Nimodipine rescues N-methyl-N-nitrosourea-induced retinal degeneration in rats.

BACKGROUND: That nimodipine (NMD) is potentially useful for ophthalmic treatment. However, the effect of NMD is unknown on retinal degenerative diseases. OBJECTIVE: The purpose of the present study was to investigate the effect of NMD on N-methyl-N-nitrosourea (MNU)-induced retinal degeneration (RD) and elucidate its possible mechanisms. MATERIALS AND METHODS: Morphological observation of NMD on MNU-induced RD was evaluated by light microscopy and electron microscopy. Nonenzymatic antioxidant glutathione (GSH) was measured by a colorimetric method. Transforming growth factor-beta (TGF-ß) was measured by enzyme-linked immunosorbent assay (ELISA). Telomerase was detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: The significantly protective effect of NMD on MNU-induced RD was demonstrated morphologically. NMD increased the content of GSH and decreased the level of TGF-ß in rat retina. RT-PCR analysis demonstrated that NMD treatment significantly decreased mRNA level of telomerase. CONCLUSION: These data suggest that NMD inhibit MNU-induced RD in rats. The expressions of TGF-ß, telomerase and GSH contents might partially contribute to its protective effects on MNU-induced RD.

Nimodipine inhibits N-methyl-N-nitrosourea-induced retinal photoreceptor apoptosis in vivo.

PURPOSE: The purpose of the present study was to investigate the effect of nimodipine (NMD), a calcium channel blocker, on N-methyl-N-nitrosourea (MNU)-induced retinal degeneration. MATERIALS AND METHODS: 60 mg/kg MNU was given intraperitoneally to 6-week-old female Sprague-Dawley rats, and NMD was injected intraperitoneally for up to 5 days after MNU. The effect of NMD was evaluated by electron microscopy and electroretinography (ERG). Proteins of Bax, Bcl-2, Caspase-3, and mitochondrial membrane potential (MMP) were analyzed with flow cytometry. The expressions of phosphodiesterase (PDE) and Caspase-3 were detected by reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: The apparent preservation of NMD to the photoreceptor cell was demonstrated by electron microscopy. After NMD treatment, both a- and b-waves of ERG were significantly higher compared with the control group, and had a protective effect on MNU-damaged retinal ERG. Flow cytometric assays showed that NMD decreased the level of Bax and Caspase-3 and increased the activity of Bcl-2 in retina. NMD significantly restored the mitochondrial membrane potential (MMP). RT-PCR analysis demonstrated that NMD treatment significantly decreased mRNA level of Caspase-3, and mRNA level of PDE was clearly upregulated. CONCLUSIONS: These data suggest that NMD may regulate the expressions of Bax, Bcl-2, Caspases-3, and PDE, and protection on the functions of retinal cell mitochondria inhibit MNU-induced photoreceptor cell apoptosis and protect retinal function in rats.

[Teaching experience in integrated course of human development and genetics].

Establishment of integrated course system in human development and genetics is an important part of course reformation, and the improvement of this system is achieved by integrating the content of course, stabilizing teaching force, building teaching materials and applying problem-based learning. Integrity-PBL teaching model is founded and proved to be feasible and effective by teaching practice. Therefore, it maybe play an important role in improving teaching effect and cultivating ability of students to analyse and solve problems.

Ellagic acid promotes Abeta42 fibrillization and inhibits Abeta42-induced neurotoxicity.

Smaller, soluble oligomers of beta-amyloid (Abeta) play a critical role in the pathogenesis of Alzheimer's disease (AD). Selective inhibition of Abeta oligomer formation provides an optimum target for AD therapy. Some polyphenols have potent anti-amyloidogenic activities and protect against Abeta neurotoxicity. Here, we tested the effects of ellagic acid (EA), a polyphenolic compound, on Abeta42 aggregation and neurotoxicity in vitro. EA promoted Abeta fibril formation and significant oligomer loss, contrary to previous results that polyphenols inhibited Abeta aggregation. The results of transmission electron microscopy (TEM) and Western blot displayed more fibrils in Abeta42 samples co-incubated with EA in earlier phases of aggregation. Consistent with the hypothesis that plaque formation may represent a protective mechanism in which the body sequesters toxic Abeta aggregates to render them harmless, our MTT results showed that EA could significantly reduce Abeta42-induced neurotoxicity toward SH-SY5Y cells. Taken together, our results suggest that EA, an active ingredient in many fruits and nuts, may have therapeutic potential in AD.