Dual Beneficial Effects of (-)-Epigallocatechin-3-Gallate on Levodopa Methylation and Hippocampal Neurodegeneration: In Vitro and In Vivo Studies

A combination of levodopa (L-DOPA) and carbidopa is the most commonly-used treatment for symptom management in Parkinson's disease. Studies have shown that concomitant use of a COMT inhibitor is highly beneficial in controlling the wearing-off phenomenon by improving L-DOPA bioavailability as well as brain entry. The present study sought to determine whether (-)-epigallocatechin-3-gallate (EGCG), a common tea polyphenol, can serve as a naturally-occurring COMT inhibitor that also possesses neuroprotective actions.Using both in vitro and in vivo models, we investigated the modulating effects of EGCG on L-DOPA methylation as well as on chemically induced oxidative neuronal damage and degeneration. EGCG strongly inhibited human liver COMT-mediated O-methylation of L-DOPA in a concentration-dependent manner in vitro, with an average IC50 of 0.36 microM. Oral administration of EGCG moderately lowered the accumulation of 3-O-methyldopa in the plasma and striatum of rats treated with L-DOPA+carbidopa. In addition, EGCG also reduced glutamate-induced oxidative cytotoxicity in cultured HT22 mouse hippocampal neuronal cells through inactivation of the nuclear factor kappaB-signaling pathway. Under in vivo conditions, administration of EGCG exerted a strong protective effect against kainic acid-induced oxidative neuronal death in the hippocampus of rats.These observations suggest that oral administration of EGCG may have significant beneficial effects in Parkinson's patients treated with L-DOPA and carbidopa by exerting a modest inhibition of L-DOPA methylation plus a strong neuroprotection against oxidative damage and degeneration

Copyright Legislative Impunity? How Copyright Term Extensions Violate Freedom of Expression

With the global trend of harmonizing intellectual property rights, there is enormous pressure on Canada to adopt a maximalist approach to copyright protection. The purpose of this paper is to assess the constitutionality of the copyright extensions for sound recordings and performances found within the Economic Action Plan 2015 Act. Although Canadian courts have been reluctant in the past to consider the effects of copyright law on freedom of expression, the time is now ripe for the courts to assert their authority under the constitution. This paper demonstrates that copyright law is indeed in conflict with freedom of expression and that any time the legislature amends or imposes new burdens on expression, the government must justify those actions. In the case of the twenty-year term extension for sound recordings and performances, a constitutional analysis reveals that the law is disproportionate and cannot be saved under s.1 of the Charter.LL.M

Antibiotic Resistance in Neisseria gonorrhoeae: Challenges in Research and Treatment

Gonococcal infection caused by the Gram-negative bacteria Neisseria gonorrhoeae is one of the most common sexually transmitted infections (STIs) worldwide [...