrophilic of the sulfonamides, forms the most stable complex in the presence of urea, whereas dorzolamide, with a bulky and hydrophobic structure, is most stable against the effects of SDS. At pH 7.4, complexes with dorzolamide show minimal changes in mobility across the SDS gradient, as if unaffected by the detergent, both in the presence and in the absence of excess ligand in the gel. When bound to both acetazolamide and methazolamide, on the other hand, CA displays an increase in mobility above 0.05% SDS, lower in the presence than in the absence of excess ligand. The finding of a distinct pattern for the unliganded enzyme, however, suggests the complexes can still retain the ligand, although binding of the surfactant changes their charge density. Under saturating conditions and in the presence of SDS, the surface charge of all complexes is much lower than for unliganded, denatured CA. Circular dichroism (CD) spectra clearly indicate that the increase in secondary structure and the decrease in tertiary structure brought about in CA by the presence of low concentrations of SDS are largely prevented by complexing with the inhibitors. These observations point out peculiar properties of each CA inhibitor, of potential value in the definition of their biological activities and also in the potential development of novel antagonist molecules.     

Radiochemistry teaching and research activities in Brazil

Summary Much concern has been expressed lately about the decline of teaching and research activities in radiochemistry in many countries, as was discussed in an IAEA Technical Meeting in Antalya, Turkey, in 2002, and also at MTAA-11 in Guildford, UK. In the IAEA meeting, a survey was presented about the current situation in different regions of the world (Eastern Europe, East and West Asia, Africa, North America and Latin America) by experts of each region. In the case of Brazil, which has nuclear research reactors and also cyclotrons in operation, the teaching and research activities in radiochemistry are concentrated in the three main institutes of the Brazilian Nuclear Energy Commission, in the University of S?o Paulo and in other universities, in different regions of the country. In the present paper, a closer look is given to the radiochemistry teaching and research activities that are being conducted nowadays in Brazil, comprising: number of radiochemistry courses and students being formed, main research areas being conducted, as well as research and production of radioisotopes for nuclear medicine, using nuclear reactors and cyclotrons.     

黄鸣龙——我国有机化学的一位先驱

黄鸣龙院士(1898-1979)1919年浙江医药专科学校毕业,1924年德国柏林大学有机药物化学博士;1924-1934年任浙江医专教授、主任,卫生署化学部主任;1934-1940年在欧洲先灵公司等从事研究工作;1940年回国在昆明任中研院化学所研究员,兼任西南联大教授;1945年赴美在哈佛大学,默克公司从事研究工作。1952年绕道欧洲回国,先后在中国人民解放军医学科学院化学系和中国科学院上海有机化学研究所任研究员。1955年当选为中国科学院学部委员(院士)。黄先生一生从事有机化学的教育和研究工作,他在有机化学的“结构与机理”以及“反应和合成”二大方面都作出了在国内外具有深远影响的工作。20世纪40年代黄先生发现了变质山道年4个立体异构体的循环转变,堪称立体化学的经典之作;1948年发表了黄鸣龙还原反应;1952年归国后引领和发展了我国的甾体化学研究,带领了我国甾体药物的生产发展,是我国甾体药物工业的奠基人。黄先生治学严谨,既重视应用研究,又强调基础研究;关注学习新知识、新概念,又更重视实验技术。黄先生教书育人,身体力行,是我国有机化学发展的先驱者和奠基人。     

青藏高原湖泊影响锂元素迁移和富集的矿物、元素及环境因素——以西藏郭扎错钻孔沉积物为例

作为我国战略性矿产的锂矿,主要赋存于青藏高原盐湖中。湖泊系统中,锂的富集和迁移规律关系到锂矿的高效提取和未来锂矿的储量估算。本文以西藏咸水湖郭扎错的钻孔沉积物为例,结合AMS14C年代和Mg元素含量变化,系统分析了孔隙水、碳酸盐矿物和硅酸盐矿物的锂含量变化,探讨了矿物、镁元素、环境变化和早期成岩作用等对锂元素迁移和富集的影响。郭扎错沉积物中锂和镁大部分存在于硅酸盐矿物中,锂和镁较高的相关性说明二者存在于相同的硅酸盐矿物中,如粘土矿物。大约90%的锂赋存在硅酸盐矿物中,约8.5%的锂赋存在碳酸盐矿物中,孔隙水中的锂含量占比仅约1.5%。碳酸盐矿物中Mg/Li摩尔比值为78–270,是孔隙水中10多倍,而硅酸盐矿物中的Mg/Li摩尔比值稳定在24–29之间。水–沉积物相互作用促进硅酸盐矿物中锂的释放,咸水环境下释放的锂多于淡水环境下。碳酸盐矿物中,锂和镁主要存在于方解石中。镁离子对锂离子的迁移具有阻碍作用,低温、高盐度下的阻碍作用更强。湖泊沉积物可能是湖水锂的一个重要来源。     

The Therapeutic Potential of Celastrol in Central Nervous System Disorders: Highlights from In Vitro and In Vivo Approaches

Celastrol, the most abundant compound derived from the root of Tripterygium wilfordii, largely used in traditional Chinese medicine, has shown preclinical and clinical efficacy for a broad range of disorders, acting via numerous mechanisms, including the induction of the expression of several neuroprotective factors, the inhibition of cellular apoptosis, and the decrease of reactive oxygen species (ROS). Given the crucial implication of these pathways in the pathogenesis of Central Nervous System disorders, both in vitro and in vivo studies have focused their attention on the possible use of this compound in these diseases. However, although most of the available studies have reported significant neuroprotective effects of celastrol in cellular and animal models of these pathological conditions, some of these data could not be replicated. This review aims to discuss current in vitro and in vivo lines of evidence on the therapeutic potential of celastrol in neurodegenerative diseases, including Alzheimer’s and Parkinson’s diseases, amyotrophic lateral sclerosis, Huntington’s disease, multiple sclerosis, and cadmium-induced neurodegeneration, as well as in psychiatric disorders, such as psychosis and depression. In vitro and in vivo studies focused on celastrol effects in cerebral ischemia, ischemic stroke, traumatic brain injury, and epilepsy are also described.     

Mineral constituents of edible parasol mushroom Macrolepiota procera (Scop. ex Fr.) Sing and soils beneath its fruiting bodies collected from a rural forest area

Concentrations and interrelationships of twenty elements were studied in parasol mushroom and in the top layer of soil (0–10 cm) from the area of Kiwity (Poland). K, P, Mg, Ca, and Zn were found to be the most abundant elements in the mushroom. Higher concentrations of Fe, Mn, Na, Ni occurred in stipes then in caps, while Cd, Cr, Cu, Hg, Rb dominated in caps. Ag, Al, and Ba concentrations in caps and stipes were similar. Parasol mushroom is efficient in up-take and separation of Ag, Cd, Cu, Hg, K (in caps, the bioconcentration factor is BCF ≥ 100), Na, P, Rb (50 < BCF < 100), and Mg, Zn (BCF > 10) in its fruiting bodies, while Al, Ba, Ca, Co, Cr, Fe, Mn, Sr, and Pb are eliminated (BCF < 1). Parasol mushroom from rural forest area in the north-eastern region of Poland is of hygienic concern for human health because of toxic mercury and cadmium content in the edible caps, which are also rich in essential Cu, Fe, and their K, Mn, and Zn content is also high.     

Pesticide residues in groundwaters and soils of agricultural areas in the Águeda River Basin from Spain and Portugal

This research has evaluated the agricultural impact of the use of pesticides in small agricultural areas in the Águeda river basin, which straddles the Spanish-Portuguese border. Sixteen pesticides frequently used in the area, including herbicides, fungicides and insecticides and some of their degradation products, were monitored in 52 groundwater samples and 42 soil samples taken around them, using a developed multi-residual analytical method based on SPE-LC-MS. Sampling was carried out in two different seasons (winter and summer). The results indicated the presence of pesticides at several levels, both in groundwaters and soils. Thirteen of the pesticides studied were detected in one or more of the groundwater samples analysed, but only three pesticides were detected in the soil samples. Terbuthylazine, cyprodinil, tebuconazole and chlorpyrifos were the pesticides most frequently detected in groundwaters, whereas terbuthylazine, metalaxyl and tebuconazole were the sole compounds detected in soils. The distribution of the concentrations in groundwaters indicated that up to 80% and 70% of the samples collected in the summer on the Spanish and Portuguese sides, respectively, exceed the quality standards of 0.1 µg L^?1 for one or more individual compounds and, in turn, up to 64% and 40% exceed the quality standards of 0.5 µg L^?1 for all compounds. The presence of pesticide residues in the groundwaters and soils analysed may well be explained by the use of these compounds in agricultural practices.     

基于MALDI质谱成像技术分析莲子中代谢物的组织分布

该文建立了一种可对莲子中多种代谢物进行高覆盖分析的基质辅助激光解吸附质谱成像(MALDI-MSI)方法,实现了莲子中生物碱类、黄酮类、氨基酸类、脂肪酸类、有机酸类、胆碱类、磷脂类等多种代谢物的组织原位可视化表征。结果表明,生物碱类代谢物主要分布在莲子胚芽中;黄酮类代谢物主要分布在莲子胚芽和种皮中;氨基酸类代谢物在莲子子叶中的含量显著高于莲子胚中;脂肪酸类代谢物在莲子不同组织中的分布差异很小;胆碱类代谢物在莲子胚芽和莲子子叶底部的含量更高,甘油磷酸胆碱在莲子子叶顶部的含量更高;有机酸类代谢物以及绝大多数磷脂类化合物在莲子子叶中的含量高于莲子胚。该研究为评价莲子药物质量、探究莲子中化合物的时-空代谢网络提供了新的技术支持。     

煎煮对几种特色南药中重金属元素含量和形态影响

考察了几种特色南药中重金属(Cd,Cr,Cu,Fe,Mn,Ni,Pb,Sr,Zn)的含量状况,并采用形态连续萃取法分析重金属在药材中的形态分布,研究了药材煎煮时药材中重金属的释放及煎煮过程对药材中重金属形态分布的影响。结果表明,几种南药中Cr,Pb,Zn的含量较高,且巴戟天中的重金属总量高于限量标准;原药材中Cr,Cu,Mn,Ni,Pb和Zn主要存在于有机态和残留态,Fe和Sr主要存在于残留态。煎煮使南药中大量重金属迁移到药汤中;药汤中Cu,Mn,Cr,Pb和Zn主要来自于其在药材中的可交换态、碳酸盐结合态和有机态,而药汤中Sr,Ni和Fe不仅包含其非残留态,更多来自于它们的残留态。为减少药汤中重金属,对于Cu,Mn,Cr,Pb和Zn既要控制在药材中的总量,且需降低它们在药材中的非残留态含量;对于Fe,Ni和Sr则主要是控制其在药材中的总量。     

Micellar medium effects on the hydrolysis of phenyl chloroformate in ionic,zwitterionic, nonionic,and mixed micellar solutions

The spontaneous hydrolysis of phenyl chloroformate was studied in various anionic, nonionic, zwitterionic, and cationic aqueous micellar solutions, as well as in mixed anionic–nonionic micellar solutions. In all cases, an increase in the surfactant concentration results in a decrease in the reaction rate and micellar effects were quantitatively explained in terms of distribution of the substrate between water and micelles and the first‐order rate constants in the aqueous and micellar pseudophases. A comparison of the kinetic data in nonionic micellar solutions to those in anionic and zwiterionic micellar solutions makes clear that charge effects of micelles is not the only factor responsible for the variations in the reaction rate. Depletion of water in the interfacial region and its different characteristics as compared to bulk water, the presence of high ionic concentration in the Stern layer of ionic micelles, and differences in the stabilization of the initial state and the transition state by hydrophobic interactions with surfactant tails can also influence reactivity. The different deceleration of the reaction observed in the various micellar solutions studied was discussed by considering these factors. Synergism in mixed‐micellar solutions is shown through the kinetic data obtained in these media. © 2002 Wiley Periodicals, Inc. Int J Chem Kinet 34: 445–451, 2002     

Physiological changes in barley plants under combined toxicity of aluminum, copper and cadmium

Crop production on acid soil is markedly reduced, further, a multiple heavy metal pollution except Al on acid soil is detected in many areas. The present study was undertaken to assess the toxicities of Al, Cd, and Cu separately and in combinations, three heavy metals very often coexisting on acid soil, and to identify their interactions in two kinds of barley seedlings differing in Al tolerance. The plant growth, metals accumulations, total soluble protein and sugar contents, MDA contents and the activities of SOD and POD were estimated in roots and leaves after 5-week supply of the heavy metals excess in the nutrient solution. The results indicated that the stress treatments including low pH (pH 4.5) alone all adversely affected plant growth and disturbed the cell metabolism seriously. The development of toxic symptoms corresponded to a high accumulation of Al, Cd, Cu and to a poor increase in soluble sugar contents but to a high increase in MDA contents, to the decrease in soluble protein contents and to the much elevated SOD and POD activities in both roots and leaves. In addition, binary metal combinations of Al + Cd and Al + Cu both produced the synergistic response for the growth of barley seedlings, in particular for Shang 70-119, while, ternary metal combination of Al + Cu + Cd produced different interactions in two kinds of genotypes, thus, the significant synergistic response was seen in Shang 70-119, but the antagonistic response was detected in Gebeina. The different responses to ternary metal combination of two genotypes may result from the different metal bioaccumulation patterns, hence, the existence of Cd and Cu promoted Al accumulation in Shang 70-119 but inhibited Al accumulation in Gebeina.     

Investigation of the activity and stability of papain in different micellar systems

Hydrolysis of PyrPheAlaPNa, catalyzed by papain in reverse micelles of ionogenic surfactant of Aerosol OT, and in octane, was studied in the presence and in the absence of nonionogenic surfactants of a different nature. As found, the dependence of the catalytic activity of papain on the hydration degree of the surfactant in reverse micelles of AOT has two maxima, corresponding to the activity of monomeric and oligomeric forms of the enzyme. It was established that the addition of nonionogenic surfactant of a different nature to the Aerosol OT in octane leads to changes of the catalytic properties of the enzyme, in particular, to its activation in the presence of Pluronic L61. Nanoemulsions of nontoxic nonionogenic surfactant and organic solvents, lecithin and Tween 20 in eucalyptus oil were created and characterized; with the use of the photon-correlation spectroscopy technique it was shown that the size of such particles lie in the range from 34 to 266 nm, depending on the water content, nature, and the concentration of system components, and factors regarding its shape lie in the interval 20–30, suggesting the presence of particles with a rod-like shape. It is important to note that in such systems, suitable for use in medicine and cosmetology, the activity of papain was revealed.     

Spectroscopic studies of molybdenum and tungsten enzymes

Molybdenum and tungsten are the only second and third-row transition elements with a known function in living systems. Molybdenum fulfills functional roles in enzyme systems in almost all living creatures, from bacteria through plants to invertebrates and mammals, while tungsten takes the place of molybdenum in some prokaryotes, especially the hyperthermophilic archaea. The enzymes contain the metal bound by an unusual sulfur-containing cofactor. Despite possessing common structural elements, the enzymes are remarkable in the range of different chemical reactions that are catalyzed, although almost all are two-electron oxidation–reduction reactions in which an oxygen atom is transferred to or from the molybdenum. The functional roles filled by molybdenum enzymes are equally diverse; for example, they play essential roles in microbial respiration, in the uptake of nitrogen in green plants, in controlling insect eye color, and in human health. Spectroscopic studies, in particular electron paramagnetic resonance and X-ray absorption spectroscopy, have played an essential role in our understanding of the active site structures and catalytic mechanisms of the molybdenum and tungsten enzymes. This review summarizes the role spectroscopy has played in the state of our knowledge of the molybdenum and tungsten enzymes, with particular regard to structural information on the molybdenum sites.     

石柱黄连及根际土壤中矿质元素特征分析

研究石柱黄连不同器官及其根际土壤中矿质元素特征,探究黄连根茎矿质元素间及其与土壤环境的相关性。采用电感耦合等离子体质谱法(ICP-MS)、电感耦合等离子体发射光谱法(ICP-OES)及原子荧光光谱法(AFS)测定了15组石柱黄连植株和根际土壤中18种矿质元素含量,所得数据运用SPSS 22.0统计软件分析。石柱黄连根际土壤中锰、磷、镁、镉、汞等元素含量的变异性较大,部分采样点土壤中镉含量超过农用地土壤污染风险筛选值。在检测的18种元素中,黄连植株中钙、镁、磷、钾含量最高,其次是铁、锰、锌,再次是锶、铜、镍,最后是铅、钒、钴、镉、钼、铬、砷、汞。须根对大部分矿质元素的富集能力强于根茎或地上部;黄连根茎对锌的富集能力强于须根或地上部;地上部对钙、磷、钾、铬的富集能力强于须根或根茎。Spearman分析表明黄连根茎矿质元素间、黄连根茎与土壤中矿质元素有一定相关性,部分具有统计学意义(P＜0.05)。石柱黄连不同器官中矿质元素含量有明显差异,以此建立的指纹图谱可用于区分黄连根茎及须根的粉末样品;黄连根茎中矿质元素间主要表现为协同作用,黄连根茎与土壤中矿质元素既有协同作用又有拮抗作用。     

Research progress of graphene-based nanomaterials for the environmental remediation

Graphene is a two-dimensional nanomaterial with huge surface area,high carrier mobility and high mechanical strength.Because of its great potential in nanotechnology and environmental protection,it has attracted much attention in environmental and energy fields since its discovery in 2004.Although graphene is a star material,many reviews have introduced its use in terms of energy,the research progress in the field of environment,especially water pollution control,has been rarely reported.Here,we review exhaustively the research progress of graphene-based materials in environmental pollution remediation in the past ten years.Firstly,the advantages and classification of graphene were introduced.Secondly,the research progress and main achievements of graphene and its composites in the fields of photocatalytic degradation,pollutant adsorption and water treatment were emphatically described,and the mechanism of action in the above fields was summarized.Finally,we discuss the problems existing in the preparation and summarize the application of graphene in the environment.     

Analytical strategies to determine antibiotic residues in fish

The accelerated growth of aquaculture has resulted in a series of harmful effects to human health. The widespread and unrestricted use of antibiotics in this industry, to prevent bacterial infections, leads to remaining amounts in the aquatic environment. This has resulted in the emergence of antibiotic-resistant bacteria in aquaculture environments, in the increase in antibiotic resistance in fish pathogens as well as in the transfer of these resistance determinants to human pathogens. Moreover, the use of large amounts of antibiotics may lead to the presence of residual antibiotics in fish tissue and fish products. Fluoroquinolones, tetracyclines, penicillins, sulphonamides and other antibiotics, exhibiting activity against both Gram-positive and Gram-negative bacteria, are widely used for the treatment and prevention of diseases in fish. An extended and comprehensive review on the recent analytical methodologies concerning antibiotic residues in fish reported in the literature is provided in the present article. Emphasis is given on sample preparation regarding isolation and purification, chromatographic conditions and method validation according to legislation. Results of published assays are comparatively presented and criticised.     

Photoactivation of corticosteroids in UVB-exposed skin

The photodegradation of flumethasone (FM) and fluocinolone acetonide (FC) was studied in solution and in the pig skin. Both glucocorticosteroids applied to the pig skin were unstable under UVB light. The photoproducts formed in the skin were the lumi-, photolumi- and andro-derivatives for FM, the same found in vitro. Instead, FC hydroperoxide formed in solution was not found in the skin: the reactivity and oxidative ability of this photoproduct towards biological substrates (lipids, proteins) seems the reason of the lack of its detection in the ex vivo model. In fact, it demonstrated to quickly oxidize amino acids and peptides, and to react with BSA both in the dark and under irradiation. Moreover, the presence in the irradiated pig skin of the FC andro-derivative, which usually forms in H-donating environment, seems consistent with the mechanism of Norrish I fragmentation followed by H-abstraction, likely from the surrounding biological substrates. These findings indicate that photoreactivity of these compounds may take place in the skin of patients exposing themselves to sunlight and is a warning about possible skin damage as a result of that. Furthermore, photolability of these drugs in the skin might cause loss of their therapeutic activity.     

列车员发中微量元素的测定及与消化疾病关系的研究

分析了人体内微量元素的含量及有消化系统疾患者的微量元素变化。最枕后根部头发进行湿法消化,用原子吸收仪测定K、Ca、Fe、Na、Zn、Mg、Mn含量男女间差异有显著性,其中女性K低于男性,其余四种元素含量女性高于男性。男列车员有消化系统疾患者与对照组比较,Zn减少,Mn增加,差异有显著性。可认为列车员职业不影响人体内微量元素水平。     

Site-site memory equation approach in study of density/pressure dependence of translational diffusion coefficient and rotational relaxation time of polar molecular solutions: acetonitrile in water, methanol in water, and methanol in acetonitrile

We present results of the theoretical study and numerical calculation of the dynamics of molecular liquids based on the combination of the memory equation formalism and the reference interaction site model (RISM). Memory equations for the site-site intermediate scattering functions are studied in the mode-coupling approximation for the first-order memory kernels, while equilibrium properties such as site-site static structure factors are deduced from RISM. The results include the temperature-density (pressure) dependence of translational diffusion coefficients D and orientational relaxation times tau for acetonitrile in water, methanol in water, and methanol in acetonitrile--all in the limit of infinite dilution. Calculations are performed over the range of temperatures and densities employing the extended simple point charge model for water and optimized site-site potentials for acetonitrile and methanol. The theory is able to reproduce qualitatively all main features of temperature and density dependences of D and tau observed in real and computer experiments. In particular, anomalous behavior, i.e, the increase in mobility with density, is observed for D and tau of methanol in water, while acetonitrile in water and methanol in acetonitrile do not show deviations from the ordinary behavior. The variety exhibited by the different solute-solvent systems in the density dependence of the mobility is interpreted in terms of the two competing origins of friction, which interplay with each other as density increases: the collisional and dielectric frictions which, respectively, increase and decrease with increasing density.