The Role of Interleukin 6 in Periodontitis and Its Complications.

Interleukin 6 (IL-6) is a pleomorphic pro-inflammatory cytokine that is strongly associated with local as well as systemic inflammatory processes. Its role in physiological and pathogenic processes throughout the human body has been the subject of numerous studies in recent years. Measurements of the IL-6 levels in gingival crevicular fluid (GFC), as well as in serum, can be important diagnostic and prognostic factors in periodontal diseases (PD) and in assessing their impact on a range of related inflammatory diseases. This narrative review explores the significant role of IL-6 in patients with periodontitis and its association with other widespread inflammatory pathologies.

Human macrophage immunometabolism regulator (MACIR) in patients with periodontitis.

OBJECTIVE: Periodontitis is a local inflammatory reaction caused by bacterial infection in which immune cells, including macrophages, are involved. Recent studies have shown that an important regulator of macrophage function is the human macrophage immunometabolism regulator (MACIR). This gene has been shown to play a key role in modulating the immune response by affecting the activity of fibroblasts and macrophages. In this study, we investigated the expression of MACIR in the gingival tissues of patients with periodontal disease, as well as the effect of IL-1ß and TNF-α on the expression of MACIR gene and protein in human gingival fibroblasts. METHODS: MACIR mRNA expression in gingival tissue samples was determined using Real-time PCR. Expression of MACIR protein was determined using immunofluorescent staining and western blotting. RESULTS: The MACIR mRNA expression in gingival tissue samples in patients with periodontitis was statistically significantly lower than in gingival tissue samples from healthy controls (p = 0.009). The stimulation of human gingival fibroblasts with IL-1ß and TNF-α resulted in a statistically significant decrease of MACIR gene mRNA expression. In western blotting and immunofluorescent analysis, we confirmed that the stimulation of the primary culture of human gingival fibroblasts by both IL-1ß and TNF-α decreases the expression of MACIR protein. CONCLUSION: The results of the study suggest that MACIR is an important regulator of the inflammatory process in patients with periodontitis. Decreased expression of the MACIR gene may activate macrophages to secrete mediators that increase inflammation and cause periodontal tissue destruction.

Expression of Interleukin 17A and 17B in Gingival Tissue in Patients with Periodontitis.

Periodontitis (PD) is a chronic inflammatory disease that is initiated by oral microorganisms. The pathogens induce the production of cytokines, such as interleukin (IL)-17, which enhances the inflammatory response and progression of the disease. The aim of this study was to examine the expression and localization in gingival tissue of IL-17A and IL-17B in patients with periodontitis. This study included 14 patients with periodontal disease and 14 healthy subjects without periodontal disease as a control group. There were no statistically significant differences in the expression of IL-17A mRNA between patients with periodontitis and control subjects. The expression of IL-17B mRNA was statistically significantly lower in patients with periodontitis in comparison with healthy subjects (p < 0.048). The expression of IL-17A correlated significantly with the approximal plaque index. The IL-17B expression in gingival tissue correlated with the clinical attachment level. This correlation reached borderline statistical significance (p = 0.06). In immunohistochemical analysis, we have shown the highest expression of IL-17 protein in inflamed connective tissue, epithelium, and granulation tissue from gingival biopsy specimens from patients with periodontitis. In biopsy specimens from healthy individuals, no IL-17 was found in the epithelium, while an expression of IL-17 was found in the connective tissue. The results of our study confirm the involvement of IL-17 in the pathogenesis of periodontitis. Our results suggest that an increase in IL-17 protein expression in the gingival tissue of patients with periodontitis occurs at the post-translational stage.

Clinical Factors and the Outcome of Treatment with Methotrexate in Rheumatoid Arthritis: Role of Rheumatoid Factor, Erosive Disease and High Level of Erythrocyte Sedimentation Rate.

To identify the clinical factors predicting the outcome of treatment with methotrexate in rheumatoid arthritis, we examined 312 patients (253 females, 59 males) with rheumatoid arthritis diagnosed according to the criteria of the American College of Rheumatology. All patients included in this analysis began treatment with a regimen of oral MTX 7.5 mg weekly, with the dosage increasing to 15 mg weekly after 4 weeks, in combination with folic acid (1 mg daily). Good responders were defined as patients who had a DAS28 of ≤2.4 at 6 months (patients with remission of disease symptoms). Poor responders were defined as patients who had a DAS28 of >2.4. In this study, we analyzed the association between clinical parameters such as sex of patients, age of patients, age at disease onset, disease duration, rheumatoid factor, anti-CCP antibodies, ESR values, presence of joints erosions, presence of extra-articular manifestations and the response to MTX in RA patients. Multivariate logistic regression analysis showed four independent factors significantly associated with good response to MTX treatment: older age at disease onset, low ESR, no erosive disease and negative RF. The results of our study suggest that a younger age at disease onset, the presence of RF, erosive disease, as well as a high level of ESR are associated with worse response to MTX therapy.

IL-18 Gene rs187238 and rs1946518 Polymorphisms and Expression in Gingival Tissue in Patients with Periodontitis.

Periodontitis is a chronic disease with disturbed balance between the immune and inflammatory response of the host to bacteria. Many studies have shown that proinflammatory cytokines play a significant role in the pathogenesis of periodontal disease. In this study, we examined the association between the IL-18 gene rs187238 and rs1946518 polymorphisms and periodontitis in non-smoking and smoking patients. This study enrolled 200 patients with periodontitis (130 non-smokers and 70 smokers) and 156 control subjects (124 non-smokers and 32 smokers). There were no statistically significant differences in the distribution of the rs187238 and rs1946518 IL-18 genotypes and alleles between patients with periodontitis and control subjects, between smoking patients with periodontitis and smoking control subjects, and between non-smoking patients with periodontitis and non-smoking control subjects. There were no statistically significant differences in clinical parameters in relation to the IL18 rs187238 genotypes. In patients with the IL18 rs1946518 GG genotype, we observed increased values of bleeding on probing (BoP) and periodontal probing depth (PPD), compared to subjects with the TT genotype. In patients with periodontitis, we observed statistically significant decreased expression of the IL-18 gene in comparison with healthy subjects (0.231 ± 0.163 vs. 0.663 ± 0.197, p = 0.0008). In addition, the IL-18 gene expression in gingival tissue in patients with periodontitis correlated positively with the number of remaining teeth. The results of our study suggest that the IL-18 rs187238 and rs1946518 polymorphisms are not significant risk indicators of periodontitis in our population. However, in patients with the IL18 rs1946518 GG genotype, we observed increased values of BoP and PPD, compared to subjects with the TT genotype. In addition, in gingival tissue of patients with periodontitis, we have detected decreased expression of IL-18. The gingival expression of IL-18 in patients with periodontitis correlated positively with number of remaining teeth. The above results suggest that IL-18, in addition to its pro-inflammatory effects in periodontal disease, may also exhibit protective properties.

IL-17F Gene rs763780 and IL-17A rs2275913 Polymorphisms in Patients with Periodontitis.

Background: Periodontitis (PD) is a chronic inflammatory disease that can eventually lead to tooth loss. Genetic and environmental factors such as smoking are involved in the pathogenesis of PD. The development of PD is potentiated by various pathogens that induce an immune response leading to the production of cytokines, such as interleukin (IL)-17. The synthesis of IL-17 is influenced genetically. The polymorphisms in IL-17 gene may affect the synthesis of IL-17. The aim of this study was to examine the association between the IL-17F rs763780 and IL-17A rs2275913 polymorphisms and PD in non-smoking and smoking patients to check if these polymorphisms could be a risk factor for PD. Methods: The study enrolled 200 patients with PD (130 non-smokers and 70 smokers) and 160 control subjects (126 non-smokers and 34 smokers). Periodontitis was diagnosed on the basis of 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. All samples were genotyped using allelic discrimination assays with TaqMan® probes on a Real-Time PCR Detection System. Results: There were no statistically significant differences in the distribution of the IL-17F rs763780 and IL-17A rs2275913 genotypes and alleles between patients with PD and control subjects, between smoking patients with PD and smoking control subjects, and between non-smoking patients with PD and non-smoking control subjects. Conclusions: The results of this study suggest a lack of statistically significant associations between IL-17F rs763780 and IL-17A rs2275913 polymorphisms and PD in Polish population.

Cytokines and Their Genetic Polymorphisms Related to Periodontal Disease.

Periodontal disease (PD) is a chronic inflammatory disease caused by the accumulation of bacterial plaque biofilm on the teeth and the host immune responses. PD pathogenesis is complex and includes genetic, environmental, and autoimmune factors. Numerous studies have suggested that the connection of genetic and environmental factors induces the disease process leading to a response by both T cells and B cells and the increased synthesis of pro-inflammatory mediators such as cytokines. Many studies have shown that pro-inflammatory cytokines play a significant role in the pathogenesis of PD. The studies have also indicated that single nucleotide polymorphisms (SNPs) in cytokine genes may be associated with risk and severity of PD. In this narrative review, we discuss the role of selected cytokines and their gene polymorphisms in the pathogenesis of periodontal disease.

Lack of Association Between the VEGFA Gene Rs699947 Polymorphism and Periodontal Disease.

PURPOSE: Periodontal disease is a chronic inflammatory disease characterised by the infiltration of inflammatory cells as well as activation of pathological angiogenesis in gingival tissues. Vascular endothelial growth factor (VEGF) plays a statistically significant role in the regulation of angiogenesis and induction of an inflammatory response in periodontal tissues. MATERIALS AND METHODS: We examined the association between the VEGFA gene rs699947 polymorphism and periodontal disease. This study enrolled 200 patients with periodontal disease (130 non-smokers and 70 smokers) and 160 control subjects (126 non-smokers and 34 smokers). RESULTS: There were no statistically significant differences in the distribution of VEGFA rs699947 genotypes and alleles between patients with periodontal disease and control subjects, also in the case when the analysis was performed in subgroups stratified according to smoking status. CONCLUSION: The results of this study suggest there is no association between the VEGFA gene rs699947 polymorphism and periodontal disease.

New therapies for the treatment of heart failure: a summary of recent accomplishments.

Despite continuous efforts to prevent cardiovascular diseases (CVDs), heart failure prevails as the number one cause of death in developed countries. To properly treat CVDs, scientists had to take a closer look at the factors that contribute to their pathogenesis and either modernize current pharmaceuticals or develop brand new treatments. Enhancement of current drugs, such as tolvaptan and omecamtiv mecarbil, sheds new light on already-known therapies. Tolvaptan, a vasopressin antagonist, could be adopted in heart failure therapy as it reduces pre- and afterload by decreasing systolic blood pressure and blood volume. Omecamtiv mecarbil, which is a myosin binding peptide, could aid cardiac contractility. The next generation vasodilators, serelaxin and ularitide, are based on naturally occurring peptides and they reduce peripheral vascular resistance and increase the cardiac index. In combination with their anti-inflammatory properties, they could turn out to be extremely potent drugs for heart failure treatment. Cardiotrophin has exceeded many researchers' expectations, as evidence suggests that it could cause sarcomere hypertrophy without excessive proliferation of connective tissue. Rapid progress in gene therapy has caused it to finally be considered as one of the viable options for the treatment of CVDs. This novel therapeutic approach could restore stable heart function either by restoring depleted membrane proteins or by balancing the intracellular calcium concentration. Although it has been set back by problems concerning its long-term effects, it is still highly likely to succeed.

IL-1ß rs1143634 and rs16944 polymorphisms in patients with periodontal disease.

BACKGROUND: Periodontal disease (PD) is a chronic inflammatory condition caused by pathogenic microflora in a biofilm, often leading to tooth loss. The inflammatory response of periodontal tissues to infection is influenced by both environmental and genetic factors. The interleukin (IL)-1 family of proinflammatory cytokines plays a role in the tissue destruction associated with PD due to their proinflammatory and bone-resorptive properties. In addition, recent studies have indicated that polymorphisms in the genes encoding IL-1 might be associated with greater PD severity. In this study, we examined the association between IL-1ß rs1143634 and rs16944 polymorphisms and PD in non-smoking and smoking patients. MATERIALS AND METHODS: This study included 200 patients with PD (130 non-smokers and 70 smokers) and 156 control subjects (124 non-smokers and 32 smokers). Periodontal evaluation included approximal plaque index, modified sulcus bleeding index, probing pocket depth and clinical attachment loss. Genotyping was utilized for all samples by using allelic discrimination assays with TaqMan® probes on a 7500Fast Real-Time PCR Detection System. RESULTS: There were no statistically significant differences in the distribution of rs1143634 and rs16944 genotypes and alleles between patients with PD and control subjects, between smoking patients with PD and smoking controls, or between non-smoking patients with PD and non-smoking controls. CONCLUSIONS: The results of this study suggest there is no association between IL-1ß rs1143634 and rs16944 polymorphisms and PD.

Analysis of Base Monomer Elution from 3 Flowable Bulk-Fill Composite Resins Using High Performance Liquid Chromatography (HPLC).

BACKGROUND The aim of this study was to evaluate the elution of BisGMA, UDMA, TEGDMA, and HEMA monomers from flowable bulk fill composite resins with different resin matrix compositions, polymerized in 4-mm-thick layers, into 3 elution media. MATERIAL AND METHODS Three bulk-fill (SDR® (SDR), X-tra base (XB) and BEAUTIFIL-Bulk Flowable (BF)) resin-composites were tested. Cylindrical samples were immersed in 100% ethanol, 75% ethanol, and distilled water. The concentrations of the monomers were measured using the HLPC method (Agilent Technologies 1200 Series) after 1 and 24 h, as well as after 3, 7, 14, and 21 days. RESULTS After polymerization of the tested resins, there was elution of the BisGMA, UDMA, TEGDMA, and HEMA monomers from the SDR and BF composites, but none of the tested monomers could be detected eluting from XB. The highest penetrations of the polymerized SDR and BF composites were observed in the 100% ethanol solution. This extraction medium eluted the highest amounts of free monomers. Some eluted monomers were not described in the composites Material Safety Data Sheets. CONCLUSIONS The elution of the residual monomers depended on the resin composition and the materials filler/resin matrix ratio. In composite materials, toxicity assessment should be carried out, and should consider both the material composition as given by the manufacturer, and also the residual monomers that elute from the polymerized material. The elution concentration and time of monomers from composites depended on the solvent used. The highest penetrations of the polymerized SDR and BF composites were observed in the 100% ethanol solution, and this extraction medium eluted the highest amounts of free monomers. The 75% ethanol was a more aggressive medium than water in terms of monomer elution from bulk fill composites.

Genetic factors in pathogenesis of diabetes mellitus after kidney transplantation.

Posttransplant diabetes mellitus (PTDM) is one of the major metabolic complications after transplantation of solid organs including the kidney. This type of diabetes mellitus affects allograft survival, cardiovascular complications and overall patient survival. The modifiable risk factors that contribute to PTDM include obesity, some viral infections (eg, hepatitis C virus, cytomegalovirus) and especially immunosuppressive drugs including corticosteroids, tacrolimus, cyclosporine and sirolimus. Currently, predisposing genetic factors have been considered important in PTDM development. The commonly evaluated genetic determinants include genes encoding transcription factors, cytokines, chemokines, adipokines, ionic channels, glucose transporters, cytochrome P450 enzymes and other enzymes metabolizing drugs, drug transporters. Unfortunately, the results of studies are inconclusive and differ between populations. There is a need for large genome-wide association study to identify the genetic risk factors associated with PTDM development.

The influence of KIR gene presence/absence polymorphisms on the development of periodontal disease in smokers and non-smokers.

INTRODUCTION: Periodontal diseases are highly prevalent inflammatory, multifactorial diseases. Smoking is one of the most important environmental risk factors for the development and severity of periodontal disease. Killer cell immunoglobulin-like receptors (KIRs) are members of the immunoglobulin (Ig) superfamily and play an essential role in the regulation of NK cell activity, allowing natural killer (NK) cells to sense and respond to human leukocyte antigen (HLA) class I. The aim of this study was to evaluate the influence of KIR gene presence/absence polymorphisms on the development of periodontal disease in smokers and non-smokers. MATERIAL AND METHODS: This study enrolled 400 Caucasian subjects (age range 25-69 years) from the West Pomeranian region of Poland. The subjects were categorized into four subgroups (smoking and non-smoking patients with periodontal disease; smoking and non-smoking subjects without periodontal disease - control subjects). RESULTS: The differences of KIR gene frequencies between non-smoking patients and non-smoking control subjects as well as smoking patients and control subjects were not statistically significant. In multivariate regression analysis advanced age of patients and smoking were independent factors associated with increased frequency of periodontal disease. CONCLUSIONS: The results of this study suggest that the main factor associated with increased risk of periodontal disease is smoking, whereas KIR presence/absence polymorphism is not a significant factor involved in the pathogenesis of periodontal disease.

Are KIR genes associated with clinical parameters in the course of periodontitis?

INTRODUCTION: Periodontitis is a common chronic inflammatory disease. It seems that natural killer (NK) cells play a role in the pathogenesis of periodontitis. KIRs are a family of inhibitory or activating receptors expressed on the surfaces of NK cells and some subpopulations of T lymphocytes. The aim of this study was to evaluate the impact of KIR genes on the pocket depth (PD) and clinical attachment loss (CAL) parameter values as markers of disease clinical course. MATERIALS AND METHODS: The patients in the study were submitted to anamnesis and to clinical and periodontal examination. The subjects (400) were categorized into two groups: periodontitis (250 including 100 with moderate and 140 with severe periodontitis) and controls (150). Both groups were divided into two subgroups: KIR gene positive (presence of KIR gene in the genome) and KIR gene negative (lack of the KIR gene in the genome). RESULTS: The mean value for CAL was more than 5 mm, and the mean value for PD was more than 4 mm in the periodontitis group. The ANOVA test performed for the control group showed that neither PD nor CAL parameters differed between particular KIR-positive and KIR-negative healthy individuals. Similar results were obtained for all subgroups of chronic periodontitis patients and periodontitis patients (moderate as well as severe): no association between KIR genes and PD or CAL parameters was found. DISCUSSIONS: The activated immune system is important in pathogenesis of periodontal disease. On the other hand, tissue damage as a response to infection could be due to activation mediated by KIR. In our study no association between either KIR genes presence or absence and PD and CAL parameters was found. Nevertheless, the impact of KIR genes on the clinical course of periodontal disease requires further investigations.

[Interaction between fluorine and zinc after long-term oral administration into the digestive system of rats]. / Wzajemne oddzialywanie fluoru i cynku po wielokrotnym podawaniu droga przewodu pokarmowego u szczurów.

Drug interactions are the side effect of administration of two or more drugs or a drug-food combination. Although some drug interactions are intentional and beneficial to the patient, the majority are unintentional and associated with a potentially harmful effect. The aim of this study was to search for interactions in rats between fluoride and zinc administered orally for 12 weeks and to elucidate any potential toxicological and therapeutic consequences. 60 male Wistar rats were divided into six groups of ten rats each and exposed to: 1. controls (distilled water); 2. sodium fluoride (NaF); 3. low-dose zinc (Zn); 4. high-dose zinc; 5. NaF + low-dose Zn; 6. NaF + high-dose Zn. At the end of the experiment the content of F- and Zn+ in serum, urine, incisors, femur and mandible was measured and densitometry of femoral bones was performed. Serum alkaline phosphatase, alanine and aspartate aminotransferase activities, as well as bilirubin and creatinine concentrations were determined to confirm non-toxicity of fluoride dose. Animals receiving NaF only demonstrated higher content of fluorine in serum, urine bones and teeth. Zinc concentrations in serum, urine, bones and teeth were elevated in rats receiving zinc with or without NaF. Fluorine accumulation in bones and teeth was reduced by Zn, but in general the effect lacked statistical significance. Zinc slightly reduced the concentrations of fluorine in serum and urine. Sodium fluoride slightly reduced the concentration of zinc in serum and urine. Bone mineral content (BMC) was significantly increased by NaF and was not further increased by co-administration of zinc. No changes in serum alkaline phosphatase, alanine and aspartate aminotransferase activities, bilirubin and creatinine concentrations were detected. In conclusion, simultaneous administration of fluorine and zinc may be beneficial for prevention and treatment of pathologic conditions in bones and teeth and is not accompanied by an increase in fluorine levels which could be responsible for toxicological symptoms.