Xuemei Feng

N-Acetylcysteine Protects Against Hypoxia Mimetic-Induced Autophagy by Targeting the HIF-1α Pathway in Retinal Ganglion Cells

Hypoxia-induced retinal ganglion cell (RGC) death has been proposed to be the critical event in the pathophysiology of glaucoma. Therefore, delaying or halting RGC degeneration, known as neuroprotection, is a novel and promising approach with potential clinical applications for treating glaucoma. In this study, we investigate hypoxia-induced cell death of RGCs and the underlying mechanisms of N-acetylcysteine (NAC) as a neuroprotectant. To establish a model for chemical hypoxia-induced cell death, RGC-5 cells were treated with the hypoxia mimetic cobalt chloride (CoCl2). Following CoCl2 exposure, significant levels of apoptotic and autophagic cell death were observed in RGC-5 cells, evidenced by lysosome dysfunction and autophagosome formation. Pretreating RGC-5 cells with NAC significantly counteracted the autophagic cell death. NAC-mediated neuroprotection was attributed to the direct scavenging of reactive oxygen species and was mediated by targeting the hypoxia-inducible factor-1α pathway via the BNIP3 and PI3K/Akt/mTOR pathways. These results provide insights into the degeneration of RGCs and present a potential clinical application for NAC as a neuroprotectant.

Activation of Muscarinic Receptors Protects against Retinal Neurons Damage and Optic Nerve Degeneration In Vitro and In Vivo Models

Muscarinic acetylcholine receptor agonist pilocarpine reduces intraocular pressure (IOP) of glaucoma mainly by stimulating ciliary muscle contraction and then increasing aqueous outflow. It is of our great interest to know whether pilocarpine has the additional properties of retinal neuroprotection independent of IOP lowering in vitro and in vivo models.

Preparation and evaluation of a novel delayed-onset sustained-release system of propranolol hydrochloride.

The objective of this work was to prepare and evaluate a new delayed‐onset sustained‐release system, comprising a sustained‐release core tablet with hydroxypropyl methylcellulose as polymer matrix and an ethylcellulose/Eudragit L coating capable of delaying the drug release. The sustained core containing propranolol hydrochloride as the model drug was prepared by granulate tableting and the polymer coating was applied in a computer‐controlled coating pan. The dissolution tests demonstrated that the in‐vitro drug release was pH‐dependent with sufficient gastric resistance, and the lag time (t10%) could be controlled by adjusting the coating level. Three dosage forms including commercial tablet, sustained‐release tablet and the delayed‐onset sustained‐release tablet were administrated to six beagle dogs and the plasma levels of propranolol hydrochloride were measured with high‐performance liquid chromatography. The delayed‐onset sustained‐release tablet had a lag time of 3.0 h in‐vitro and 3.5 h in‐vivo, and a tmax of 7.0 h. The relative bioavailability for delayed‐onset sustained‐release tablet was 96.98% compared with commercial tablets. The results indicate that the new propranolol delayed‐onset sustained‐release system could achieve a relatively constant drug release followed by a programmed lag time, and this may provide a promising drug delivery form for chronopharmacotherapy of certain cardiovascular diseases.

Quantitative determination of a novel enantiomeric tropane analog, (−)-satropane, in biological fluids using liquid chromatography/tandem mass spectrometry

A sensitive, accurate and precise liquid chromatography-tandem mass spectrometry method was developed for the determination of (-)-satropane (3alpha-paramethyl-benzenesulfonyloxy-6beta-acetoxy-tropane) in rabbit aqueous humor. Since (-)-satropane may be absorbed from the aqueous humour with resultant systemic side effects, the LC-MS/MS method was also evaluated for its applicability in analyzing plasma samples containing this compound. (-)-Satropane and phentolamine (the internal standard, represented as IS) were detected by multiple reaction monitoring using the transitions m/z 354-182 and 282-212, respectively. The calibration curve was linear over the ranges 2-500 and 5-1000 ng/mL, and the values of the lower limit of quantification were 2 and 5 ng/mL for the microdialysis dialysate and rat plasma samples, respectively. The intra-day and inter-day precision and accuracy were better than 8.6 and 6.00%, respectively, in both matrices investigated. The absolute recovery of the plasma samples was more than 76.30%. The average matrix effects of (-)-satropane were 91.72 and 83.05% in the microdialysis dialysate and plasma samples, respectively. The validated method was successfully applied to analyze (-)-satropane in microdialysis dialysate and rat plasma samples, and this assay has been used to quantify (-)-satropane in the pharmacokinetic and toxicokinetic studies in our laboratory.