Interferon-lambda 3 and 4 Polymorphisms Increase Sustained Virological Responses and Regulate Innate Immunity in Antiviral Therapy With Pegylated Interferon-Alpha.

Sustained virologic response (SVR) in chronic hepatitis C (CHC) treatment denotes that the host genetics controls the immune response and unequivocally contribute to viral clearance or disease severity. In this context, single nucleotide polymorphisms (SNPs) in the locus of interferon lambda 3 and 4 genes (IFNL3/4) have been important genetic markers of responsiveness to CHC as prognostic markers for the pegylated-Interferon-alpha/ribavirin (Peg-IFN-α/RBV). Here, we analyzed 12 SNPs at the IFNL3/4 region in 740 treatment-naïve patients with CHC infected with hepatitis C virus (HCV) genotypes 1, 2, or 3 treated with Peg-IFN-α/RBV. Individually, rs12979860-CC, rs8109886-CC, or rs8099917-TT were predictive markers of SVR, while rs12979860-CC demonstrated the stronger effect. Besides, the genotypic combination of these three predictors' genotypes, CC/CC/TT, increased the rate of SVR. Serum levels of cytokines and gene expression analysis on the genes IFNL3, IFNL4, IFNA1, and some of the IFN-stimulated genes (ISGs) were measured in a subgroup of 24 treated patients and 24 healthy volunteers. An antagonist effect was highlighted between the expression of IFNL3/4 and IFNA1 mRNA among patients. Besides, a prominent production of the pro-inflammatory chemokines CCL4 and CXCL10 was observed at a 12-week treatment follow-up. Lower serum levels of these chemokines were detected in patients with an rs12979860-CC genotype associated with the better treatment outcome. Also, lower expression levels of the IFI6, IFI16, IRF9 genes were observed among rs12979860-CC individuals. In conclusion, a combination of the genotypes at the IFNL3/4 locus can act as a better marker for the prognosis for virological responses in an admixed Brazilian population presenting the modulating effect over innate immunity and inflammation that are controlling the outcome of the viral infection, but also other infectious diseases. This study is registered on the ClinicalTrials.gov platform (accession number NCT01889849 and NCT01623336).

Sequential bone healing of immediately loaded mini-implants: histomorphometric and fluorescence analysis.

INTRODUCTION: Mini-implants are often immediately loaded for orthodontic treatment; however, changes in interfacial tissues caused by early loading and its effects might compromise the mini-implant's function. The purpose of this study was to compare the healing of interfacial tissues 1, 4, and 12 weeks after the placement of titanium-alloy mini-implants in New Zealand rabbits; some of the implants were loaded immediately and others were left unloaded. METHODS: Eighteen animals were used in the experiment. Each received 4 titanium grade 5 mini-implants (2.0 x 6.0 mm), 2 of which were immediately loaded with 1 N of force. Tissue healing was verified at 1, 4, and 12 weeks after placement. Four different fluorescent molecules were injected into the rabbits to label calcium deposition. After the rabbits were killed, mineralized bone samples with the mini-implants were removed, fixed, cut, stained, and observed with bright-field, polarized, and fluorescence microscopy. RESULTS: After 12 weeks of healing, higher bone contact and bone area were observed than after 1 or 4 weeks, regardless of loading. Differences between the loaded and unloaded groups were not observed (P <0.05) at 1 and 4 weeks. The bone deposition rate was higher in the loaded group. CONCLUSIONS: The 1-N immediate force application did not compromise bone formation around mini-implants.

Sequential bone healing of immediately loaded mini-implants.

INTRODUCTION: The relatively small size and the ability to load mini-implants without delay are important changes in the simplification of bone rigid anchorage. The purpose of this study was to analyze interfacial healing 1, 4, and 12 weeks after the placment of titanium mini-implants in New Zealand rabbits by removal torque test (RTT) and scanning electron microscopy (SEM). METHODS: Eighteen animals were used in the experiment, in which 72 titanium grade 5 mini-implants 2.0 mm in diameter and 6.0 mm long, were placed. Each animal received 4 mini-implants; 2 were immediately loaded with 1 N. RESULTS: The RTT means for the unloaded mini-implants at 1, 4, and 12 weeks were 15.2 +/- 4.2 N mm (n = 5), 13.1 +/- 5.7 N mm (n = 5), and 54.4 +/- 12.8 N mm (n = 4), respectively. The loaded groups had means of 12.7 +/- 5.1 N mm (n = 4), 11.1 +/- 5.4 N mm (n = 4), and 32.9 +/- 12.8 N mm (n = 5) for the same healing periods, respectively. The statistical evaluation indicated significance in the comparison between loaded and unloaded 12-week groups (P <0.05). SEM analysis in the loaded group showed the formation of less fibrous interfacial tissue after 4 weeks and more lamellar appearance after 12 weeks. CONCLUSIONS: The immediate 1-N load did not cause significant changes in the fixation of the mini-implants after 1 and 4 weeks of bone healing. Nevertheless, after 12 weeks, the loaded group had significantly lower RTT values than the unloaded group without compromising the stability of the mini-implants (P <0.05).