An investigation of the relationship between BOLD and perfusion signal changes during epileptic generalised spike wave activity

In pathological conditions interpretation of functional magnetic resonance imaging (fMRI) results can be difficult. This is due to a reliance on the assumed coupling between neuronal activity and changes in cerebral blood flow (CBF) and oxygenation. We wanted to investigate the coupling between blood oxygen level dependant contrast (BOLD) and CBF time courses in epilepsy patients with generalised spike wave activity (GSW) to better understand the underlying mechanisms behind the EEG-fMRI signal changes observed, especially in regions of negative BOLD response (NBR). Four patients with frequent GSW were scanned with simultaneous electroencephalographic (EEG)-fMRI with BOLD and arterial spin labeling (ASL) sequences. We examined the relationship between simultaneous CBF and BOLD measurements by looking at the correlation of the two signals in terms of percentage signal change on a voxel-by-voxel basis. This method is not reliant on coincident activation. BOLD and CBF were positively correlated in patients with epilepsy during background EEG activity and GSW. The subject average value of the Delta CBF/Delta BOLD slope lay between +19 and +36 and also showed spatial variation which could indicate areas with altered vascular response. There was not a significant difference between Delta CBF/Delta BOLD during GSW, suggesting that neurovascular coupling to BOLD signal is generally maintained between states and, in particular, within areas of NBR.     

Biaryl scaffold-focused virtual screening for anti-aggregatory and neuroprotective effects in Alzheimer’s disease

Background

Alzheimer’s disease (AD) is a primary cause of dementia in ageing population affecting more than 35 million people around the globe. It is a chronic neurodegenerative disease caused by defected folding and aggregation of amyloid beta (Aβ) protein. Aβ is formed by the cleavage of membrane embedded amyloid precursor protein (APP) by using enzyme ‘transmembrane aspartyl protease, β-secretase’. Inhibition of β-secretase is a viable strategy to prevent neurotoxicity in AD. Another strategy in the treatment of AD is inhibition of acetylcholinesterase. This inhibition reduces the degradation of acetylcholine and temporarily restores the cholinergic function of neurons and improves cognitive function. Monoamine oxidase and higher glutamate levels are also found to be linked with Aβ peptide related oxidative stress. Oxidative stress leads to reduced activity of glutamate synthase resulting in significantly higher level of glutamate in brain. The aim of this study is to perform in silico screening of a virtual library of biaryl scaffold containing compounds potentially used for the treatment of AD. Screening was done against the primary targets of AD therapeutics, acetylcholinesterase, β-secretase (BACE1), Monoamine oxidases (MAO) and N-Methyl-D-aspartate (NMDA) receptor. Compounds were screened for their inhibitory potential by employing molecular docking approach using AutoDock vina. Binding energy scores were embodied in the heatmap to display varies strengths of interactions of the ligands targeting AD.

Results

Several ligands showed notable interaction with at least two targets, but the strong interaction with all the targets is shown by very few ligands. The pharmacokinetics of the interacting ligands was also predicted. The interacting ligands have good drug-likeness and brain availability essential for drugs with intracranial targets.

Conclusion

These results suggest that biaryl scaffold may be pliable to drug development for neuroprotection in AD and that the synthesis of further analogues to optimize these properties should be considered.

     

Magnetic and microstructural properties of M-type strontium hexaferrites with Pr–ZnAl substitution

We have investigated the influence of Pr–ZnAl substitution on the magnetic and microstructural properties of M-type strontium hexaferrites Sr_1.0-xPr_xFe_12.0-x(Zn_0.5Al_0.5)_xO₁₉ (0.0 ≤ x ≤ 0.5) synthesized by the standard ceramic method. X-ray diffraction (XRD) was carried out to determine the crystal structure and the phase identification of the hexaferrites showed that a single magnetoplumbite phase was exhibited in the hexaferrites with Pr–ZnAl content (x) from 0.0 to 0.4 and impurity phase α-Fe₂O₃ was observed in the structure when Pr–ZnAl content (x)?=?0.5. The morphology of the hexaferrites was analyzed by a field emission scanning electron microscopy (FE-SEM). The representative FE-SEM micrographs showed that the particles were regular hexagonal platelets and the average grain size basically kept unchanged with increasing Pr–ZnAl content (x). A magnetic property measurement system was used to measure the magnetic properties of the hexaferrites. The remanence (B_r), maximum energy product [(BH)_max] and H_k/H_cj ratio decreased with increasing Pr–ZnAl content (x) from 0.0 to 0.5. The intrinsic coercivity (H_cj) and magnetic induction coercivity (H_cb) first increased with increasing Pr–ZnAl content (x) from 0.0 to 0.1, and decreased with increasing Pr–ZnAl content (x) from 0.1 to 0.2, and then increased when Pr–ZnAl content (x) ≥ 0.2.     

Crystal structure of triphenylphosphine oxide

The crystal structure of Triphenylphosphine Oxide, C₁₈H₁₅PO, was reinvestigated using Mo-K radiation =0.71069 Å,(Mo-K)=1.36 cm^–1.M _r=278.1, orthohombic,Pbca,a=29.089(3),b=9.1347(9),c=11.261(1) Å,V=2992.2 ų,Z=4,D _x=1.235 Mg m^–3. The structure was refined by full-matrix least-squares toR=0.040 andR _w=0.036 for 1848 unique reflections and 182 variables. Improved bond lengths and angles were obtained; O-P is 1.479(2) Å, weighted means of P-C is 1.803(1) Å, O-P-C is 112.6(1)° and C-P-C is 106.2(1)°.     

Use of Masson's and Jones–Dole equations to study different types of interactions of three pharmacologically important drugs in ethanol

The volumetric and viscometric study of three allopathic drugs (sodium valporate, benzalkonium chloride, and losartan potassium) in ethanol solvent is reported here. This study was carried out at four different temperatures that is, from 288.15 to 318.15 K. The accurately measured density values were used to calculate partial molar volume at infinite dilution, solute–solute interaction parameter, Hepler's constant, partial molar expansivity constant, and isobaric thermal expansion coefficient. The viscosity measurements were carried out for the calculation of constants of Jones–Dole equation and to calculate different thermodynamic parameters of viscous flow which include standard free energy change, standard enthalpy change, and standard entropy change of viscous flow. All these viscometric and volumetric parameters are useful for understanding the different types of interactions of drugs in solution and to study the drug action in body. The results of both volumetric and viscometric studies showed that all drugs had structure promoting effect on solvent, existing of strong solute–solvent interaction, and very weak solute–solute interaction. For all these drugs, solvophobic interaction was found to be dominant over electrostriction. Viscometric studies also showed the existing of stronger solute–solvent interaction in ground state as compared to that in transition state.     

N-Acylbenzotriazole: convenient approach for protecting group-free monoacylation of symmetric diamines

Monatshefte für Chemie - Chemical Monthly - An efficient green route for monoacylation of aromatic diamines, namely o-phenylenediamine and p-phenylenediamine and aliphatic diamines...     

Structural characterization and NMR study of NaNbWO(6) and its proton-exchanged derivatives

The structural characterization of NaNbWO(6), prepared by the ceramic route, has been performed. Electron diffraction has shown the presence of two related phases in a 1:1 ratio, whose lattice parameters correspond to those of the well-known tetragonal tungsten bronzes (TTB) and those of a monoclinically distorted phase. In addition to basic unit cells, the morphology of the two phases has been found to be similar, but they present a slight difference in the W/Nb ratio. (1)H and (23)Na magic-angle spinning nuclear magnetic resonance (MAS-NMR) spectra of NaNbWO(6) and its proton-exchanged derivatives have been interpreted on the basis of the ideal TTB structure. The average structure and the morphology remain unchanged in Na(1-x)H(x)NbWO(6) derivatives. (1)H and (23)Na MAS-NMR spectroscopies have been used to monitor changes produced during exchange processes. It has been shown that the exchange of Na ions is mainly produced, but not exclusively, at tetragonal channels. However, a large amount of Na ions at the pentagonal channels do not exchange with protons, suggesting that these ions are needed to stabilize the TTB-like structure. A tentative distribution of sodium ions in the most-exchanged oxide, deduced from NMR results, approximately (Na(0.46))(p)(Na(0.08))(s)H(0.46)NbWO(6), has been proposed. NMR spectra of Na(1-x)H(x)NbWO(6) indicate that two different OH groups are formed upon exchanging. The study of samples hydrated with D(2)O allowed us to conclude that deuterons of adsorbed water exchange with protons of the two OH groups. The proton-deuteron exchange is slow at room temperature but is strongly enhanced at 90 degrees C. This observation relates to the proton conductivity displayed by exchanged products under a humid atmosphere.     

Investigation of beta-CD-derivatized erythromycin as chiral selector in CE

A novel water-soluble beta-CD-derivatized erythromycin (EM) was synthesized and used as an effective chiral selector for the resolution of chiral compounds in CZE. The purpose of substitution at the primary hydroxyl site of beta-CD with 1-oxygen-2,3-epoxypropane is to produce a compound having functions of both beta-CD and EM. beta-CD-derivatized EM exhibited excellent enantioselectivities compared with single beta-CD and EM for chiral separation in CE. We also investigated the influence of pH and concentration of BGE, concentration of chiral selector, applied potential, and organic modifier on chiral compounds' separation.     

Association between chemical and genetic variation of Vitex rotundifolia populations from different locations in China: its implication for quality control of medicinal plants

Vitex rotundifolia is a widely distributed plant species that has been extensively used in traditional Chinese medicine. Its fruits, Fructus Viticis, are recorded as Manjingzi in the Pharmacopoeia of the People's Republic of China. For the effective quality control of its medicinal values reflected by chemical variation patterns, in addition to the relationship with genetic diversity, analyses based on high-performance liquid chromatographic (HPLC) fingerprinting and inter simple sequence repeat (ISSR) molecular markers were carried out, involving 14 V. rotundifolia populations from different locations in China. The HPLC data showed considerable variation of chemical constituents among the V. rotundifolia populations. The hierarchical clustering analysis further revealed four major groups based on their chemotype variation. Abundant genetic diversity was detected among the V. rotundifolia populations that also were clustered into four groups based on their ISSR data. It is important to point out that the genetic variation pattern revealed by molecular markers was closely associated with that indicated by chemical constitutes in the fruits of V. rotundifolia. This finding provides a solid basis for the combined use of chemical and genetic fingerprints in efficiently evaluating qualities and choosing favourable chemotypes with appropriate pharmacological properties of V. rotundifolia, in addition to establishing good agricultural practices for medicinal plants.     

Stable H and O isotope variations reveal sources of recharge in Dhofar,Sultanate of Oman

Due to the ability of stable water isotopes to characterize the origin of water and connected processes of groundwater recharge, we used the isotope variations of hydrogen and oxygen in different water sources for assessing the recharge process in the Dhofar region. δ¹⁸O and δ²H of precipitation, spring water, and groundwater cover a range from ?10 to +2 and from ?70 to +7?‰ (vs Vienna Standard Mean Ocean Water), respectively, and correlate in a linear relationship close to the Global Meteoric Water Line. No obvious evaporation processes are detected. A clear signal of the recent precipitation is given by the annual monsoon. The monsoon signal is confirmed by several springs existing in the south at the foot of the Dhofar mountains and sources at Gogub above 450?m and Tawi Atir at 650?m above sea level. They occur here first in the form of water intercepted by trees as stemflow and throughflow. The isotope signature of groundwater in the Dhofar mountains reflects the climatic conditions at the time of recharge and the lithological features of the limestone matrix. To the north, the isotope patterns of the groundwater are continuously depleted from the monsoon signal along the outcropping aquifer D (Lower Umm Er Radhuma). Here, a more negative signature towards the wells in the Najd desert region was observed. Cyclone water that flooded wadis in the Dhofar region occasionally, as observed in November 2011, falls isotopically into the same range as we observed in the fossil groundwater. Taking into account the different sources of precipitation and groundwater and thus a clear distinction of the isotopic composition of the water sources, we conclude a recharge process divided into a southward and a northward component in the Dhofar region.