Design,Synthesis, and Molecular Docking of Some Novel Tacrine Based Cyclopentapyranopyridine- and Tetrahydropyranoquinoline-Kojic Acid Derivatives as Anti-Acetylcholinesterase Agents

A novel series of tacrine based cyclopentapyranopyridine- and tetrahydropyranoquinoline-kojic acid derivatives were designed, synthesized, and evaluated as anti-cholinesterase agents. The chemical structures of all target compounds were characterized by ¹H-NMR, ¹³C-NMR, and elemental analyses. The synthesized compounds mostly inhibited acetylcholinesterase enzyme (AChE) with IC₅₀ values of 4.18–48.71 μM rather than butyrylcholinesterase enzyme (BChE) with IC₅₀ values of >100 μM. Among them, cyclopentapyranopyridine-kojic acid derivatives showed slightly better AChE inhibitory activity compared to tetrahydropyranoquinoline-kojic acid. The compound 10-amino-2-(hydroxymethyl)-11-(4-isopropylphenyl)-7,8,9,11-tetrahydro-4H-cyclopenta[b]pyrano[2′,3′ : 5,6]pyrano[3,2-e]pyridin-4-one ( 6f ) bearing 4-isopropylphenyl moiety and cyclopentane ring exhibited the highest anti-AChE activity with IC₅₀ value of 4.18 μM. The kinetic study indicated that the compound 6f acts as a mixed inhibitor and the molecular docking studies also illustrated that the compound 6f binds to both the catalytic site (CS) and peripheral anionic site (PAS) of AChE. The compound 6f showed moderate neuroprotective properties against H₂O₂-induced cytotoxicity in PC12 cells. The theoretical ADME study also predicted good drug-likeness for the compound 6f . Based on these results, the compound 6f seems to be a very promising AChE inhibitor for the treatment of Alzheimer's disease.     

High-intensity interval training lowers blood pressure and improves apelin and NOx plasma levels in older treated hypertensive individuals

Hypertension is the major risk factor for cardiovascular diseases and is one of the primary causes of morbidity and mortality worldwide. Apelin levels and NO bioavailability are impaired in older hypertensive patients. Exercise is an effective intervention for treating hypertension. Our purpose was to evaluate the effect of high-intensity interval training on blood pressure, apelin, and NOx plasma levels in older treated hypertensive individuals. Thirty treated hypertensive subjects (61.70?±?5.78 years, 17 males, 13 females) were randomly divided into 6 weeks of high-intensity interval training (n?=?15) and control (n?=?15). The exercise training was conducted for three 35-min sessions a week (1.5-min interval at 85–90% of heart rate reserve [HRR] and 2 min active phase at 50–55% of HRR). Assessment of plasma apelin, nitrite/nitrate (NOx), and endothelin-1 (ET-1) was performed before and after the intervention. At the end of the study, apelin, and NOx plasma levels increased significantly in the high-intensity interval training (HIIT) group (P?=?0.021, P?=?0.003, respectively). Conversely, ET-1 plasma levels significantly decreased in the training group after the intervention (P?=?0.015). Moreover, there was a positive correlation between the change of plasma apelin and change of plasma NOx (r?=?0. 771, P?=?0.0008). In addition, there was a negative correlation between the change of plasma ET-1, change of plasma apelin (r?=???0.595, P?=?0.019), and variation of NOx (r?=???0.572, P?=?0.025). This study indicates that, by increasing of apelin and NOx plasma levels, HIIT may be effective in reducing blood pressure.     

Experimental study of the performance of a very small repetitive plasma focus device in different working conditions

SORENA-1 is a very small repetitive Mather-type plasma focus device (20 J) that can operate at frequencies up to 1 Hz. This device has been designed and constructed in the Plasma and Nuclear Fusion Research School of the Nuclear Science and Technology Research Institute of Iran. In this article, the structure of SORENA-1 is described and results of experiments with Ar, Ne, and D₂ working gases at several discharge voltages and initial pressures are presented and analyzed.     

Prevalence of accessory deep peroneal nerve in referred patients to an electrodiagnostic medicine clinic

Background

Variations in the branching of posterior cord are important during surgical approaches to the axilla and upper arm, administration of anesthetic blocks, interpreting effects of nervous compressions and in repair of plexus injuries. The patterns of branching show population differences. Data from the African population is scarce.

Objective

To describe the branching pattern of the posterior cord in a Kenyan population.

Materials and methods

Seventy-five brachial plexuses from 68 formalin fixed cadavers were explored by gross dissection. Origin and order of branching of the posterior cord was recorded. Representative photographs were then taken using a digital camera (Sony Cybershot ^R, W200, 7.2 Megapixels).

Results

Only 8 out of 75 (10.7%) posterior cords showed the classical branching pattern. Forty three (57.3%) lower subscapular, 8(10.3%) thoracodorsal and 8(10.3%) upper subscapular nerves came from the axillary nerve instead of directly from posterior cord. A new finding was that in 4(5.3%) and in 3(4%) the medial cutaneous nerves of the arm and forearm respectively originated from the posterior cord in contrast to their usual origin from the medial cord.

Conclusions

Majority of posterior cords in studied population display a wide range of variations. Anesthesiologists administering local anesthetic blocks, clinicians interpreting effects of nerve injuries of the upper limb and surgeons operating in the axilla should be aware of these patterns to avoid inadvertent injury. A wider study of the branching pattern of infraclavicular brachial plexus is recommended.     

Results of the Preliminary Experiments with a Miniaturized Plasma Focus Device

Plasma Physics Reports - In this article, a miniaturized Mather-type Plasma Focus (PF) device is presented. This device operates at a very low energy range (0.3–3 J). Here, the results of the...     

DARPin Ec1-LMWP protein scaffold in targeted delivery of siRNA molecules through EpCAM cancer stem cell marker

Molecular Biology Reports - This study is to investigate the binding ability of Designed Ankyrin Repeat Proteins type Ec1that was fused to Low Molecular Weight Protamine (DARPin Ec1-LMWP) protein...     

Dose Measurements in a 20-J Repetitive Plasma Focus

In this article, the results of X-ray dose measurements executed using thermoluminescent dosimeters in experiments with a very small (20 J) repetitive plasma focus device named SORENA-1 are presented and analyzed. The working gas in these experiments was Argon. Also, pinch formation in experiments with this device has been observed. This device has been designed and constructed in Plasma and Nuclear Fusion Research School of Nuclear Science and Technology Research Institute of Iran. From these results, it is concluded that we can do experiments with this device using Ar as working gas all over the working days of year, and a good symmetry for measured dose around the device has been seen.