Mitochondrial Dependent Apoptosis: Ameliorative Effect of Flunarizine on Ischemia–Reperfusion of Celiac Artery-Induced Gastric Lesions in the Rat

Objectives  

Ischemia–reperfusion is a major event for induction of cellular apoptosis. Apoptosis is due to the activation of death receptor and/or mitochondrial pathways. Mitochondrial permeability transition pore opening is the cause of apoptosis. In our present study, we tried to evaluate the role of flunarizine in ischemia and reperfusion of celiac artery-induced gastric lesion in the rat.     

Synthesis of berberine-piperazine conjugates as potential antioxidant and cytotoxic agents

Piperazine derivatives bearing different electron-withdrawing and electron-donating functional groups were linked to the well-known isoquinoline alkaloid derivative, berberine via efficient organic transformations. The entire target berberine-based analogues were examined for their in vitro antioxidant potency using 2,2-diphenyl-1-picrylhydrazyl and 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid bioassays, and anticancer activities using sulforhodamine B assay against HeLa and CaSki cervical cancer cell lines in addition to the cytotoxicity using Madin-Darby canine kidney non-cancer cell lines and, ascorbic acid and berberine used as a control for antioxidant and anticancer activities, respectively. Bioassay results revealed that newer compounds were more active against CaSki and HeLa cell lines with therapeutic indices better than that of parent berberine and showed tolerable cytotoxicity to the normal cells. A final analogue 5a with 4-methylpiperazine substituent indicated most significant anticancer potency with a therapeutic index of 58.53 (HeLa) and 48.76 (CaSki), followed by those bearing meta-chloropiperazine rings with a therapeutic index of 41.83 (HeLa) and 47.35 (CaSki), respectively.In addition, newly synthesized analogues exerted a significant radical scavenging activity against 2,2′-azino-bis-3-ethylbenzthiazoline-6-sulphonic acid cation with IC₅₀ values of 8.917?µg/mL, and were good to moderate scavengers of 2,2-diphenyl-1-picrylhydrazyl radical with IC₅₀ values of 25.40?µg/mL. Synthesized compound was characterized using several techniques, fourier transform infrared spectroscopy, ¹H nuclear magnetic resonance, ¹³C nuclear magnetic resonance, mass spectroscopy and elemental (CHN) analyses.     

Effect of high‐frequency subthalamic neurostimulation on gait and freezing of gait in Parkinson's disease: a systematic review and meta‐analysis

The aim of this meta‐analysis was to summarize the short‐ and long‐term effects of bilateral deep brain stimulation of the subthalamic nucleus (STN‐DBS) on gait and freezing of gait (FOG) in Parkinson's disease and to detect predictors of post‐stimulation outcome. A comprehensive review of the literature was conducted up to October 2015 using Medline Ovid databases for studies analyzing the effect of bilateral STN‐DBS on FOG and/or gait. Sixteen studies with available data for the gait item (no. 29) of the Unified Parkinson's Disease Rating Scale (UPDRS) and six studies with the FOG item (no. 14) were included. Data were summarized for the following follow‐up periods: 6–15, 24–48 and >48 months. For the medication (Med)‐Off/stimulation(Stim)‐On condition compared with baseline Med‐Off, STN‐DBS significantly improved gait on average from 2.43 to 0.96, 2.53 to 1.31 and 2.56 to 1.40 points at 6–15, 24–48 and >48 months, respectively (P < 0.05). Pre‐operative levodopa responsiveness of UPDRS‐III and Med‐Off severity of gait were the predictors of this beneficial effect. STN‐DBS significantly improved FOG for the Med‐Off/Stim‐On condition compared with baseline on average from 2.26 to 0.82, 2.43 to 1.13 and 2.48 to 1.38 points at 6–15, 24–48 and >48 months, respectively (P < 0.05). There was no significant effect in the Med‐On/Stim‐On condition. This meta‐analysis showed a robust improvement of gait and FOG by STN‐DBS for more than 4 years in the Med‐Off/Stim‐On condition. No beneficial effect was found for the On state of medication. Pre‐operative levodopa responsiveness of global motor performance (UPDRS‐III) is the strongest predictor of the effect of deep brain stimulation on gait.     

Ameliorative effects of Ocimum sanctum in sciatic nerve transection-induced neuropathy in rats

Objectives

The present study was aimed at investigating the ameliorative effect of Ocimum sanctum in sciatic nerve transection (axotomy)-induced peripheral neuropathy in rats.

Materials and methods

Sciatic nerve transection-induced axonal degeneration was assessed histopathologically. Paw pressure, Von Frey Hair, tail cold-hyperalgesia, motor in-coordination tests were performed to assess the extent of neuropathy. Biochemical estimations of thiobarbituric acid reactive species (TBARS), reduced glutathione (GSH), and total calcium levels were also performed. Methanolic extract of Ocimum sanctum at different doses (50, 100 and 200 mg/kg p.o.) was administered for 10 consecutive days starting from the day of surgery.

Results

Administration of Ocimum sanctum attenuated sciatic nerve transection-induced axonal degeneration, reduction of nociceptive threshold and motor in-coordination. Moreover, it also attenuated axotomy-induced rise in TBARS, total calcium and decrease in GSH levels in a dose-dependent manner.

Conclusion

Anti-oxidant and calcium attenuating actions may be responsible for observed ameliorative effects of Ocimum sanctum in axotomy-induced neuropathy.     

Metabolic and amyloid PET network reorganization in Alzheimer’s disease: differential patterns and partial volume effects

Brain Imaging and Behavior - Alzheimer’s disease (AD) is a neurodegenerative disorder, considered a disconnection syndrome with regional molecular pattern abnormalities quantifiable by the...     

Determination of Buckling Behavior of Web-Stiffened Cold-Formed Steel Built-Up Column under Axial Compression

The practice of utilizing cold-drawn steel for structural and non-structural elements has expanded nowadays due to it being lighter in weight, economic section, desirable in fabrication, and its preferred post-buckling behavior over hot rolled sections. The cold-drawn steel section back to the back-lipped channel section has a wide application as a structural member. The fasteners are provided at regular intervals for the long-span structure to prevent individual failures. This study is concerned with the inadequacy of research addressing the behavior of built-up columns. The relevant built-up column section is chosen based on the AISI-S100:2007 specification. Thirty-six specimens were designed and tested by varying web, flange, lip dimensions, spacing between the chords, and battened width experimentally subjected to an axial compression. Comparing 36 experimentally buckled specimens with the model generated by Finite Element Method accompanied with ASI-recommended two direct strength methods (DSMs). The DSM comprises the step-by-step procedure incorporated with the elastic, critical, and global distortional interaction. Based on the performed reliability analysis, such as the experimental, analytical, and theoretical studies, the failure load, buckling mode, the economic section, and design rules were proposed. Four suitable sections were selected from the proposal, and the validation study was carried out. From the validation study, experimental values were found to be 1.072 times the FEM values, and DSM values were found to be 0.97 times the FEM values. Based on the significant findings of this study, the proposed design recommendation and the corrected value for DSM are suitable for designing back-to-back stiffened columns.