一、論文分享
- 題目：
Telbivudine plus pegylated interferon alfa-2a in a randomized study in chronic hepatitis B is associated with an unexpected high rate of peripheral neuropathy
- 作者：Marcellin P, Wursthorn K, Wedemeyer H, Chuang WL, Lau G, Avila C, Peng CY, Gane E, Lim SG, Fainboim H, Foster GR, Safadi R, Rizzetto M, Manns M, Bao W, Trylesinski A, Naoumov N Hepatol. 2015 Jan;62(1):41-7. doi: 10.1016/j.jhep.2014.08.021. Epub 2014 Aug 23
- 摘要：
BACKGROUND & AIMS: This study investigated the antiviral efficacy and safety of telbivudine in combination with pegylated interferon (PegIFN) alpha-2a in chronic hepatitis B (CHB) patients.METHODS: This was a randomized, open-label, multicentre study, in treatment-naïve patients with HBeAg-positive CHB, comparing the efficacy and safety of telbivudine in combination with PegIFN alpha-2a with telbivudine monotherapy and PegIFN alpha-2a monotherapy. The study was terminated early due to increased rates of peripheral neuropathy in the combination-therapy group.
RESULTS: Of the 159 patients randomized (from 300 planned) 50 were assigned to combination therapy, 55 to telbivudine, 54 to PegIFN, and 110 (18, 49, and 43, respectively) reached week 24. Peripheral neuropathy occurred in 7/50, 1/54, and 0/54 patients in the three groups of safety populations, respectively. No relationship between the occurrence of peripheral neuropathy and other variables (e.g., pharmacokinetic data, treatment efficacy, ALT levels, creatine kinase elevations) were observed. At week 24, undetectable HBV DNA (<300 copies/ml) was achieved by 71% (12/17), 35% (17/48), and 7% (3/42) of patients, with available data receiving combination therapy, telbivudine monotherapy and PegIFN monotherapy, respectively (p = 0.022 for combination therapy vs. telbivudine; p<0.0001 for combination therapy vs. PegIFN).
CONCLUSIONS: Combination therapy carried an increased risk of peripheral neuropathy. Despite the rapid and profound reductions in HBV DNA levels, combination therapy with telbivudine and PegIFN should not be used.
- 題目：
Imaging and Chemotherapeutic Comparisons of Iron Oxide Nanoparticles Chemically and Physically Coated with Poly(ethylene glycol)-b-Poly(ε-caprolactone)-g-Poly(acrylic acid)
- 作者：Chen, Guo-Jing; Hsu, Chin; Ke, Jyun-Han; Wang, Li-Fang Journal of Biomedical Nanotechnology, Volume 11, Number 6, June 2015, pp. 951-963(13)
- 摘要：
We designed a new copolymer, poly(ethylene glycol)-block-poly(ε-caprolactone)-graft-poly(acrylic acid) (PAA-PEC), which could be chemically and physically coated onto iron oxide (Fe3O4) nanoparticles for theranostic applications. The chemically PAA-PEC-coated Fe3O4 nanoparticles (PAA-PEC-IO) were prepared using the carboxylic groups of PAA-PEC to bind the Fe3O4 nanoparticles during a co-precipitation reaction. Because of the amphiphilic properties of PAA-PEC, the compound self-assembled into a core–shell structure. The hydrophobic oleic acid-coated Fe3O4 nanoparticles could then be physically encapsulated inside the hydrophobic core of PAA-PEC (PAA-PEC-OA-IO) using an emulsion technique. A similar amount of iron content was controlled in both the PAA-PEC-IO and PAA-PEC-OA-IO (∼23%). The particle diameters, morphologies, superparamagnetism, drug loading efficiency, and transversal relaxivity (r 2) were studied and compared between the two magnetic nanoparticles. All results displayed the chemically-synthesized PAA-PEC-IO nanoparticles had higher potential than did the physically-synthesized PAA-PEC-OA-IO as an MRI contrast agent and a drug delivery carrier. Rodamine123-linked PAA-PEC-IO (PAA-PEC-IO-Rh123) was used as a molecular probe. Flow cytometric diagrams indicated that cellular internalization of PAA-PEC-IO occurred primarily through clathrin-mediated endocytosis.