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.     

Pseudo-steady-state solutions for solidification in a wedge

Polubarinova-Kochina's analytical differential equation methodis used to determine the pseudo-steady-state solution to problemsinvolving the freezing (solidification) of wedges of liquidwhich are initially at their fusion temperature. In particular,we consider four distinct problems for wedges which are: freezingwith the same constant boundary temperature, freezing with thesame constant boundary heat fluxes, freezing with distinct constantboundary temperatures and freezing with distinct constant fluxesat the boundaries. For the last two problems, a Heun's differentialequation with an unknown singularity is derived, which in bothcases admits a particularly elegant simple solution for thespecial case when the wedge angle is . The moving boundariesobtained are shown pictorially.     

Design,synthesis, antitubercular and antibacterial activities of pyrrolo[3,2-b]pyridine-3-carboxamide linked 2-methoxypyridine derivatives and in silico docking studies

Abstract

A novel series pyrrolo[3,2-b]pyridine-3-carboxamide linked 2-methoxypyridine derivatives have been designed, synthesized and confirmed by FT-IR, ¹H NMR, ¹³C NMR, ¹⁹F NMR, MS, and elemental analysis. The synthesized compounds were screened for their antitubercular activity using microplate alamar blue assay method and antibacterial activity. Among the tested compounds, 4- fluorophenyl (8m), 4- chlorophenyl (8n) and 4-methoxyphenyl (8i) showed potent anti-TB activity (3.12?µg/mL) in comparison with reference drug, Pyrazinamide ((3.12?µg/mL). In addition, all compounds were docked into DprE1 (PDB code: 4KW5) to explore their binding interactions at the active site. The compounds exhibited essential key interactions as that of reported DprE1 inhibitors and hence, the synthesized compounds may be considered as molecular scaffolds for antitubercular activity. Compounds, 4-chlorophenyl (8n) and 4-flurophenyl (8m) showed significant antibacterial activity against Escherichia coli and Staphylococcus aureus strains. In silico prediction of toxicities, druglikeness and drug score profiles of the tested compounds are promising.     

新型BrФnsted酸性离子液体的合成与表征

制备了五种对水稳定性好、带-SO3H官能团的磺酸类BrФnsted酸离子液体,用核磁共振(NMR)、红外光谱(IR)、电喷雾质谱(ESI-MS)、热重分析(TG)等表征手段对制备的离子液体进行了表征。结果表明,制备的离子液体与预期设计的结构一致,离子液体纯度大于95%;热重分析发现离子液体具有高的热稳定性和较宽的液态范围,其分解温度均高于300℃;五种离子液体均存在四种离子存在形式,H 可以单独以离子形式存在,并不是通常所认为的仅有两种离子存在形式。另外,研究了离子液体在常用溶剂中的溶解性,发现制备的离子液体易溶于水、甲醇,不溶于乙醚、甲苯和乙酸乙酯。     

Quartz resonator signatures under Newtonian liquid loading for initial instrument check

The quartz crystal microbalance (QCM) has been increasingly utilized in the monitoring of the deposition of thin macromolecular films. Studies in the deposition of polymers, biomaterials, and interfacial reactions under electrochemical environment are some of the conditions for the study of these material and deposition properties at a lipid interface. Numerous studies have shown the difficulties in configuring an experimental setup for the QCM such that the recorded data reflect only the behavior of the quartz crystal and its load, and not some artifact. Such artifacts for use in liquids include mounting stress, surface properties such as hydrophobicity, surface roughness coupling to loading liquids, influence of compressional waves, and even problems with the electronic circuitry including the neglect of the quartz capacitance and the hysteretic effects of electronic components. It is thought useful to obtain a simple test by which the user could make a quick initial assessment of the instrument's performance. When a smooth quartz crystal resonator is immersed from air into a Newtonian liquid, the resonance and loss characteristics of the QCM are changed. A minimum of two experimental parameters is needed to characterize these changes. One of the changes is that of the resonant frequency. The second is characterized by either a change in the equivalent circuit resistance (DeltaR) or a change in the resonance dissipation (DeltaD). Two combinations of these observables, in terms of either Deltaf and DeltaR or Deltaf and DeltaD, which we define as Newtonian signatures of S(1) and S(2), are calculated to have fixed values and to be independent of the harmonic and of the physical values of the Newtonian liquid. We have experimentally determined the values of S(1) and S(2) using three different QCM systems. These are the standard oscillator, the network analyzer, and the QCM dissipation instrument. To test the sensitivity of these signatures to surface roughness, which is potential experimental artifact, we determined the values of S(1) and S(2) for roughened crystals and found that these signatures do reflect that experimental condition. Moreover, these results were qualitatively in accord with the roughness scaling factor described by Martin.