Different administration schedules of darbepoetin alfa affect oxidized and reduced glutathione levels to a similar extent in 5/6 nephrectomized rats

Background

The development of erythropoiesis-stimulating agents (ESAs) with extended serum half-lives has allowed marked prolongation of the administration intervals. The level of oxidative stress is increased in chronic kidney disease, and is reportedly decreased after long-term ESA treatment. However, the effect of different dosing regimens of ESAs on oxidative stress has not been elucidated.

Methods

Five-sixths nephrectomized (NX) rats received either 0.4 μg/kg darbepoetin alfa (DA) weekly or 0.8 μg/kg DA fortnightly between weeks 4 and 10. NX animals receiving saline and a sham-operated (SHAM) group served as controls. The levels of oxidized and reduced glutathione (GSSG, GSH) were followed from blood samples drawn fortnightly.

Results

During the follow-up, the ratios GSSG/GSH showed similar trends in both DA groups, levels being significantly lower than those in the SHAM group at weeks 8 and 10. GSSG levels were lower than the baseline throughout the study in all groups except for NX controls. The GSH levels were increased in all three NX groups (weeks 6–10) compared with both the baseline and the SHAM group

Conclusion

Our results suggest that the extent of oxidative stress is similar in response to different dosing regimens of DA in 5/6 NX rats when comparable hemoglobin levels are maintained. These findings remain to be confirmed in chronic kidney disease patients.     

Influence of exposure time to saliva and antioxidant treatment on bond strength to enamel after tooth bleaching: an in situ study

Objectives

This study evaluated the influence of different exposure times to saliva in situ in comparison with an antioxidant treatment on composite resin bond strength to human enamel restored after tooth bleaching.

Material and Methods

Forty human teeth specimens measuring 5x5 mm were prepared and randomly allocated into 5 groups with 8 specimens each: Gct (control group, restored on unbleached enamel); Gbl (restored immediately after bleaching); Gsa (bleached, treated with 10% sodium ascorbate gel for 60 min and restored); G7d (bleached, exposed to saliva in situ for 7 days and restored); and G14d (bleached, exposed to saliva in situ for 14 days and restored). Restored samples were cut into 0.8 mm² sticks that were tested in microtensile. Specimens were microscopically analyzed and failure modes were classified as adhesive, cohesive, or mixed. Pretest and cohesive failures were not considered in the statistical analysis, which was performed with one-way ANOVA and Tukey''s post-hoc test (α=0.05), with the dental specimen considered as the experimental unit.

Results

Mean bond strength results found for Gbl in comparison with Gct indicated that bleaching significantly reduced enamel adhesiveness (P<0.01). However, no statistically significant differences were found between Gct, Gsa and G7d (P>0.05). Bond strength found for G14d was significantly higher than for Gsa (P<0.01). Fractures modes were predominantly of a mixed type.

Conclusions

Bonding strength to bleached enamel was immediately restored with the application of sodium ascorbate and exposure to human saliva in situ for at least 7 days. Best results were obtained with exposure to human saliva in situ for 14 days. Treatment with sodium ascorbate gel for 60 min may be recommended in cases patients cannot wait for at least 7 days for adhesive techniques to be performed.     

Progression of Aortic Regurgitation After Different Repair Techniques for Congenital Aortic Valve Stenosis

We sought to characterize the incidence of AR progression and determine risk factors for AR progression in a consecutive series of infants and children after surgical correction of congenital aortic valvular and supravalvular stenosis. N = 30 patients underwent repair of the aortic valve for isolated congenital aortic valve stenosis (n = 14, 47 %) or combined with aortic regurgitation (AR, n = 16, 53 %). N = 27 (90 %) had a valvular and n = 3 patients (10 %) presented with supravalvular pathology of their aortic valve. In n = 16 patients (53 %) a bicuspid and in n = 2 (6 %) patients, a unicuspid valve was present. Comparative survival was analyzed using the Cox model and log-rank calculations. Log-rank calculations were performed for variables reaching statistical significance in order to identify differences in survival between groups. Commissurotomy was performed in n = 20 patients, patch implantation in n = 4, cusp shaving in n = 8, cusp prolapse correction in n = 3, and cusp augmentation in n = 4 patients. In patients with combined dysfunction and preoperative AR, AR was successfully reduced by the initial procedure, and postoperatively the overall median AR grade was 1+ (range 0–2.5+, p = 0.001, for AR reduction among patients with any grade of preoperative AR). By the time of follow-up echocardiography, the median AR grade had significantly progressed toward 1.5+ (p = 0.004). At the time of mid-term follow-up at 3.2 years, none of the patients had moderate or severe AR grades >2.5+. Patients with a monocuspid aortic valve and patients who had some kind of patch implantation into their cusps or commissures or shaving of thickened cusps were more likely to present with progression of aortic regurgitation. Monocuspid aortic valve and patch implantation, as well as cusp shaving, are probably linked to AR progression. The standard procedure of commissurotomy results in an absolute rate of AR progression of 40 % over a medium-term follow-up period.     

Rate of recurrence and malignant transformation in 88 cases with inverted papilloma between 1998–2008

Conclusions The recurrence rate of IP in the current study is comparable to international and national studies. When the primary tumour was located in the frontal or the sphenoid sinus, the tumour seemed more likely to recur. Some recurrences were more than 2 years after primary surgery, suggesting continued need for long-term follow-up. The rate of malignant transformation in inverted papilloma cases has not changed in Denmark.

Objectives Inverted papillomas are benign tumours located in the nasal cavity and paranasal sinuses. They are known for their tendency to recur after surgery and show invasive growth, causing bone remodulation and the association with malignant transformation. The introduction of endoscopic sinus surgery and computer aided sinus surgery over the last decades has made this tumour more approachable with less cosmetic and functional damage. The objective of this study is to establish whether the recurrence rate and the rate of malignant transformation of IP have changed with the application of these new techniques.

Method A retrospective study between 1998–2008 including 88 cases with inverted papilloma.

Results In total, 25.3% had recurrence. Combined surgical approach with endoscope/open approach had the lowest rate of recurrence. A malignant transformation in the postoperative histological examination was found in 8.9%.