MRS study of the effects of minocycline on markers of neuronal and microglial integrity in ALS

Objective

Magnetic resonance spectroscopy (MRS) allows to monitor brain metabolites noninvasively in amyotrophic lateral sclerosis (ALS). The objective of this study was to use MRS to monitor the effect of minocycline treatment (200 mg/day) over a short period (6 weeks) on the brain metabolites in the precentral gyrus and brainstem in newly diagnosed ALS patients.

Methods

Ten ALS patients (not on riluzole treatment) were recruited and submitted to single-voxel proton MRS longitudinal examinations (1) before minocycline treatment, (2) 3 weeks and (3) 6 weeks after initiation of treatment.

Results

Results did not show the expected decrease of N-acetylaspartate/creatine (NAA/Cr) in the precentral gyrus, and an increased NAA/Cr ratio in the brainstem suggested neuronal recovery. The myo-inositol (mI)/Cr ratio was unchanged in the precentral gyrus, but increased in the brainstem, indicating a glial reaction.

Conclusions

MRS results suggest that minocycline treatment could be beneficial in the early stages of ALS.     

Influence of the spatial position of a trifluoromethyl group on the 13C chemical shifts in the cyclohexane series

The influence of the introduction of a trifluoromethyl group on the 13C chemical shifts in cyclohexane was examined. The two main effects observed are located at the alpha and gamma positions relative to the carbon bearing the fluorine atoms. By comparison of the collected data it was possible to calculate the increments corresponding to the substitution of a hydrogen atom by a CF3 group at axial or equatorial positions on the cyclohexane ring.     

Future of high pressure liquid chromatography: do we need porosity or do we need pressure?

Making a theoretical study supported by experiments of the kinetic advantages of increased inlet pressures versus increased external porosity using impedance plots of analysis time versus required plate number, it is found that both approaches more or less have the same effect on the kinetic performance. The need to change a given system to one with an increased inlet pressure or with an increased external porosity can best be assessed from the optimal plate number (N(opt)) of the system. When the pursued application requires a plate number that is larger than N(opt), any increase in inlet pressure and external porosity is beneficial. When the required plate number is smaller than N(opt), any increase in inlet pressure and external porosity should preferentially be accompanied by an overall reduction of the feature sizes of the support. The degree to which this feature size reduction can be realized in practice will to a large extent determine which of the two approaches will be the dominant system of the future.     

Molecular rotors: design, synthesis, structural analysis, and silver complex of new [7.7]cyclophanes

New molecular rotors, [7.7](2,6)pyridinocyclophanes (monomers and dimers) embedding 1,3-dioxanes in the bridges, were investigated by variable-temperature NMR, molecular modeling, and single-crystal X-ray diffractometry. The nitrogen-inside rotation of the pyridine ring is more hindered in the derivatives with longer distance between the bridges (i.e., para > meta and 2,6-pyridylene > ortho) and can be chemically stopped by complexation with CF(3)SO(3)Ag. [structure: see text]     

Quantized vortices in the ideal bose gas: a physical realization of random polynomials

We propose a physical system allowing one to experimentally observe the distribution of the complex zeros of a random polynomial. We consider a degenerate, rotating, quasi-ideal atomic Bose gas prepared in the lowest Landau level. Thermal fluctuations provide the randomness of the bosonic field and of the locations of the vortex cores. These vortices can be mapped to zeros of random polynomials, and observed in the density profile of the gas.     

Application of tetraoxadiaza-crown ether derivatives as chiral selector modifiers in capillary electrophoresis

Two new diaza-crown ether derivatives (R-1, RS-1) have been synthesized from 1,4,10,13-tetraoxa-7,16-diazacyclooctadecane and tested as potential chiral selectors in capillary electrophoresis (CE) for the chiral separation of five amino acid derivatives. The individual use of the selectors did not lead to chiral differentiation. However, they enhanced the enantioselective effect of different cyclodextrins in dual selector systems. In this paper, we report the effect of different substituted diaza-crown ether derivatives on the separation results obtained in dual systems with cyclodextrins.     

The Deoxygenation and Isomerization of Artemisinin and Artemether and Their Relevance to Antimalarial Action

The treatment of artemisinin ( 1 ) and β-artemether ( 6 ) with Zn dissolving in AcOH for a few hours results in mono-deoxygenation giving deoxyartemisinin ( 5 ) and deoxy-β-artemether ( 7 ), respectively, as the sole product. In contrast, submission of 1 to FeCl₂ · 4 H₂O in MeCN at room temperature for 15 min causes only isomerization, (3aS,4R,6aS,7R,10S,10aR)-octahydro-4,7-dimethyl-8-oxo-2H-10H-furo[3,2-i] benzopyran-10-yl acetate ( 8 ) and (3R)-3-hydroxydeoxyartemisinin ( 9 ) being produced in 78 and 17% yield, respectively. The action of FeCl₂ · 4 H₂O in MeCN on 6 is similar. Under the same conditions, 6 gives products analogous to 8 and 9 accompanied by an epimeric mixture of 2-[4-methyl-2-oxo-3-(3-oxobutyl)cyclohexyl]propanaldehyde in yields of 32, 23, and 16%, respectively. No epoxide is formed on repeating the last two experiments in the presence of cyclohexene. The deoxygenation of 1 and 6 by Zn is rationalized in terms of its oxophilic nature. The catalyzed isomerization of 1 and 6 by Fe²⁺ is attributed to the redox properties of the Fe²⁺/Fe³⁺ system.     

Covalent attachment of poly(ethyleneglycol) to peptides and proteins

Carbonylimidazol-l-yl-mPEG is obtained quantitatively by reacting methoxypoly(ethyleneglycol) (mPEG) with 1.1 Eq of N,N′-carbonyldiimidazole in the presence of a stoechiometric amount of 4-dimethyl-aminopyridine used as hypernucleophilic acylation catalyst. Carbonylimidazol-l-yl-mPEG is quite stable in aqueous solutions with half-lives up to 70 h in pHs ranging from 6.0 to 7.0 at 25‡C. From reactivity studies toward amines with various nucleophilic strengths, it is suggested that carbonylimidazol-l-yl-mPEG may be best used to modify α-amino terminal function of proteins selectively or to introduce amino function on PEG chains.     

Synthesis,kinetic study,and application of Ti[O(CH2)4OCHCH2]4 in ring‐opening polymerization of ε‐caprolactone and radical polymerization

Ti[O(CH₂)₄OCH?CH₂]₄, used for the ring‐opening polymerization (ROP) of ε‐caprolactone, was synthesized through the ester‐exchange reaction of titanium n‐propoxide and 1,4‐butanediol vinyl ether, and its chemical structure was confirmed by nuclear magnetic resonance (¹H NMR) and thermogravimetric analysis (TGA). The mechanism and kinetics of Ti[O(CH₂)₄OCH?CH₂]₄‐initiated bulk polymerization of ε‐caprolactone were investigated. The results demonstrate that Ti[O (CH₂)₄OCH?CH₂]₄‐initiated polymerization of ε‐caprolactone proceeds through the coordination‐insertion mechanism, and all the four alkoxide arms in Ti[O (CH₂)₄OCH?CH₂]₄ share a similar activity in initiating ROP of ε‐caprolactone. The polymerization process can be well predicted by the obtained kinetic parameters, and the activation energy is 106 KJ/mol. Then, the rheological method was employed to investigate the feasibility of producing the crosslinked poly(ε‐caprolactone)‐poly (n‐butyl acrylate) network by using Ti[O(CH₂)₄OCH?CH₂]₄ as the ROP initiator. The tensile test demonstrates that the in situ generated crosslinked PCL‐PBA network in PMMA matrix provides the possibility of ameliorating the tensile properties of PMMA. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 7773–7784, 2008