Browsing by Author "Lai, Hsiu-Yun"

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PEGylation Site-Dependent Structural Heterogeneity Study of MonoPEGylated Human Parathyroid Hormone Fragment hPTH(1-34)
(2014-09-30)
Liu, Chih-Ying
;
Li, Xin
;
Chen, Wen-Yih
;
Chang, Li-Chiao
;
Chen, Yi-Fan
The structures of C- and N-terminally monoPEGylated human parathyroid hormone fragment hPTH(1-34) as well as their unmodified counterparts, poly(ethylene glycol) (PEG) and hPTH(1-34), have been studied by small-angle neutron scattering (SANS). The scattering results show that free hPTH(1-34) in 100 mM phosphate buffer (pH 7.4) aggregates into clusters. After conjugation with PEG, the PEG-peptide conjugates self-assemble into a supramolecular core-shell structure with a cylindrical shape. The PEG chains form a shell around the hPTH(1-34) core to shield hPTH(1-34) from the solvent. The detailed structural information on the self-assembled structures is extracted from SANS using a model of the cylindrical core with a shell of Gaussian chains attached to the core surface. On the basis of the data, because of the charge-dipole interactions between the conjugated PEG chain and the peptide, the conjugated PEG chain forms a more collapsed conformation compared to free PEG. Moreover, the size of the self-assembled structures formed by the C-terminally monoPEGylated hPTH(1-34) is about 3 times larger than that of the N-terminally monoPEGylated hPTH(1-34). The different aggregation numbers of the self-assembled structures, triggered by different PEGylation sites, are reported. These size discrepancies because of different PEGylation sites could potentially affect the pharmacokinetics of the hPTH(1-34) drug.
Single and dual antiplatelet therapy in elderly patients of medically managed myocardial infarction
(2018-04-05)
Lin, Ting-Tse
;
Lai, Hsiu-Yun
;
Chan, K. Arnold
;
Yang, Yen-Yun
;
Lai, Chao-Lun
Backgrounds: To examine the comparative effectiveness between dual and single antiplatelet therapies in real-world, medically managed elderly patients with acute myocardial infarction (AMI). Methods: This retrospective study identified very elderly (> 85 years) patients, who were medically managed, with their first AMI from the Taiwan National Health Insurance claims database from 2007 to 2010. Patients were classified as dual antiplatelet therapy (DAPT) group, aspirin only group and clopidogrel only group. Study outcomes included all-cause death, cardiovascular death and gastrointestinal bleeding. Treating DAPT group as the reference, we employed a multivariable Cox regression model to compare the relative risks of outcomes between 3 groups using pairwise comparison approach. Results: Among 1469 patients with incident ST-elevation myocardial infarction (STEMI, 14%) or non-STEMI (86%), 390 patients were prescribed DAPT, 549 aspirin only, and 530 clopidogrel only. After 9 months of follow-up, aspirin only group had similar risks of all-cause death (adjusted HR 1.21, 95% CI 0.77-1.89, p = 0.41), cardiovascular death (adjusted HR 1.16, 95% CI 0.66-2.04, p = 0.60) and gastrointestinal bleeding (adjusted HR 1.66, 95% CI 0.77-3.57, p = 0.20) in comparison with DAPT group. Clopidogrel users had a higher risk of all-cause death (adjusted HR 1.50, 95% CI 1.00-2.25, p = 0.049) but similar risks of cardiovascular death and gastrointestinal bleeding when compared with DAPT. Conclusions: Among very elderly patients who were medically managed after AMI, single antiplatelet therapy had comparable protective effect as DAPT. But clopidogrel only strategy was associated with a higher risk of all-cause death.