We previously developed a novel series
of vinyl sulfones as nuclear
factor erythroid 2-related factor 2 (Nrf2) activators with therapeutic
potential for Parkinson’s disease (PD). However, the previously
developed lead compound (1) exhibited undesirable druglike
properties. Here, we optimized vinyl sulfones by introducing nitrogen
heterocycles to improve druglike properties. Among the synthesized
compounds, 17e was the most promising drug candidate
with good druglike properties. Compound 17e showed superior
effects on Nrf2 activation in cell-based assays compared to compound 1 (17e: half-maximal effective concentration
(EC50) = 346 nM; 1: EC50 = 530
nM). Compound 17e was further confirmed to induce expression
of Nrf2-dependent antioxidant enzymes at both mRNA and protein levels.
In a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model
of PD, 17e significantly attenuated loss of tyrosine
hydroxylase-immunopositive dopaminergic neurons, suppressed microglial
activation, and alleviated PD-associated motor dysfunction. Thus, 17e is a novel Nrf2 activator with excellent druglike properties
and represents a potential therapeutic candidate for PD.
Poly(methylmethacrylate) (PMMA), poly(2-hydroxyethyl methacrylate (PHEMA), and poly(2-hydroxypropyl methacrylate) (PHPMA) were modified to improve the wettability by two techniques: plasma and plasma source ion implantation. The modified surfaces were characterized to investigate the dependence of the modification and hydrophobic recovery on the polymer structure. The differences obtained under optimal experiment conditions among the polymers were interpreted in terms of their polymer structures including the glass transition temperature. The surface free energy, calculated from the contact angle measurements, revealed that its polar component was a dominant factor in improving the wettability. The PSII treatment created more functional groups on the surface and extensively modified the polymer layer than the plasma treatment.
PurposeIn Korea, the results of bariatric surgery have not been compared with those of nonsurgical treatment. The purpose of this study was to evaluate the effectiveness and safety of bariatric surgery vs. conventional nonsurgical treatment in severely obese Koreans.MethodsIn this retrospective cohort study, we reviewed the medical charts of 261 consecutive subjects who underwent bariatric surgery and 224 subjects who were treated with weight control medication and lifestyle modification therapy between January 2008 and February 2011. Measures of clinical effectiveness, including change in weight (%) and comorbid diseases, and occurrence of complications, were investigated for 18 months after bariatric surgery.ResultsBody mass index (BMI) was higher in the surgery group than in the conventionally treated group (mean ± standard deviation, 39.0 ± 6.2 vs. 34.3 ± 3.8). Diabetes was more prevalent in the surgery group than in the conventionally treated group (39.1% vs. 12.9%). The change in weight (%) between baseline and 18 months posttreatment was significantly greater in the surgery group (22.6%) than in the conventional therapy group (6.7%). While 57%, 47%, and 84% of subjects recovered from diabetes, hypertension, and dyslipidemia, respectively, in the surgery group, 10%, 20%, and 24% of subjects recovered from these conditions in the conventional group. Fifty-one subjects (19.5%) in the surgery group reported 61 complications (23.4%).ConclusionBariatric surgery in Korea was significantly more effective than conventional treatment for weight loss and recovery from comorbidities such as diabetes, hypertension, and dyslipidemia, with a reasonable complication rate.
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