Effect of volatile anesthetics on the circular dichroism of bilirubin bound to human serum albumin.

The characteristic circular dichroism of bilirubin bound to human serum albumin undergoes a remarkable sign inversion on addition of halothane, chloroform and other volatile anesthetics. This sign inversion, which is completely reversed by removal of the anesthetic, reflects a pronounced conformational change of the bound ligand; probably a complete inversion of chirality. The observation suggests that association of volatile anesthetics with proteins can markedly alter the internal topography of receptor sites and potentially influence the stereoselectivity of ligand binding.     

A comment on the estimation of times required for the attainment of equilibrium by noncooperative,single site ligand-receptor systems

Summary A table presents the number of hours required for binding to reach 80% and 95% of the equilibrium value for a noncooperative, single site ligand binding system. A 2nd table provides the fraction of binding sites occupied and the fraction of the total ligand bound at equilibrium under the same conditions.     

Identifying the conformational state of bi-liganded haemoglobin

While most researchers agree on the global features of cooperative ligand binding to haemoglobin (Hb), the internal mechanisms remain open to debate. This is not due to inaccurate measurements, but is rather a consequence of the cooperative ligand binding that decreases the equilibrium populations of the partially liganded states and makes observation of the transitions between these substates more difficult. For example, the equilibrium population of the doubly liganded tetramers is typically less than 5% of the total Hb. As a result many models with widely varying mechanisms may fit the oxygen equilibrium curve, but may not be consistent with observations of other parameters, such as ligand-binding kinetics or subunit association equilibria. The wide range of methods and models has led to divergent conclusions about the properties of specific substates. One notable debate concerns the properties of the doubly liganded forms. The simple two-state model predicts a shift in the allosteric equilibrium based on the number of ligands bound, but not on their distribution within the tetramer. From studies of dimer-tetramer equilibria of various pure and hybrid forms, it was concluded that a tetramer with two ligands bound on the same α β dimer (species 21, an asymmetric hybrid) shows an enhanced tetramer stability, similar to singly liganded Hb, relative to the other three types of doubly liganded tetramers which resemble the triply liganded forms [Ackers et al. (1992), Science 255: 54–63]. The implications of this model and the relevant experiments will be reviewed here. Received 27 April 1998; received after revision 17 July 1998; accepted 10 August 1998     

Strategies for the design of inhibitors of aldose reductase, an enzyme showing pronounced induced-fit adaptations

Aldose reductase is involved in the polyol pathway, catalyzing the reduction of glucose to sorbitol. However, due to pronounced binding site adaptations, the enzyme can operate on a broad palette of structurally diverse substrates ranging from small aliphatic and aromatic aldehydes up to steroid-type ligands. A comparative analysis of the presently accessible crystal structures of aldose reductase complexes reveals four binding-competent protein conformations. Additional relevant conformers are detected through molecular dynamics simulations. They indicate an equilibrium of several conformers which is shifted towards the binding-competent geometries upon ligand binding. Such a manifold system with several alternative binding site conformers requires some tailored concepts in virtual screening. We followed two strategies, both successfully suggesting new micromolar inhibitors. In a first attempt, we concentrated on one preferred conformer and performed a virtual screening, assuming that the binding pocket of aldose reductase adopts only this conformation. In a second approach, we followed a ligand superpositioning method. Ligands were extracted in their bound conformations from three different crystal structures, all accommodating the ligands with different active site conformations. After merging these ligands into one supermolecule, mutual alignments were computed, taking candidate ligands from a screening database. The latter strategy also retrieved several structurally new inhibitors of micromolar potency.     

Investigating metal-binding in proteins by nuclear magnetic resonance

Metal ions play a key role for the function of many proteins. The interaction of the metal ion with the protein and its involvement in the function of the protein vary widely. In some proteins, the metal ion is bound tightly to the ligand residues and may be the key player in the function of the protein, as in the case of blue copper proteins. In other proteins, the metal ion is bound only temporarily and loosely to the protein, as in the case of some metalloenzymes and other proteins where the metal ion acts as a cofactor necessary for the function of the protein. Such proteins are often known as metal ion-activated proteins. The review focuses on recent nuclear magnetic resonance (NMR) studies of a series of metal-dependent proteins and the characterization of the metal-binding sites. In particular, we focus on NMR techniques for studying metal binding to proteins such as chemical shift mapping, paramagnetic NMR and changes in backbone dynamics upon metal binding. Received 12 October 2006; received after revision 30 November 2006; accepted 5 February 2007     

Conformation and local anesthetic activity of carbanilates

Summary The influence of spatial configuration on intensity, onset, and duration of anesthetic effect has been observed in some carbanilate local anesthetics of fixed conformation. Synthesis of the carbanilates is described.     

The pH-dependence of glucose transport inhibition by local anesthetics in human erythrocytes

Summary Local anesthetics vary in inhibition of glucose transport in human erythrocytes at different pH-values in the incubation media.The authors thank Dr G. Zimmer for valuable discussions. The work was supported by the Deutsche Forschungsgemeinschaft.     

Décharge catalytique du proton en présence de séléno-cystine et de nickel

Summary It has been found that seleno-cystine, reduced to seleno-cysteine and bound in ligand form to nickel ion, produces catalytic hydrogen discharge in slight acid media. This discharge occurs in the region of a catalytic prewave located at more positive potentials (E_1/2=–1.14 V, S.C.E.) compared with the normal wave of H₃O+(E_1/2=–1,67 V, S.C.E.).     

RNA-synthesis in rat kidneys after fluorinated anesthetics or inorganic fluoride administration.

RNA-synthesis in rat kidneys is affected by the administration of 0.5% methoxyflurane and 1% enflurane; also fluoride, a product of fluorinated anesthetics metabolism, hinders renal RNA-synthesis in rats.     

Eine neue Reihe lokalanästhetisch wirksamer basischer Acetylmesidine

Summary Highly active, and relatively little toxic, local anesthetics were developed from the group of substituted acetylmesidines. The substances were tested for toxicity and local anesthetic activity in surface and infiltration anesthesia.     

Eine neue Gruppe hochwirksamer Lokalanästhetika

Summary Highly active and relatively little toxic local anesthetics from the group of diethylaminoethylesters of alkoxydiphenylcarbamic acids were developed. The substances were tested for local anesthetic activity in surface and infiltration anesthesia.     

Chromosomal localization of the locus PGM (phosphoglucomutase) inDrosophila buzzatii

Summary The locus PGM ofD. buzzatii is localized in the linkage group of chromosome 4, outside the region blocked by the inversion 4s and with a recombination percentage of about 16% from the inversion breakpoint.     

RNA-synthesis in rat kidneys after fluorinated anesthetics or inorganic fluoride administration

Summary RNA-synthesis in rat kidneys is affected by the administration of 0.5% methoxyflurane and 1% enflurane; also fluoride, a product of fluorinated anesthetics metabolism, hinders renal RNA-synthesis in rats.Acknowledgments. This work was supported by a grant from C.N.R., Roma.     

金银藤挥发油成分的气-质联用分析与化学计量学解析

目的 定性、定量分析金银藤挥发油成分.方法 采用气相色谱-质谱进行检测,通过化学计量学解析法对二雏色谱/质谱数据进行解析,得到各组分的纯色谱曲线和质谱,从而实现对金银藤挥发油成分的定性、定量分析,并结合程序升温保留指数来鉴定化合物.结果 金银藤的挥发油鉴定了39个成分,定性组分含量占金银藤挥发油成分总含量的94.54%.结论 全银藤挥发油的主要成分为十六烷酸（45.86%）、9,12-十八碳二烯政乙酯（39.02%）、十四烷酸（1.8%）、十五烷酸（1.07%）、十八烷酸（1.02%）.     

Lipid sensing and lipid sensors

Translation of nutrient stimuli through intracellular signaling is important for adaptation and regulation of metabolic processes, while deregulation by either genetic or environmental factors predisposes towards the development of metabolic disorders. Besides providing energy, fatty acids act as prominent signaling molecules by altering cell membrane structures, affecting the lipid modification status of proteins, and by modulating ligand-activated nuclear receptor activity. Given their highly hydrophobic nature, fatty acids in the aqueous intracellular compartment are bound to small intracellular lipid binding proteins which function as intracellular carriers of these hydrophobic components. This review describes recent advances in identifying intracellular pathways for cytosolic fatty acid signaling through ligand activated receptors by means of small intracellular lipid binding proteins. The mechanism behind intracellular fatty acid transport and subsequent nuclear receptor activation is an emerging concept, and advances in understanding this process provide new potential therapeutic targets towards the treatment of metabolic disorders.     

Endocrine and environmental aspects of sex differentiation in fish

This paper reviews the current knowledge concerning the endocrine and environmental regulations of both gonadal sex differentiation in gonochoristic and sex inversion in hermaphroditic fish. Within the central nervous system, gonadotropins seem to play a role in triggering sex inversion in hermaphroditic fish. In gonochorists, although potentially active around this period, the hypothalamo-pituitary axis is probably not involved in triggering sex differentiation. Although steroids and steroidogenic enzymes are probably not the initial triggers of sex differentiation, new data, including molecular approaches, have confirmed that they are key physiological steps in the regulation of this process. Environmental factors can strongly influence sex differentiation and sex inversion in gonochoristic and hermaphroditic fish, respectively. The most important environmental determinant of sex would appear to be temperature in the former species, and social factors in the latter. Interactions between environmental factors and genotype have been suggested for both gonochoristic and hermaphroditic fish.     

常用全身麻醉药对炎性细胞因子的影响

在手术、创伤、应激等因素所致的炎症中,细胞因子起着重要作用。炎性细胞因子产生和释放过多,破坏了致炎因子和抗炎因子的平衡,从而引起炎症反应。适当的炎症反应可以起到抵抗损伤和修复创伤等防御作用;过度的炎症可致手术后感染、组织修复不良甚至诱发机体感染性休克和多器官功能障碍综合征（MODS）。常用全麻药对细胞因子具有一定的影响和潜在的调节作用,越来越受到麻醉医生的重视。本文就近几年的研究现状作一综述。     

The effects of continuous chloroform and halothane anesthesia on plasma prolactin levels in ovariectomized estrogen-treated rats

Summary In ovariectomized, estrogen-treated rats bearing indwelling aortic catheters, continuous inhalation of chloroform or halothane resulted in increases in plasma prolactin levels 10 min after the exposure to the anesthetics. The plasma prolactin levels over the subsequent 2 h, however, were not significantly different from that of the control animals.Supported by NSF Research Grant BMS 74-17332.The authors wish to express their appreciation to Mrs Cynthia Van De Walle for her outstanding assistance in the performance of the prolactin RIA and the art work.     

Nuovo tampone volatile da impiegarsi in cromatografia ed elettroforesi

Summary A volatile ethilendiamine-acetate buffer is described which is capable of keeping the pH unaltered during volatilization. The advantages of this buffer in electrophoretic and chromatographic procedures, in comparison with other volatile buffers, are discussed.