The Beneficial Clinical Effects of Teriflunomide in Experimental Autoimmune Myasthenia Gravis and the Investigation of the Possible Immunological Mechanisms.

Myasthenia gravis (MG) is an autoantibody-mediated autoimmune disease characterized by skeletal muscle weakness exacerbated with exercise. There is a need for novel drugs effective in refractory MG. We aimed to test the potential of teriflunomide, an immunomodulatory drug currently used in rheumatoid arthritis and multiple sclerosis treatment, in a murine experimental autoimmune myasthenia gravis (EAMG) model. EAMG was induced by immunizations with recombinant acetylcholine receptor (AChR). Teriflunomide treatment (10 mg/kg/day, intraperitoneal) was initiated to one group of mice (n = 21) following the third immunization and continued for 5 weeks. The disease control group (n = 19) did not receive medication. Naïve mice (n = 10) received only mock immunization. In addition to the clinical scorings, the numbers of B cells and T cells, and cytokine profiles of T cells were examined by flow cytometry. Anti-AChR-specific antibodies in the peripheral blood serum were quantified by ELISA. Teriflunomide significantly reduced clinical disease scores and the absolute numbers of CD4+ T cells and some of their cytokine-producing subgroups (IFN-γ, IL 2, IL22, IL-17A, GM-CSF) in the spleen and the lymph nodes. The thymic CD4+ T cells were also significantly reduced. Teriflunomide mostly spared CD8+ T cells' numbers and cytokine production, while reducing CD138+CD19+lambda+ plasma B cells' absolute numbers and CD138 mean fluorescent intensities, probably decreasing the number of IgG secreting more mature plasma cells. It also led to some selective changes in the measurements of anti-AChR-specific antibodies in the serum. Our results showed that teriflunomide may be beneficial in the treatment of MG in humans.

The Assessment of Different Gingival Management Materials for Immediate Implant Treatment in the Esthetic Zone: A Clinical and Biochemical Study.

PURPOSE: To observe the effect of different prosthetic materials (polymethyl methacrylate [PMMA] and flowable composite [FC]) on marginal bone loss, pink esthetic score (PES), and cytokine levels (receptor activator of nuclear factor kappa-Β ligand [RANKL] and osteoprotegerin [OPG]). MATERIALS AND METHODS: A total of 46 patients (31 women, 15 men) were treated with immediate implant therapy after tooth extraction. For standardization, only the maxillary premolar tooth of each patient was restored, and also, both of the adjacent teeth were present in the dental arch. Provisional crowns were prepared before the surgery on patient models with two different materials (24 PMMA, 22 FC). Following the surgical procedure, provisional crowns were adjusted on polyetheretherketone (PEEK) abutments as nonfunctional in centric and eccentric movements. After the surgery, patients were evaluated monthly for 3 months. At each follow-up, periapical radiography was obtained by the parallel technique, and peri-implant crevicular fluid (PICF) was collected. Pink esthetic scoring was done. MBL was calculated for the mesial and distal sides separately. Cytokine levels were analyzed from PICF. Statistical analyses (Shapiro-Wilk, Mann-Whitney U, independent-samples t test, Wilcoxon t test, paired-samples t test, and Friedman two-way analysis of variance with Bonferroni correction) were completed (α = .05). RESULTS: PES was increased significantly within groups (P < .01). However, there was no statistically significant difference between groups. According to the Mann-Whitney U test, no significant difference was found for the MBL (P > .05). When the RANKL/OPG values were evaluated within the group by using the Friedmann two-way analysis of variance test, no significant difference was found (P > .05). CONCLUSION: Similar pink esthetics, cytokine levels, and bone loss can be achieved using a protocol including immediate implants, particle grafts, soft tissue graft, PEEK abutments, and provisional restorations fabricated using PMMA and FC.

Measurement of serial serum total and acylated ghrelin levels in critically ill patients: A prospective and observational pilot study.

BACKGROUND: Ghrelin is a hormone that regulates appetite and energy metabolism. The change of serial serum total and acylated ghrelin levels during hospital stays of critical patients are unknown. In addition, the relationship of this change with the clinical results of patients in the intensive care unit (ICU) is also unknown. The aim of this study was to determine serum total and acylated ghrelin levels serially in critically ill patients. METHODS: This prospective study was performed in the ICU. Patients who were >18 years old and stayed in ICU for >48 h were included in the study. Serum total and acylated ghrelin concentrations were measured at baseline in all participants and serially on the 2nd, 5th, and 10th day after entry into the study in those who remained in the ICU. RESULTS: A total of 60 participants were included. The mean age was 56 ± 21 years. (Baseline, 2nd, 5th, and 10th day median serum total ghrelin levels were 3551 (1651-3995), 3485.20 (1379-4071), 3359 (1167-3919), and 3355 pg/ml (2207-3843), respectively. Baseline, 2nd, 5th, and 10th day acylated ghrelin levels were 47 (0-673), 50 (0-730), 73 (0-808), and 125 pg/ml (0-689), respectively. There was no significant difference between total ghrelin/acylated ghrelin levels and mortality (P > .05). ICU mortality was 30%. CONCLUSION: Ghrelin levels were decreased slightly and acylated ghrelin levels increased substantially over time in critically ill patients. There were no differences between serum total ghrelin/acylated ghrelin levels and ICU mortality .