运动对小白鼠乳酸脱氢酶(LDH)同工酶的影响初探

经总酶活性测定和凝胶电泳图谱分析发现:剧烈运动后,小白鼠六种组织LDH总酶活性,骨骼肌有显著升高,(p<0.05),其余五种组织均变化不显著;心肌、骨骼肌、肾脏的M型LDH相对活性显著升高(P<0.05),而H型LDH相对活性显著下降(p<0.05);相应地,A亚基比例显著升高,B亚基比例显著下降,这种变化似能反应剧烈运动对小白鼠厌氧代谢的明显影响.     

Studies on the collision‐induced dissociation of adipoR agonists after electrospray ionization and their implementation in sports drug testing

AdipoR agonists are small, orally active molecules capable of mimicking the protein adiponectin, which represents an adipokine with antidiabetic and antiatherogenic effects. Two adiponectin receptors were reported in the literature referred to as adipoR1 and adipoR2. Activation of these receptors stimulates mitochondrial biogenesis and results in an improved oxidative metabolism (via adipoR1) and increased insulin sensitivity (via adipoR2). Hence, adipoR agonists are potentially performance enhancing substances and targets of proactive and preventive anti‐doping measures. In this study, two adipoR agonists termed AdipoRon and 112254 as well as two isotopically labeled internal standards (ISTDs) were synthesized in three‐step reactions. The products were fully characterized by nuclear magnetic resonance spectroscopy (NMR), mass spectrometry (MS) and density functional theory (DFT) computation. Collision‐induced dissociation pathways following electrospray ionization were suggested based on the determined elemental compositions of product ions, comparison to product ions derived from labeled analogs (ISTDs), H/D‐exchange experiments and the results of DFT calculations. The most abundant product ions were found at m/z 174, tentatively assigned to protonated 1‐benzyl‐1,2,3,4‐tetrahydropyridine for AdipoRon, and m/z 207, suggested as protonated 1‐(4‐methoxybenzyl)piperazine, for 112254. Notably, the loss of the heterocyclic ring (i.e. piperazine and piperidine, respectively) in a supposedly intramolecular elimination reaction was observed in both cases. A qualitative determination of both AdipoR agonists in human plasma was established and fully validated for doping control purposes. Validation items such as recovery (86–89%), specificity, linearity, lower limit of detection (1 ng/ml), intraday (3–18%) and interday (5–16%) precision as well as ion suppression or enhancement were determined. Based on these findings adipoR agonists can be implemented in sports drug testing procedures. Copyright © 2015 John Wiley & Sons, Ltd.     

Emerging drugs: mechanism of action,mass spectrometry and doping control analysis

The number of compounds and doping methods in sports is in a state of constant flux. In addition to ‘traditional’ doping agents, such as anabolic androgenic steroids or erythropoietin, new therapeutics and emerging drugs have considerable potential for misuse in elite sport. Such compounds are commonly based on new chemical structures, and the mechanisms underlying their modes of action represent new therapeutic approaches arising from recent advances in medical research; therefore, sports drug testing procedures need to be continuously modified and complementary methods developed, preferably based on mass spectrometry, to enable comprehensive doping controls. This tutorial not only discusses emerging drugs that can be categorized as anabolic agents (selective androgen receptor modulators, SARMs), gene doping [hypoxia‐inducible factor stabilizers, peroxisome‐proliferator‐activated receptor (PPAR)δ‐agonists] and erythropoietin‐mimetics (Hematide) but also compounds with potentially performance‐enhancing properties that are not classified in the current list of the World Anti‐Doping Agency. Compounds such as ryanodine‐calstabin‐complex modulators (benzothiazepines) are included, their mass spectrometric properties discussed, and current approaches in sports drug testing outlined. Copyright © 2009 John Wiley & Sons, Ltd.     

女子三级跳远的生物力学评价

本文建立了一个适合于评价三级跳远技术水平的系统评价框图,并根据这个框图设计了一个决定三级跳远效果的生物力学参数系统利用这个系统分析和评价了当今女子三级跳远亚州记录保持者李惠荣的三级跳远技术(所用技术影片是在1989‘年全国田径冠军赛上用LOCAM型高速摄影机以每秒100帧的速度扫描拍摄的),并通过与男子三级跳远运动员的技术特征的比较,找出了其技术上的优势和不足,并就如何改进和完善其三跳技术提出了一份系统而直观的研究报告,同时为女子三级跳远的再研究提供了可供借鉴的研究方法.     

Modelling match outcomes and decision support for setting a final innings target in test cricket

^** E-mail: p.a.scarf{at}salford.ac.uk This paper considers the problem of timing the declaration ofthe third innings in test cricket. Data on the outcomes of recenttest matches are analysed in order to develop simple decisionsupport tools. The first of these tools presents match outcomeprobabilities given the position of the match at a potentialdeclaration point. These probabilities are determined usinga multinomial logistic regression model that is fitted to thetest match data. This idea is then extended to consider progresstowards a declaration—match outcome probabilities areconsidered as a function of target aimed for and run-rate. Thedecision tools have been implemented on a spreadsheet and examplecalculations are presented. The modelling described has thepotential for practical use in test matches.     

Scheduling fixtures for New Zealand Cricket

^** Email: m.wright{at}lancaster.ac.uk This paper describes the problem faced every year by New ZealandCricket in scheduling the principal inter-regional fixtures.This is a combinatorial optimization problem with few constraintsbut many objectives, which are described in detail. A techniqueknown as Subcost-Guided Simulated Annealing is used to solvethis problem, producing one or more schedules of high quality.One particular feature of the problem requires great care—thedetermination of adequate neighbourhoods for such a tightlyconstrained problem, where most simple changes lead to infeasibility.The approach adopted is to use a complex and unorthodox definitionof a perturbation, each one leading to several possible neighbouringsolutions which are generated by means of a tree search procedure.The system will be used in practice for the 2003–2004cricket season and beyond.     

若干力学参数对跳远成绩的影响

本文建立了考虑空气阻力时,跳远运动员空中位移运动的微分方程.根据量阶比较,求得了该方程的适定解,和已往所发表的不考虑空气阻力时的远度公式比较,定量讨论了风速、空气密度、重力加速度等力学参数对跳远成绩的影响量值.     

Biomonitoring in the mercury-contaminated Wabigoon–English–Winnipeg river (Canada) system: selecting the best available bioindicator

Several organisms used for biomonitoring in the mercury-contaminated Wabigoon–English River System, Ontario, Canada (sport fish, forage fish, crayfish and others) were examined for their utility as bioindicators. Causes for spatial and temporal variability in mercury concentrations in biota are reviewed. The significance of intertrophic and intratrophic biotic relationships is evaluated on both a site-specific and intersite basis. Larger mature fish are the most effective integrators as these organisms are the most buffered from site-specific and seasonal variations in mercury concentrations and bioavailability. Where there are no physical barriers preventing movement of biota between contaminated and uncontaminated parts of the watercourse, younger, smaller organisms can better - ical zones of contamination because of their restricted range. Because many organisms can provide information on mercury contamination, the choice of the most suitable indicator depends upon the purpose of the study, the pharmacokinetics of mercury uptake by the organisms in question, and the chemodynamics of methyl and inorganic mercury species in the field.     

Mass spectrometry of hydantoin-derived selective androgen receptor modulators

N-Aryl-hydroxybicyclohydantoins represent a new class of tissue-selective anabolic agents [selective androgen receptor modulators (SARMs)] and are promising therapeutics as well as drugs prohibited in amateur and professional sport. The dissociation behavior after negative and positive electrospray ionization (ESI) and subsequent collision-induced dissociation (CID) was studied with a drug candidate (BMS 564929) as well as structurally related and isotope-labeled analogs using high resolution/high accuracy orbitrap mass spectrometry. Positive ionization and CID yielded characteristic product ions resulting from the cleavage of the hydantoin structure providing information about the proline-derived nucleus as well as the substituted aryl residue at m/z 96 and 193, respectively. Negative ESI and CID (MS/MS) yielded product ions mainly representing losses of water and CO(2), the latter of which is of particular significance as the hydantoin structure does not contain a carboxyl function. Employing MS(n) experiments with accurate mass determination on six model SARMs, dissociation pathways to characteristic product ions were proposed supporting the identification of these drugs, their metabolites or related compounds in future doping control assays.     

Investigation of the in vitro metabolism of the emerging drug candidate S107 for doping-preventive purposes

The metabolic fate of the emerging drug candidate S107, possessing the potential for misuse as performance-enhancing agent in sports, was investigated by in vitro phase I and II experiments with human microsomal and S9 liver enzymes. The metabolites were identified by liquid chromatography-mass spectrometry with electrospray ionisation in positive mode (LC-ESI-MS/MS). Their collision-induced dissociation behaviour was studied by high-resolution/high accuracy Orbitrap MS(n) analysis, supported by stable isotope labelling, H/D-exchange experiments and density functional theory calculations. Monooxygenation accounted for the main phase I metabolic transformation due to N- and S-oxidation of the 1,4-benzothiazepine core, as substantiated by chemical synthesis, selective reduction methods and characteristic APCI in source fragmentation behaviour of the metabolites. Another dominant metabolic pathway was demethylation, yielding the N- and O-demethylated metabolite, respectively. The latter was further conjugated by glucuronidation as well as sulfonation in subsequent phase II metabolic reactions, whereas the N-demethylated metabolite was not amenable to conjugation. The active drug molecule itself was converted to two glucuronic acid conjugates, which are proposed to consist of two quaternary S107-N(+)-glucuronide isomers. All glucuronides were susceptible to enzymatic hydrolysis with β-glucuronidase (Escherichia coli). A comprehensive LC-ESI-MS(/MS)-based detection method for urine was developed and its fitness for purpose was assessed. The assay can serve as a potential screening and/or confirmation method for S107 in clinical drug testing and doping control analysis in the future.