The multiple sclerosis functional composite: different practice effects in the three test components

BACKGROUND: The multiple sclerosis functional composite (MSFC) is a multidimensional, MS-specific outcome measure for use in clinical trials, comprising three tests: timed 25-foot walk (T25FW), paced auditory serial addition (PASAT), and 9-hole peg (9HP). OBJECTIVE: To assess interrater and intrarater reliability and practice/fatigue effects in the MSFC. METHODS: The MSFC was administered by two neurologists after a formal training session to 32 MS outpatients. Patients were assessed four times by one examiner and twice by the other. The six tests were administered in a single day, with at least 20 min of rest between them. The examiners were blinded to the results of previous assessments. Testing order was random. RESULTS: Interrater reliability was excellent, with intraclass correlation coefficients (ICC) ranging from 0.93 for 9HP (95% confidence interval [CI] 0.84-0.96) to 0.99 for T25FW (95% CI 0.97-0.99). For intrarater reliability, ICC ranged from 0.93 for PASAT (95% CI 0.82-0.97) to 0.98 for T25FW (95% CI 0.93-1.00). We found no practice effect for T25FW after the first administration. However, performance improved with testing over the first three sessions for PASAT and over the first four sessions for 9HP. CONCLUSIONS: The MSFC is characterised by excellent reliability. Practice effects for the three MSFC components differed, being negligible for T25FW and evident for PASAT and 9HP. To improve efficiency, we suggest one prebaseline administration of T25FW, three of PASAT and four of 9HP.     

Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen, and acetylsalicylic acid

The ecotoxicity of the nonsteroidal anti-inflammatory drugs (NSAIDs) diclofenac, ibuprofen, naproxen, and acetylsalicylic acid (ASA) has been evaluated using acute Daphnia and algal tests. Toxicities were relatively low, with half-maximal effective concentration (EC50) values obtained using Daphnia in the range from 68 to 166 mg L(-1) and from 72 to 626 mg L(-1) in the algal test. Acute effects of these substances seem to be quite improbable. The quantitative structure-activity relationships (QSAR) approach showed that all substances act by nonpolar narcosis; thus, the higher the n-octanol/water partitioning coefficient (log Kow) of the substances, the higher is their toxicity. Mixture toxicity of the compounds could be accurately predicted using the concept of concentration addition. Toxicity of the mixture was considerable, even at concentrations at which the single substances showed no or only very slight effects, with some deviations in the Daphnia test, which could be explained by incompatibility of the very steep dose-response curves and the probit analysis of the data. Because pharmaceuticals in the aquatic environment occur usually as mixtures, an accurate prediction of the mixture toxicity is indispensable for environmental risk assessment.     

电感耦合等离子体——发射光谱法测定冻干人尿标准物质中多种痕量元素

本文研究了用电感耦合等离子体—发射光谱法(ICP-AES)测定冻干人尿标准物质中Be、Cd、Cu、Mn、Ni和Zn的方法.着重探讨了四种尿样的制备方法:消化法、标准加入法、 APDC沉淀法和Chelex-100螯合法.前两种例鲁方法简单方便,适于尿中高浓度元素的测定,后两种制备方法可消除碱金属与碱土金属的干扰.还可富集痕量元素,适于分析尿中含量较低的元素.对NBS SRM 2670冻干人尿标准物质的测定结果表明,各方法具有良好的精密度.     

Deuterated abscisic acid analogs for mass spectrometry and metabolism studies

Four analogs of abscisic acid (ABA) with deuterium atoms at non‐exchangeable positions have been synthesized to be used as standards for quantitation of the plant hormone ABA by mass spectrometry and also to be employed as substrates for metabolism studies. Deuterium atoms were introduced in the side chain of the molecule, at C‐4 and/or C‐5, by deuteride or hydride reduction of a propargylic alcohol, an intermediate in the synthesis. As well, deuterium labels were introduced at the C‐8′ position by conjugate addition of a Grignard reagent containing the label to a cyclohexadienone intermediate, affording specific isotopically labeled ABA molecules with one to five deuterium atoms. Copyright © 2002 John Wiley & Sons, Ltd.     

紫外二阶导数光谱标准加入法测定中药复方制剂中合成鱼腥草素含量

将紫外二阶导数光谱与标准加入法相结合应用于药物分析，定量测定中药复方制剂中合成鱼腥草素的含量。根据比尔定律推导出标准加入体系的含量计算公式为Ｘ＿ｉ＝Ｘ＿ｉ×Ｃ＿ｉ／Ｋ－Ｃ＿ｉ×Ｖ＿ｉ。方法精密度ＣＶ１．３％；平均回收率９９．４０％，回收率ＣＶ１．９％。本法消除了中药复方制剂中样品基质的干扰，结果准确可靠。     

Accessing Chain Length Dependent Termination Rate Coefficients of Methyl Methacrylate (MMA) via the Reversible Addition Fragmentation Chain Transfer (RAFT) Process

Summary: The RAFT‐CLD‐T methodology is demonstrated to be not only applicable to 1‐substituted monomers such as styrene and acrylates, but also to 1,1‐disubstituted monomers such as MMA. The chain length of the terminating macromolecules is controlled by CPDB in MMA bulk free radical polymerization at 80 °C. The evolution of the chain length dependent termination rate coefficient, k, was constructed in a step‐wise fashion, since the MMA/CPDB system displays hybrid behavior (between conventional and living free radical polymerization) resulting in initial high molecular weight polymers formed at low RAFT agent concentrations. The obtained CLD of k_t in MMA polymerizations is compatible with the composite model for chain length dependent termination. For the initial chain‐length regime, up to a degree of polymerization of 100, k_t decreases with α (in the expression k = k · i^−α) being close to 0.65 at 80 °C. At chain lengths exceeding 100, the decrease is less pronounced (affording an α of 0.15 at 80 °C). However, the data are best represented by a continuously decreasing non‐linear functionality implying a chain length dependent α.

     

A Detailed On‐Line FT/NIR and 1H NMR Spectroscopic Investigation into Factors Causing Inhibition in Xanthate‐Mediated Vinyl Acetate Polymerization

Summary: Potential sources of inhibition have been investigated via in situ Fourier transform – near infra‐red (FT‐NIR) and off‐line ¹H NMR spectroscopy in the RAFT/MADIX bulk polymerization of vinyl acetate (VA) in the presence of an O‐isopropyl xanthate, i.e. methyl (isopropoxycarbonothioyl)sulfanyl acetate. The very high reactivity of the vinyl acetate propagating radical makes it vulnerable to oxygen, by‐products generated during the xanthate synthesis, and stabilizers present as impurities. These impurities induce strong and variable inhibition periods in the polymerization. In addition, the MADIX process, using xanthates as reversible chain transfer agents, has been confirmed to be an efficient method for living VA polymerization. Congruent data are obtained when the monomer consumption with time is followed via both ¹H NMR and in situ FT‐NIR spectroscopy. The xanthate‐mediated polymerization of VA exhibits no retardation effects and excellent control of the molecular weight distribution can be achieved, leading to poly(VA) of molecular weights exceeding 50 000 g · mol^?1 with relatively low polydispersities.

     

Xanthate Mediated Living Polymerization of Vinyl Acetate: A Systematic Variation in MADIX/RAFT Agent Structure

Eight xanthates were synthesized to induce living free radical polymerization of vinyl acetate. Four compounds, methyl (4‐methoxyphenoxy)carbonothioylsulfanyl acetate, methyl (methoxycarbonothioyl)sulfanyl acetate, methyl (ethoxycarbonothioyl)sulfanyl acetate and methyl (isopropoxycarbonothioyl)sulfanyl acetate were identified as suitable MADIX/RAFT agents, yielding low polydispersity (PDI < 1.2) poly(vinyl acetate) of molecular weights exceeding 5 × 10⁴ g · mol^?1. All suitable MADIX/RAFT agents exhibited extended periods of inhibition (0.3 h < t_inh < 10 h) and moderate rate retardation. The ability of these compounds to control vinyl acetate polymerization can be correlated with the electron density on the central carbon atom of the xanthate. Electrospray ionization mass spectrometric analysis was performed to complete the investigation on the new MADIX/RAFT agents.

     

Synthesis of two and antibacterial activity of one novel oxime ether derivatives of erythromycin A

The synthesis of novel erythromycin A 9-O-(2-ethenesulfony-ethyl)-oxime and erythromycin A 9-O-(3-oxo-butyl)-oxime from erythromycin A (EA) by the Michael reaction is described and to describe the effects of transformation of ketone in position 9 of EA to an oxime ether. This transformation occurred in a single step without protecting of any functional moiety of erythromycin oxime and zero waste manner in good yield. The antibacterial screen of EA 9-O-(2-ethenesulfony-ethyl)-oxime is also reported.     

Synthesis and preliminary antimicrobial screening of new benzimidazole heterocycles

A series of 2-methylbenzimidazole incorporated to different heterocycles through ethyl or carbamoylethyl groups at position 1 of benzimidazole were synthesized. Also 3-(2-methylbenzimidazol-1-yl)propanoic acid hydrazide incorporated with semicarbazides and thiosemicarbazides were prepared. Moreover, the triazole 5e underwent Michael addition and alkylation reaction. Some of the newly synthesized compounds showed considerable antimicrobial activity against gram positive, negative bacteria and yeast.