Tag Archives: Obeticholic Acid

It is suggested that effect size

It is suggested that effect size of this SNP is greater in males. Indeed, sexual differences in the regulation of serum UA levels have been reported. Obesity is often accompanied by hyperuricemia, but few studies have addressed the association between obesity and genetic variants involved in UA metabolism. The degree of association between ABCG2 rs2231142 SNP and gout risk has been found to vary with ethnicity. In this study, we examined whether association between the ABCG2 SNPs and UA levels in a Taiwanese cohort is differentially regulated by sex and obesity.

Materials and methods

Results

Discussion
We confirmed association of the SNP rs2231142 with UA levels and hyperuricemia in a Taiwanese cohort, and found it predominantly in males. Furthermore, obesity alone determined serum UA levels regardless of ABCG2 genotypes or sex, and we were the first to find an association between the rs2231142-A allele and hyperuricemia in obese patients.
A previous study shows that serum UA concentration has a 63% heritability. Indeed, a meta-analysis identifies ABCG2 among nine loci associated with UA concentration. In these studies, rs2231142 is the only SNP consistently associated with both hyperuricemia and gout. We confirmed the association with hyperuricemia except in nonobese females.
Previous studies show substantial interaction between genotypes and sex on UA levels. For instance, rs2231142 is consistently associated with UA concentration and gout in males. Our data showed a similar interaction, as we found significant association between rs2231142 and UA levels in males.
We found significant association between rs2231142 and hyperuricemia in obese patients. In a mouse model of obesity, concentration of both ABCG2 and urate Obeticholic Acid transporter URAT1 increases significantly, suggesting a link between enhanced urate reabsorption and obesity-associated hyperuricemia. Although we did not measure ABCG2 or URAT1 concentration, UA concentration was higher in obese patients and was further enhanced in those carrying the rs2231142-A allele. We hypothesized that obesity readily reveals effect of rs2231142 on hyperuricemia.
We uncovered an extra layer of interaction between sex, obesity, and rs2231142 on UA levels. Our data showed rs2231142-A was not associated with UA levels in nonobese females. This difference might be due to specific physiological characteristics of the nonobese females other than that of estrogen, because it has been reported that estrogen does not increase renal clearance of serum UA in adult women. Regarding the female hormonal effect on UA levels, we did not observe significant differences between premenopausal and menopausal female subgroups (Supplementary Table 1). Alternatively, nonobesity may have ameliorated hyperuricemia in rs2231142-A-carrying females by compensating for reduced ABCG2 activities. Whether it is due to metabolic or additional hormonal effect awaits further investigation, and a larger sample size is needed to clarify the role of sex hormones on UA levels and hyperuricemia in female patients.

Limitation
Because of the relatively small sample size and high minor allele frequency of rs2231142 in this study (Supplementary Table 2), it might have had limited power to detect associations between rs2231142 and UA. Still, we were able to validate our results independently using multiple regressions adjusted for confounding factors (Supplementary Table 3). In addition, we also validated our results using multiple testing corrections including full scan permutations (p = 0.001 for 1000 permutations), Bonferroni adjustment and false discovery rate (FDR) calculations (rs2231142-C allele; both regression Bonferroni P and regression FDR = 5.7 × 10−4), thus strengthening the conclusion that rs2231142 is indeed associated with serum UA levels.

Conclusion
A reduction-of-function SNP rs2231142 in the ABCG2 gene is associated with hyperuricemia in a Taiwanese cohort. The genetic determinants Obeticholic Acid for hyperuricemia differ according to sex and obesity status. The rs2231142-A allele has significantly stronger association with hyperuricemia in male and obese patients.

Obeticholic Acid The zirconia substrate was not sandblasted

The zirconia substrate was not sandblasted before coating or infiltration as performed in previous studies [23], [24] and [25]; this was to exclude further variability, but assess only the potential effects of proposed treatments. The need for sandblasting prior to usage of organo-metallic precursors might be considered a drawback of the technique once it has been reported that air-abrasion could affect long-term reliability of oxide ceramics [26].
Overall, INF method attained lower initial bonding potential compared to COA method. These outcomes might be attributed to a less homogeneous surface coating, as observed in SEM analysis, and less silica present on zirconia surface (Fig. 4C and D). Application of organo-metallic precursor solutions before zirconia sintering (INF method) could theoretically improve coating retention to ceramic structure since precursors and zirconia frame sintering occurs simultaneously; hence better physical entanglement of silica layer and zirconia would be expected. However, INF method seems to be more sensitive to processing variables, as uncoated areas or areas inconsistently coated were often observed.
A μ-Raman analysis (data not shown) was also conducted in an attempt to investigate the thickness and in-depth homogeneity of silica layer. The analysis was conducted up to 10 μm deep into coating layer and failed to identify any significant differences in silica concentration. It is postulated that coating had a thickness above 10 μm, though further investigation is required to assess actual thickness of silica coat deposited on zirconia by methods proposed in this study. This information is essential since it may interfere with Obeticholic Acid of ceramic structure on abutment teeth clinically in case a very thick silica layer is formed. It is also expected that silica coating thickness may be controlled by concentration of organometallic precursors used in treatment solution as well as through the volume of solution used. Further techniques such as spin-coating or dip-coating, despite showing great efficiency in control of film thickness, would be difficult to reproduce in laboratory and clinical applications.
Previous studies proposed silica films deposition on zirconia by magnetron sputtering in a custom-made vacuum chamber using a target of ultra-pure Si [27] and [28]. Although this technique is different from methods presented in this study, the morphology of silica layer formed as well as improved adhesion to zirconia were very similar to those observed in the present study. By comparison however, the present methods seem to be simpler and more feasible for application in dental laboratories.
An additional issue concerning the technology proposed whether INF method could significantly affects structural integrity and sintering cycle of zirconia. From a structural point of view, INF method is somewhat audacious as it could alter the environmental conditions to which zirconia is subjected and also its mechanical properties. Studies evaluating dynamic and static mechanical strength should be performed in future investigations to clarify this condition. Notably, COA method appears to address the problem of yielding adhesion to zirconia ceramic clearer by using an easy and economical approach. In fact, this technique may be a feasible alternative to deposit silica onto zirconia in laboratory to improve subsequent adhesion with methacrylate-based materials. Furthermore, clinical studies are needed before broad indication of the techniques proposed in this study in order to assess their actual effectiveness, since any in vitro study has a number of limitations in predicting clinical performance of materials and techniques.
5. Conclusion
Present study introduces a novel, simple, and cost-effective method to provide adhesion of methacrylates to yttria-stabilized zirconia ceramic. The reagents used are safe, non-toxic, and reasonably inexpensive. The application technique used is also convenient as it demands same clinical and laboratory time employed in processing of oxide bioceramics. The sintering time and temperature used to process or glazing veneering ceramic could be used for SiOx condensation and networking when COA method is used, while sintering cycle of zirconia blocks could be used for INF method. Consequently, it may be concluded that experimental methods tested in this study may be useful alternative simplified low-cost approach to commercial tribochemical silicatization since they are able to provide a stable bond between resin cement and zirconia. The methods proposed could also allow bonding of other types of polymeric materials for varied applications of Y-TZP ceramics as biomaterials.