Impact of Non-Surgical Periodontal Treatment on the Concentration and Level of MRP-8/14 (Calprotectin) as an Inflammatory Biomarker in Women with Periodontitis and Rheumatoid Arthritis: A Quasi-Experimental Study.

The aim of this study was to evaluate the impact of non-surgical periodontal treatment (NS-PT) on periodontal parameters and inflammatory biomarkers in the concentration and level of calprotectin (CLP) in women with periodontitis and rheumatoid arthritis (RA). In this quasi-experimental study, we evaluated 30 women (mean age: 52.0 ± 5.8 years) with periodontitis and RA who had been diagnosed and treated for RA for more than 3 years and whose activity markers remained at similar values without significant reduction over three consecutive months. Patients underwent NS-PT, which included plaque control, scaling, and root planing. Serum and saliva samples, periodontal indices, RA activity markers, Disease Activity Score-28 (DAS28), the erythrocyte sedimentation rate (ESR), and the C-reactive protein (CRP) and CLP contents were measured at the beginning of the study and 6 and 12 weeks after NS-PT. Parametric and nonparametric tests were used in the analysis. The mean age was 52.0 ± 5.8 years. Compared to the baseline results, all periodontal indices were significantly reduced 6 and 12 weeks after NS-PT (p < 0.001). DAS28 was also significantly reduced after 12 weeks (p < 0.0001). Similarly, the serum CLP concentration decreased 6 and 12 weeks after NS-PT (p < 0.0001). Of the patients, 100% presented lower levels of CRP and ESR (p < 0.0001). Overall, NS-PT reduced inflammation and disease activity, highlighting the importance of oral health in the control and treatment of systemic diseases such as RA and confirming that NS-PT effectively reduces periodontitis activity and plays a key role in modulating RA activity. Therefore, NS-PT should be considered as an adjunct treatment for RA.

Nucleus-Independent Chemical Shift (NICS) as a Criterion for the Design of New Antifungal Benzofuranones.

The assertion made by Wu et al. that aromaticity may have considerable implications for molecular design motivated us to use nucleus-independent chemical shifts (NICS) as an aromaticity criterion to evaluate the antifungal activity of two series of indol-4-ones. A linear regression analysis of NICS and antifungal activity showed that both tested variables were significantly related (p < 0.05); when aromaticity increased, the antifungal activity decreased for series I and increased for series II. To verify the validity of the obtained equations, a new set of 44 benzofuran-4-ones was designed by replacing the nitrogen atom of the five-membered ring with oxygen in indol-4-ones. The NICS(0) and NICS(1) of benzofuran-4-ones were calculated and used to predict their biological activities using the previous equations. A set of 10 benzofuran-4-ones was synthesized and tested in eight human pathogenic fungi, showing the validity of the equations. The minimum inhibitory concentration (MIC) in yeasts was 31.25 µg·mL-1 for Candida glabrata, Candida krusei and Candida guilliermondii with compounds 15-32, 15-15 and 15-1. The MIC for filamentous fungi was 1.95 µg·mL-1 for Aspergillus niger for compounds 15-1, 15-33 and 15-34. The results obtained support the use of NICS in the molecular design of compounds with antifungal activity.

Population pharmacokinetics of mycophenolic acid in adult kidney transplant patients under prednisone and tacrolimus regimen.

Mycophenolate mofetil (MMF) is typically used in combination with prednisone and tacrolimus to avoid graft rejection in kidney transplant patients. The aim of this study was to develop and validate a population pharmacokinetic model of mycophenolic acid (MPA) in kidney transplant patients to investigate the influence of clinical and genetic covariates and to propose a dosage regimen based on the final model. Adult kidney transplant patients (>18 years old) receiving combination of MMF, prednisone and tacrolimus regimen were included. The population pharmacokinetic model was built using a two-compartment model and First Order Conditional Estimation method with Interaction (FOCEI though NONMEM v.7.4.). A total of 343 MPA concentrations at steady state from 77 kidney transplant patients were included in the analysis. MPA CL/F, V1/F, Q/F, V2/F, and Ka were 12.4 L/h, 45.6 L, 29.9 L/h, 658 L, and 1.67 h-1, respectively. It was found that CL/F increases with serum creatinine and uric acid levels and V1/F is modified by blood urea nitrogen and the UGT1A9 genotype. In the final model the interindividual variabilities associated to CL/F and V1/F were 56.5% and 105.8%, respectively. The residual variability was 41.8%. Evaluation by bootstrapping showed that the final model was stable. The predictive performance was evaluated by goodness-of-fit plots and visual predictive check. Dosage regimens for MMF were proposed based on the final model and would be appropriate for a prospective evaluation. In conclusion, it was built a population pharmacokinetic model for MPA in kidney transplant patients, which include clinical and genetic covariates.

Dosing recommendations based on population pharmacokinetics of tacrolimus in Mexican adult patients with kidney transplant.

The aim of this study was to perform a population pharmacokinetic analysis of tacrolimus in Mexican adult kidney transplant patients to analyse the influence of clinical and genetic covariates to propose a dosage regimen. Kidney transplant patients (>18 years old) receiving oral tacrolimus treatment were included in the current study. The population pharmacokinetic model was built using a one-compartment model and the First Order Conditional Estimation method with Interaction (FOCEI via NONMEM v.7.3.). A total of 600 tacrolimus trough blood concentrations from 52 kidney transplant patients were analysed. Tacrolimus clearances were 26, 18.8 and 12.3 L/h, for patients with genetic polymorphisms CYP3A5*1*1, *1*3 and *3*3, respectively. The influence of haematocrit was inversely related to tacrolimus clearance, following an allometric power function. Total volume of distribution was 604 L. Interindividual variability associated with tacrolimus clearance and distribution volume for the final model was 33 and 63%, respectively, with a residual error of 2.5 ng/mL. Relative bioavailability was calculated between generic formulations A (0.53) and B (1) of tacrolimus. Internal validation was performed through bootstrap analysis to evaluate the stability of the final model; external validation was performed in a new group of patients (n = 13) to estimate residual errors on basic (57.8%) and final (34.8%) models. Finally, stochastic simulations were performed to propose a dosage regimen based on haematocrit, CYP3A5 genotype and generic formulation of tacrolimus. A stable and predictive population pharmacokinetic model of tacrolimus was developed for Mexican adult kidney transplant patients; additionally, the proposed dosage regimen of tacrolimus should be prospectively validated.