Common variants of genes encoding TLR4 and TLR4 pathway members TIRAP and IRAK1 are effective on MCP1, IL6, IL1β, and TNFα levels in type 2 diabetes and insulin resistance

Objective and design

Type 2 diabetes is a pandemic disease characterized by hyperglycemia, ineffective insulin use, and insulin resistance and affecting 1 in 11 people worldwide. Inflammation-related insulin resistance is thought to play an important role in the etiology of the disease. TLR4 is the central receptor of the natural immune system and has an important role as a trigger of the inflammatory response. The IRAK1 and TIRAP are members of the TLR4 pathway and involved in the TLR4-mediated inflammatory response. Genetic variants in the TLR4 gene or in the IRAK1 and TIRAP genes may have an important role in the development of insulin resistance and type 2 diabetes by disrupting the inflammatory response. In this direction, we aimed to investigate the relationship among TLR4 and IRAK1, TIRAP gene variants, and type 2 diabetes and insulin resistance, and investigate how these variants affect inflammatory factors (TNF-α, IL-6, MCP-1, and IL-1β).

Subjects and methods

In our study, a total of seven variations on the genes of TLR4 (rs4986790, rs4986791), IRAK1 (rs1059703, rs3027898, rs7061789), and TIRAP (rs8177374, rs8177400) were genotyped by the MassARRAY^® Iplex GOLD SNP genotyping in 100 type 2 diabetic patients and 100 non-diabetic individual. The TLR4 rs4986790 and rs4986791 variation was confirmed by PCR–RFLP method also. The serum IL1-β, IL6, MCP-1, and TNF-α levels were measured using enzyme-linked immunosorbent assay kits.

Results and conclusion

As a result of our study, no correlation was found among TLR4, IRAK1, and TIRAP gene variants and the risk of type 2 diabetes and insulin resistance. However, TNF-α, IL-6, MCP-1, and IL-1β levels were also associated with diabetes and insulin resistance (p?>?0.05). Although the gene variants were not significant in type 2 diabetes and insulin resistance groups, IRAK1, TLR4, and TIRAP gene variants were found to be associated with TNF-α, IL-6, MCP-1, and IL-1β levels.

     

Lost in translation? A critical look at the role that animal models of obsessive compulsive disorder play in current drug discovery strategies

Introduction: Obsessive-compulsive disorder (OCD) is a severe neuropsychiatric illness estimated to affect between 1–3% of the population. In today’s literature, there are a number well-validated and convincing animal models of OCD described.

Areas covered: Herein, the authors look at the role that animal models of OCD (including transgenic models, deer mouse stereotypy, quinpirole sensitization, post-training signal attenuation, and mouse marble burying) have played in determining the current directions of OCD drug discovery. Specifically, the article reviews new OCD drug therapies currently under investigation including drugs that target glutamate, dopamine, serotonin, and endocannabinoid systems. The authors review the published results of these clinical trials, and critically examine the contribution of animal models to the development of these novel therapies.

Expert opinion: Nitric oxide inhibitors, oxycarbazepine, and modulators of serotonin and metabotropic glutamate receptors should be further explored in animal models as well as in clinical trials. Pregabalin, topiramate, lamotrigine, sarcosine, minocycline, L-carnosine, celecoxib, and ondansetron, which have shown promise in clinical trials, should be explored in animal models with the goal of understanding the neurobiology of their effects. A multidisciplinary, interactive approach to OCD drug discovery, where animal models generate neurobiological hypotheses that can be tested in the clinic, and vice versa, should be cultivated.     

Effects of various finishing procedures on the staining of provisional restorative materials

STATEMENT OF PROBLEM: The color stability of tooth-colored restorative materials for provisional restorations is of primary importance when provisional prostheses are worn long term. However, the effect of different polishing methods on the color difference of provisional restorative (PR) materials has not been completely clarified. PURPOSE: The purpose of this study was to investigate the effect of different polishing methods on color stability of 2- and 3-component autopolymerized bis-acrylic composites, a light polymerized composite, and a methyl methacrylate-based PR material upon exposure to a staining agent. Material and methods Sixty cylindrical specimens (15 x 2 mm) were prepared for each of bis-acryl composites (Protemp II and Luxatemp), a light-polymerized composite (Revotek LC), and a methyl methacrylate-based (TemDent) PR material by using a brass mold. The specimens were divided into 6 groups (n=10), and different polishing procedures were used, including pumice (P), diamond polishing paste (Dpp), polishing discs (Pd), and combinations of these. Unpolished specimens served as the control. The specimens were stored for 48 hours at 37 degrees C in a coffee solution. The color of all specimens was measured with a colorimeter (Minolta CR-300) before and after exposure, and color changes (DeltaE) were calculated. The data were analyzed with a 2-way analysis of variance, and mean values were compared by the Tukey Honestly Significant Difference test (alpha=.05). RESULTS: The provisional materials, surface polishing procedures, and interaction were significant (P <.05). In the light-polymerized composite group, the lowest color difference (DeltaE) was observed in Group P-Dpp (4.9) and Group P (5.3), which were not significantly different from each other. In the autopolymerized bis-acryl composites and the methyl methacrylate-based provisional materials, the lowest color difference (DeltaE) was observed in Group P-Dpp. The largest color difference for the light-polymerized and autopolymerized composites was observed in Group Pd-Dpp and Group Pd, which were not significantly different from each other. In the methyl methacrylate-based material group, the largest color difference was observed in Group Pd. When comparing the 4 different PR materials, the methyl methacrylate-based material group demonstrated statistically significantly less color change than the other provisional material tested. CONCLUSION: The methyl methacrylate-based PR material (TemDent) was found to be more color stable than the autopolymerized (Protemp II and Luxatemp) and light-polymerized (Revotek LC) composites tested. The use of diamond polishing paste after polishing with pumice significantly decreased the staining of methyl metacrylate and bis-acryl composites tested. The highest color-change values were obtained in the groups polished with polishing discs, which were found to be significantly different compared to values obtained with other polishing techniques.     

Periodontal health in various ethnic groups in Israel

The periodontal status of approximately 5,000 subjects belonging to nine ethnic groups of Oriental origin, aged four years and above and living in villages in Israel, was investigated. The severity of periodontal involvement of a group was found to be similar whether expressed as gingivitis in childhood or as destructive periodontal disease in adolescence and adult life. Gingivitis reached its peak at the age of 10 to 11 years and then tended to level off or even decline. The periodontal index (PI) and gingival recession rate (GRR) both formed straight line graphs between the ages of 17 and 55+. The incidence and prevalence of periodontal disease were almost uniformly higher in males than in females. In the populations investigated in the present study, it appears unwarranted to attribute this difference to differences in attitude to oral health and hygiene between the sexes. The possibility that habitual chewing of the leaves of Catha edulis is a causative factor in the exceptionally high rates of periodontal disease in Yemenite males is discussed. The periodontal health of the best groups was inferior to that of white Americans, and of the same order as that of American Negroes and the inhabitants of Lebanon and Chile. The most severe degree of involvement was comparable to findings in South-East Asia, and occurred in people who had immigrated from India.     

A prospective 5-year multicenter study of the Cresco implantology concept

PURPOSE: The purpose of this study was to investigate the clinical and radiographic outcome of a prospective 5-year longitudinal multicenter test of a simplified implantology concept comprising an abutment-free implant system (Cresco) and a new method for fabrication of passively fitting superstructures, the Cresco Ti Precision method. MATERIALS AND METHODS: The tests were carried out at three different centers. Sixty partially or completely edentulous patients were restored by fixed implant-supported superstructures fabricated according to the Cresco Ti Precision method. In all, 215 Cresco implants were placed for the support of the superstructures. For various reasons, eight patients (13%) could not be followed through the 5 years. The radiographic measurements were recorded from radiographs exposed perpendicular to the implants. RESULTS: The initial implant failure rate (during the healing phase) was 2%, and the survival rate after loading was 98%. The mean peri-implant bone loss was 0.29 mm (SD 0.57). Of the measured sites, 71% showed a crestal bone loss of less than 0.5 mm. Very few mechanical complications were observed. This was attributed to the passively fitting superstructures. CONCLUSION: The results from the present multicenter test demonstrated that the abutment-free Cresco implantology concept is a reliable alternative method for implant-supported fixed prosthetic rehabilitation of edentulous and partially edentulous jaws.     

Effects of different drinks on stainability of resin composite provisional restorative materials

STATEMENT OF PROBLEM: The ability of tooth-colored restorative materials for provisional restorations to resist stains is important when interim prostheses are worn for a long period. Discoloration of provisional restorative materials may result in patient dissatisfaction and additional time and expense for replacement. However, the effect of different staining agents on the color difference of resin composite restorative materials has not been completely clarified. PURPOSE: The purpose of this study was to evaluate the stainability of auto- and light-polymerized composite provisional restorative materials, reinforced microfill, and microhybrid resin composite restorative materials upon exposure to different staining agents. MATERIAL AND METHODS: Forty-five cylindrical specimens (15 x 2 mm) were prepared for each of an autopolymerized bis-acryl composite provisional restorative material (Protemp II), a light-polymerized composite provisional restorative material (Revotek LC), a reinforced microfill (Micronew), and a microhybrid composite (Filtek Z250, Herculite XRV) restorative material, using a brass mold. The specimens were wet-ground with 1000-grit silicon carbide abrasive paper for 10 seconds. The 5 restorative material specimens were divided into 9 groups (n = 5) and stored for 24 hours at 37 degrees C in different types of solutions: water, coffee, coffee with sugar, tea, tea with sugar, coffee with artificial creamer and sugar, cola, red wine, or sour cherry juice. Color of all specimens was measured before and after exposure with a colorimeter using CIE L * a * b * relative, and color changes (DeltaE * ) were then calculated. The data were analyzed with a 2-way analysis of variance (ANOVA), and mean values were compared by the Tukey HSD test (alpha = .05). RESULTS: The interaction of provisional restorative materials and staining agents was statistically significant ( P = .0001). For the 5 restorative materials tested, the lowest DeltaE * values were observed in the water, cola, and sour cherry juice groups. The highest color difference for all restorative materials was observed in the red wine groups. For microhybrid composite materials and light-polymerized composite provisional material, when tea and coffee groups with and without sugar were compared, both groups with sugar demonstrated a higher color difference than without sugar. When comparing the 5 different restorative materials, the reinforced microfill material group (Micronew) demonstrated significantly less color change than the other materials tested. The highest color difference in this study was observed for specimens in the light-polymerized composite provisional material group (Revotek LC). CONCLUSION: The reinforced microfill restorative material tested was found significantly more color stable than the autopolymerized bis-acryl, light-polymerized composite provisional restorative materials, and microhybrid composites tested. The largest color difference was observed in the light-polymerized composite provisional material. The presence of sugar in coffee and tea increased the color difference compared to coffee or tea without sugar for light-polymerized composite provisional material and microhybrid composites.