Long-term in vitro degradation behaviour of Fe and Fe/Mg2Si composites for biodegradable implant applications.

The major drawback of Fe-based materials for biodegradable implant applications is their slow degradation rate. Addition of second phase particles into the Fe matrix can increase the degradation rate at the beginning of the corrosion process. However, so far, there is neither quantitative data on in vitro degradation nor direct experimental evidence for long-term dissolution of Fe-based biodegradable composites. Here, a series of immersion tests at different exposure intervals (20, 50 and 100 days) to modified Hanks' solution were performed to study the degradation behavior of Fe and Fe/Mg2Si composites prepared by different powder metallurgy techniques. The results revealed the role of Mg2Si in the composition and stability of the protective films formed during the static corrosion experiments. Fe/Mg2Si composites showed higher degradation rates than those of pure Fe at all stages of immersion. Degradation rates at distinct exposure intervals strongly depended on the composition and stability of formed oxide, hydroxide, carbonate and phosphate protective films on the degraded surfaces. The release of Fe ions into the solution at later stages of the experiment was limited due to the barrier effect of the insoluble deposit. This fundamental study provided a basis for the processes of protective film formation in modified Hanks' solution, which enables a detailed identification of its characteristic features.

Synthesis, mechanical properties and corrosion behavior of powder metallurgy processed Fe/Mg2Si composites for biodegradable implant applications.

Recently, Fe and Fe-based alloys have shown their potential as degradable materials for biomedical applications. Nevertheless, the slow corrosion rate limits their performance in certain situations. The shift to iron matrix composites represents a possible approach, not only to improve the mechanical properties, but also to accelerate and tune the corrosion rate in a physiological environment. In this work, Fe-based composites reinforced by Mg2Si particles were proposed. The initial powders were prepared by different combinations of mixing and milling processes, and finally consolidated by hot rolling. The influence of the microstructure on mechanical properties and corrosion behavior of Fe/Mg2Si was investigated. Scanning electron microscopy and X-ray diffraction were used for the assessment of the composite structure. Tensile and hardness tests were performed to characterize the mechanical properties. Potentiodynamic and static corrosion tests were carried out to investigate the corrosion behavior in a pseudo-physiological environment. Samples with smaller Mg2Si particles showed a more homogenous distribution of the reinforcement. Yield and ultimate tensile strength increased when compared to those of pure Fe (from 400MPa and 416MPa to 523MPa and 630MPa, respectively). Electrochemical measurements and immersion tests indicated that the addition of Mg2Si could increase the corrosion rate of Fe even twice (from 0.14 to 0.28mm·year-1). It was found that the preparation method of the initial composite powders played a major role in the corrosion process as well as in the corrosion mechanism of the final composite.

A randomized trial of prolonged high dose of interferon plus ribavirin for hepatitis C patients nonresponders to interferon alone.

Retreatment of chronic hepatitis C patients nonresponders to interferon (IFN) alone with the standard dose of IFN [3 million units (MU) thrice weekly (TIW)] plus ribavirin for 24 weeks has yielded low sustained virological response (SVR), averaging 8%. The aim of the present, open-labelled, randomized study was to evaluate the efficacy of IFN induction therapy followed by prolonged high dose of IFN plus ribavirin in nonresponders. One hundred and fifty-one patients were randomized to receive 5 MU daily of IFN alfa-2b (group 1, n = 73) or 5 MU TIW of IFN alfa 2b (group 2, n = 78) for 4 weeks followed by IFN (5 MU TIW) plus ribavirin (1000/1200 mg/daily) for 48 weeks in both groups. In an intention-to-treat analysis, the sustained virological response (SVR) at 24-week follow-up was 33 and 23% for group 1 and 2, respectively (P = 0.17). The overall SVR was 52 and 18% in patients with genotype 2/3 and 1/4, respectively. Among genotype 1/4 patients the SVR was 29 and 11% for age younger or older than 40 years. Compared with genotype 2/3 patients, the risk (95% confidence interval) of nonresponse to retreatment was 3.0-fold (1.17-8.0) in younger genotype 1/4 patients and 8.4-fold (3.0-23.29) in older genotype 1/4 patients. In conclusion these results suggest that retreatment with a reinforced regimen should be focused in nonresponder genotype 2/3 patients and younger genotype 1/4 patients, who are most likely to benefit. Induction therapy does not improve SVR.

Efficacy of prolonged 5 million units of interferon in combination with ribavirin for relapser patients with chronic hepatitis C.

summary. Retreatment of relapser patients with chronic hepatitis C with the standard dose of interferon (IFN) of 3 million units (MU) thrice weekly (tiw) plus ribavirin for 24 weeks achieves a sustained response in 30 and 73% of patients with genotype 1 and 2 or 3, respectively. The aim of this study was to evaluate the efficacy and safety of IFN alpha-2b induction therapy, followed by prolonged treatment with a high dose of IFN alpha-2b plus ribavirin in relapser patients. A total of 119 patients were randomized to receive IFN alpha-2b 5 MU daily (Group A: 59 patients) or IFN alpha-2b 5 MU tiw (Group B: 60 patients) for 4 weeks followed by IFN (5 MU tiw) and ribavirin (1000-1200 mg/day) for 48 weeks in both groups. The primary end point was hepatitis C virus (HCV)-RNA clearance at week 24 after the end of treatment. A sustained virological response (SVR) was achieved in 68 and 60% of Group A and B patients, respectively (P = 0.37). Logistic regression analysis identified genotype 2 or 3 as the only independent factor associated with response, whereas induction regimen and baseline viraemia levels did not affect the response. The overall SVR was 53 and 72% in patients with genotype 1 or 4 and 2 or 3, respectively. In conclusion, induction IFN therapy does not enhance the SVR to a 48-week combination therapy. Our study suggests that relapsed patients with genotype 1 or 4 may achieve significant response rates of approximately 50%, if retreated with 5 MU tiw IFN plus ribavirin for 48 weeks.

125I-Antisauvagine-30: a novel and specific high-affinity radioligand for the characterization of corticotropin-releasing factor type 2 receptors.

Corticotropin-releasing factor (CRF) receptors type 1 (CRF(1)) and type 2 (CRF(2)) differ from each other in their pharmacological properties. The human and ovine CRF versions bind to CRF(1) receptors with significantly higher affinity than to CRF(2) receptors. Recently antisauvagine-30, an N-terminally truncated version of the CRF analog sauvagine, was characterized as a specific antagonist to mouse CRF(2B). We have synthesized the radiolabeled version (125)I-antisauvagine-30 and tested it for its affinity at human CRF(1) (hCRF(1)), hCRF(2A), Xenopus CRF(1) (xCRF(1)) and xCRF(2) receptors. In control binding studies (125)I-labeled hCRF, sauvagine and astressin were also bound to these receptors. (125)I-antisauvagine-30 exclusively bound to hCRF(2A) and xCRF(2) but not to hCRF(1) and xCRF(1) receptors. (125)I-antisauvagine-30 binding to hCRF(2A) and xCRF(2) receptors was saturable and of high affinity (hCRF(2A): K(d)=125 pM; xCRF(2): K(d)=1.1 nM). In displacement binding experiments using (125)I-antisauvagine-30 as radioligand several CRF analogs bound to hCRF(2A) and xCRF(2) receptors with similar rank orders as reported with other CRF radioligands. Finally, preliminary studies using (125)I-antisauvagine-30 binding to membrane homogenates prepared from different rat brain structures showed that the peptide bound specifically to brain areas expressing CRF(2) receptors. These data demonstrate that (125)I-antisauvagine-30 is the first high-affinity ligand to specifically label CRF(2) receptors.