Synthesis,acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activities,and molecular docking studies of a novel compound based on combination of flurbiprofen and isoniazide

Synthesis of a compound with balanced bioactivities against a specific target is always a challenging task. In this study, a novel compound (1) has been synthesized by combination of flurbiprofen and isoniazide and shows ∼2.5 times enhanced acetylcholinesterase (AChE) inhibition activity and ∼1.7 times improved butyrylcholinesterase (BuChE) inhibition activity compared to flurbiprofen and a standard drug (i.e. physostigmine). A comparative AutoDock study has been performed, based on the optimized structure, by the DFT/B3LYP method, which confirmed that compound (1) is more active against AChE and BuChE, with calculated binding energies of −12.9 kcal mol⁻¹ and −9.8 kcal mol⁻¹ respectively as compared to flurbiprofen and an eserine (physostigmine) standard for which the binding energy was calculated to be −10.1 kcal mol⁻¹ and −8.9 kcal mol⁻¹, respectively. A mixed mode of inhibition of AChE and BuChE with compound 1 was confirmed by Lineweaver–Burk plots. AChE and BuChE inhibition activity alongside docking results suggests that compound (1) could be used for treatment of Alzheimer''s disease. Moreover, compound (1) also exhibit better α-chymotrypsin activity compared to flurbiprofen. Furthermore, in vitro and in vivo analysis confirmed that compound (1) exhibit more activity and less toxicity than the parent compounds.

A novel compound (1) shows ∼2.5 and ∼1.7 times enhanced AChE inhibition activity and BuChE inhibition activity respectively compared to flurbiprofen and standard drug (i.e. physostigmine). It has also been confirmed by comparative AutoDock studies.     

Diastolic asynchrony and myocardial dysfunction in patients with univentricular heart after Fontan operation

Background

We aimed to assess the existence of myocardial dysfunction and intra-univentricular diastolic asynchrony in patients after Fontan operation.

Methods

Twenty patients after Fontan procedure and 30 age-matched controls were included in the study. The global function of the univentricular heart was analyzed by the Tei index. Regional myocardial velocities and strain of the univentricular heart including the rudimentary right ventricle (RV) were quantified by tissue Doppler imaging. Intra-univentricular or intra left ventricular (LV) diastolic delay was measured from the difference of diastolic intervals (time to peak early diastolic velocity), measured at LV lateral wall and the rudimental RV wall in patients, or LV lateral wall and the ventricular septum in controls.

Results

Compared to the control group, patients after Fontan operation had significantly elevated Tei index (0.24 ± 0.02 vs. 0.41 ± 0.1, p < 0.001). On the other hand, the regional myocardial velocities and strains of the univentricular heart including the rudimentary RV were significantly reduced (p < 0.001). Among patients, there was a significant correlation between the Tei index of the univentricular ventricle and rudimentary RV strain (r = ?0.66, p = 0.01). The heart rate-corrected intra-univentricular diastolic delay was significantly prolonged among patients when compared to the intra-LV diastolic delay in controls (0.01 ± 0.9 vs. 1 ± 1.1, p = 0.005).

Conclusions

Myocardial dysfunctions and intra-univentricular diastolic asynchrony of the univentricular heart in patients after Fontan procedure are evident. The rudimentary RV in patients after Fontan procedure plays an important role in the determination of the global function of the univentricular heart.     

Oscillatory support for rapid frequency change processing in infants

Rapid auditory processing and auditory change detection abilities are crucial aspects of speech and language development, particularly in the first year of life. Animal models and adult studies suggest that oscillatory synchrony, and in particular low-frequency oscillations play key roles in this process. We hypothesize that infant perception of rapid pitch and timing changes is mediated, at least in part, by oscillatory mechanisms. Using event-related potentials (ERPs), source localization and time-frequency analysis of event-related oscillations (EROs), we examined the neural substrates of rapid auditory processing in 4-month-olds. During a standard oddball paradigm, infants listened to tone pairs with invariant standard (STD, 800–800 Hz) and variant deviant (DEV, 800–1200 Hz) pitch. STD and DEV tone pairs were first presented in a block with a short inter-stimulus interval (ISI) (Rapid Rate: 70 ms ISI), followed by a block of stimuli with a longer ISI (Control Rate: 300 ms ISI). Results showed greater ERP peak amplitude in response to the DEV tone in both conditions and later and larger peaks during Rapid Rate presentation, compared to the Control condition. Sources of neural activity, localized to right and left auditory regions, showed larger and faster activation in the right hemisphere for both rate conditions. Time-frequency analysis of the source activity revealed clusters of theta band enhancement to the DEV tone in right auditory cortex for both conditions. Left auditory activity was enhanced only during Rapid Rate presentation. These data suggest that local low-frequency oscillatory synchrony underlies rapid processing and can robustly index auditory perception in young infants. Furthermore, left hemisphere recruitment during rapid frequency change discrimination suggests a difference in the spectral and temporal resolution of right and left hemispheres at a very young age.     

Effect of natural gel product on bovine dentin erosion in vitro

Objective

To evaluate the efficacy of Neem (Azadirachta indica) experimental gel for the prevention of erosive wear on bovine dentin, in vitro.

Material and Methods

One hundred dentin blocks were allocated into 5 experimental groups (20 samples each): C (control group, without gel); CG (control group, only base gel); F (fluoride gel, 1.23% NaF; pH 4.1, Dentsply; Brazil); N (Neem gel, 10% neem extract; pH 4.1, manipulation); NF (Neem+fluoride gel, 10% Neem extract and 1.23% NaF; pH 4.1, manipulation). The blocks were stored in artificial saliva for 24 hours. After this, they were submitted to six alternating re- and demineralization cycles. The blocks were analyzed for wear (profilometry). The results were submitted to statistical analysis by ANOVA and Tukey tests (P<0.05).

Results

The mean wear (±SD, µm) was shown as follows in groups: C (13.09±0.99), CG (10.60±1.99), F (10.90±1.44), N (12.68±1.13) and NF (10.84±1.65). All gels showed some preventive action when compared with control group. However, significant differences were found only between Neem+fluoride gel and fluoride gel.

Conclusion

A single application of a neem-containing fluoride gel reduced dentin erosion, thus it is a possible alternative in reducing dental wear. Further research should investigate the action mechanism and the synergism between them.