The antimicrobial propeptide hCAP-18 plasma levels in neutropenia of various aetiologies: a prospective study.

The underlying cause of neutropenia may be difficult to determine due to similar clinical presentation in many neutropenic conditions. The neutrophil protein hCAP-18 (pro-LL-37) is a major component of neutrophil secondary granules and in this prospective study we assessed the use of hCAP-18 levels in blood plasma for differential diagnosis of neutropenic patients (n = 133) of various aetiologies. Plasma levels of hCAP-18 were determined using immunoblot and ELISA. Patients with severe congenital neutropenia (n = 23) presented with the lowest levels of plasma hCAP-18 and differential diagnostic accuracy revealed high sensitivity (100%) and specificity (98.8%) for hCAP-18 ELISA. The correlation coefficient of the hCAP-18 ELISA versus immunoblotting was (R = 0.831) and that of the peptide LL-37 ELISA versus immunoblotting was (R = 0.405) (P < 0.001). Plasma hCAP-18 levels thus displayed high diagnostic value in differential diagnosis of chronic neutropenia. Neutropenic patients with Shwachman-Diamond syndrome, Barth syndrome, Cohen syndrome, acute myeloid leukaemia and specific granule deficiency presented with reduced plasma hCAP-18 levels as well. The blood plasma level of hCAP-18 was thus low in conditions in which the neutrophil antibacterial propeptide hCAP-18 is deficient, i.e. severe congenital neutropenia and neutrophil-specific granule deficiency, and in conditions in which bone marrow myelopoiesis is negatively affected.

Pathological periodontal pockets are associated with raised diastolic blood pressure in obese adolescents.

BACKGROUND: Obesity, a well-known risk factor for developing cardiovascular disease (CVD), is associated with chronic periodontitis in adults. This cross-sectional pilot study on obese adolescents was designed to investigate whether periodontal disease in terms of pathological periodontal pockets is associated with raised blood pressure and other risk markers for CVD. METHODS: The study included 75 obese subjects between 12 to 18 years of age, mean 14.5. Subjects answered a questionnaire regarding health, oral hygiene habits and sociodemographic factors. A clinical examination included Visible Plaque Index (VPI %), Gingival inflammation (BOP %) and the occurrence of pathological pockets exceeding 4 mm (PD ≥ 4 mm). Blood serum were collected and analyzed. The systolic and diastolic blood pressures were registered. RESULTS: Adolescents with pathological periodontal pockets (PD ≥ 4 mm; n = 14) had significantly higher BOP >25% (P = 0.002), higher diastolic blood pressure (P = 0.008), higher levels of Interleukin (IL)-6 (P < 0.001), Leptin (P = 0.018), Macrophage Chemoattractant Protein-1 (MCP-1) (P = 0.049) and thyroid stimulating hormone (TSH) (P = 0.004) in blood serum compared with subjects without pathological periodontal pockets (PD ≥ 4 mm; n = 61). The bivariate linear regression analysis demonstrated that PD ≥ 4 mm (P = 0.008) and systolic blood pressure (P < 0.001) were significantly associated with the dependent variable "diastolic blood pressure". The association between PD ≥ 4 mm and diastolic blood pressure remained significant (P = 0.006) even after adjusting for potential confounders BMI-sds, age, gender, mother's country of birth, BOP >25%, IL-6, IL-8, Leptin, MCP-1, TSH and total cholesterol in the multiple regression analysis. CONCLUSION: In conclusion, this study indicates an association between pathological periodontal pockets and diastolic blood pressure in obese adolescents. The association was unaffected by other risk markers for cardiovascular events or periodontal disease. The results call for collaboration between pediatric dentists and medical physicians in preventing obesity development and its associated disorders.

Pretherapeutic plasma pro- and anti- inflammatory mediators are related to high risk of oral mucositis in pediatric patients with acute leukemia: a prospective cohort study.

OBJECTIVE: This prospective study evaluated clinical risk indicators as well as pro- and anti- inflammatory mediators at the time of malignancy diagnosis in relation to chemotherapy-related oral mucositis in pediatric population. METHODS: Patients (n = 104) under 18 years of age with primary malignancies and undergoing chemotherapy were included. Potential risk indicators were analyzed using binary logistic regression with oral mucositis as the outcome. In a subgroup (n = 35), plasma samples at the time of malignancy diagnosis were analyzed for inflammatory cytokines and an antimicrobial protein pro-LL-37 (hCAP18). RESULTS: In the multivariable model, type of malignancy diagnosis was significantly associated with oral mucositis, with highest risk of oral mucositis in patients with acute leukemia compared to those with lymphoma or solid tumors. At the time of malignancy diagnosis, plasma from patients with acute leukemia displayed higher concentrations (P<0.05) of IL-6, IL-8, IL-10, and TNF-α and lower levels of pro-LL-37 (P<0.001). CONCLUSIONS: The results imply that pretherapeutic high levels of inflammatory cytokines and low levels of pro-LL-37 in plasma might contribute to the high incidence of oral mucositis in patients with acute leukemia. These findings may add to our understanding of the predispositions to oral mucositis in children with malignancies.

Is congenital malformation a risk factor for caries development in Swedish adolescents?

OBJECTIVE: The aim of this study was to investigate whether various forms of congenital malformations are risk factors for approximal caries development in Swedish adolescents. MATERIALS AND METHODS: This longitudinal register-based cohort study included all adolescents (n = 18 142) of 13 years of age who resided in the county of Stockholm, Sweden, in 2000. The cohort was followed until individuals were 19 years of age. Dental caries (decayed, missing and filled teeth/surfaces (DMFT/S)) were collected from the Public Health Care Administration in Stockholm. Data concerning pre- and perinatal factors and parental socio-demographic determinants were collected from Swedish National Registers. RESULTS: In a logistic regression analysis, neither congenital malformation nor any sub-group of congenital malformation registered at birth were significantly associated with an enhanced risk of approximal caries increment in adolescents between 13-19 years of age. The final multivariate logistic regression model, adjusted for possible maternal and family socio-demographic confounders, showed that congenital malformation of the 'circulatory system' was significantly associated with a decreased risk of approximal caries increment, between 13-19 years of age (OR = 0.33; 95% CI = 0.12-0.88). CONCLUSIONS: Congenital malformation should not be considered as a risk factor for approximal caries development in Swedish adolescents today. Noticeably, adolescents with congenital heart diseases exhibited less risk of developing approximal caries, which was probably related to prevention programs allocated to these children in Sweden.

T-helper-related cytokines in gingival crevicular fluid from adolescents with Down syndrome.

Subjects with Down syndrome have a high prevalence of periodontal disease. The aim was to investigate the level of Th1-, Th2- and Th17-related cytokines in the gingival crevicular fluid (GCF) of subjects with Down syndrome. Subjects with Down syndrome (n = 24) and controls (n = 29) with a mean age of 16.4 years were clinically examined with respect to periodontal probing depth (PD) and gingival inflammation in terms of bleeding on probing (BOP%). The controls were matched to subjects with Down syndrome regarding age and gingival inflammation (BOP%). All subjects answered a questionnaire regarding oral hygiene, medical history and socioeconomic background. GCF was collected and the concentration of the cytokines, IFN-γ, TNF-α, IL-1ß, IL-4, IL-6, IL-10, IL-12 and IL-17 were determined using Bio-Plex cytokine multiplex assays. The volume of GCF (microliters) was significantly higher in subjects with Down syndrome (P < 0.001) compared with controls. The mean concentrations (picogrammes per millilitre) of IL-1ß (P < 0.001), IL-4 (P = 0.002), IL-6 (P = 0.005), IL-10 (P = 0.001), IL-12 (P = 0.003), IFN-γ (P = 0.002), and TNF-α (P = 0.002) in GCF, respectively, were significantly higher in subjects with Down syndrome compared with controls. The regression line of the relationship between IFN-γ and IL-4 in GCF differed significantly (P = 0.006) in subjects with Down syndrome compared to controls. Subjects with Down syndrome demonstrated higher concentration of Th1-, Th2- and Th17-related cytokines with an altered relationship between Th1 cytokine, IFN-γ and Th2 cytokine, IL-4, in volume GCF compared to controls.

Microbiota in the oral subgingival biofilm is associated with obesity in adolescence.

To test the hypothesis whether microbiota in oral biofilm is linked with obesity in adolescents we designed this cross-sectional study. Obese adolescents (n = 29) with a mean age of 14.7 years and normal weight subjects (n = 58) matched by age and gender were examined with respect to visible plaque index (VPI%) and gingival inflammation (bleeding on probing (BOP%)). Stimulated saliva was collected. They answered a questionnaire concerning medical history, medication, oral hygiene habits, smoking habits, and sociodemographic background. Microbiological samples taken from the gingival crevice was analyzed by checkerboard DNA-DNA hybridization technique. The sum of bacterial cells in subgingival biofilm was significantly associated with obesity (P < 0.001). The link between sum of bacterial cells and obesity was not confounded by any of the studied variables (chronic disease, medication, VPI%, BOP%, flow rate of whole saliva, or meal frequency). Totally 23 bacterial species were present in approximately threefold higher amounts, on average, in obese subjects compared with normal weight controls. Of the Proteobacteria phylum, Campylobacter rectus and Neisseria mucosa were present in sixfold higher amounts among obese subjects. The association between obesity and sum of bacterial cells in oral subgingival biofilm indicates a possible link between oral microbiota and obesity in adolescents.

Mutations in the ELANE gene are associated with development of periodontitis in patients with severe congenital neutropenia.

BACKGROUND: Patients with severe congenital neutropenia (SCN) often develop periodontitis despite standard medical and dental care. In light of previous findings that mutations in the neutrophil elastase gene, ELANE, are associated with more severe neutropenic phenotypes, we hypothesized an association between the genotype of SCN and development of periodontitis. METHODS: Fourteen Swedish patients with SCN or cyclic neutropenia harboring different genetic backgrounds were recruited for periodontal examination. Peripheral blood, gingival crevicular fluid (GCF), and subgingival bacterial samples were collected. The levels of cytokines and antibacterial peptides were determined in GCF and plasma by multiplex immunoassay and immunoblotting, respectively. Subgingival bacterial samples were analyzed using 16S rDNA pyrosequencing. RESULTS: ELANE mutations correlated with more severe periodontal status than the HAX1 or unknown mutations in patients with SCN. The subjects with mutant ELANE had higher levels of IL-1ß in GCF. Using principal coordinate analysis of the subgingival microbiota, patients with ELANE mutations and reference subjects with periodontitis tended to cluster differently from patients with HAX1 or unknown mutations and non-periodontitis reference subjects. CONCLUSION: This study demonstrates an association between ELANE mutations in SCN and the development of periodontitis with skewed subgingival microbiota, indicating a potential role of ELANE mutations in the pathogenesis of periodontitis.

Expression of prostaglandin E synthases in periodontitis immunolocalization and cellular regulation.

The inflammatory mediator prostaglandin E(2) (PGE(2)) is implicated in the pathogenesis of chronic inflammatory diseases including periodontitis; it is synthesized by cyclooxygenases (COX) and the prostaglandin E synthases mPGES-1, mPGES-2, and cPGES. The distribution of PGES in gingival tissue of patients with periodontitis and the contribution of these enzymes to inflammation-induced PGE(2) synthesis in different cell types was investigated. In gingival biopsies, positive staining for PGES was observed in fibroblasts and endothelial, smooth muscle, epithelial, and immune cells. To further explore the contribution of PGES to inflammation-induced PGE(2) production, in vitro cell culture experiments were performed using fibroblasts and endothelial, smooth muscle, and mast cells. All cell types expressed PGES and COX-2, resulting in basal levels of PGE(2) synthesis. In response to tumor necrosis factor (TNF-α), IL-1ß, and cocultured lymphocytes, however, mPGES-1 and COX-2 protein expression increased in fibroblasts and smooth muscle cells, accompanied by increased PGE(2), whereas mPGES-2 and cPGES were unaffected. In endothelial cells, TNF-α increased PGE(2) production only via COX-2 expression, whereas in mast cells the cytokines did not affect PGE(2) enzyme expression or PGE(2) production. Furthermore, PGE(2) production was diminished in gingival fibroblasts derived from mPGES-1 knockout mice, compared with wild-type fibroblasts. These results suggest that fibroblasts and smooth muscle cells are important sources of mPGES-1, which may contribute to increased PGE(2) production in the inflammatory condition periodontitis.

Association between obesity and periodontal risk indicators in adolescents.

OBJECTIVE: In a cross-sectional study design we test the hypothesis of whether obesity in adolescence is associated with periodontal risk indicators or disease. STUDY DESIGN: Obese adolescents (n=52) and normal weight subjects (n=52) with a mean age of 14.5 years were clinically examined with respect to dental plaque, gingival inflammation, periodontal pockets and incipient alveolar bone loss. The subjects answered a questionnaire concerning medical conditions, oral hygiene habits, smoking habits and sociodemographic background. Body mass index (BMI) was calculated and adjusted for age and gender (BMI-SDS). Samples of gingival crevicular fluid (GCF) were analyzed for the levels of adiponectin, plasminogen activator inhibitor-1 (PAI-1), interleukin-1ß (IL-ß), interleukin-8 (IL-8) and tumor necrosis factor α (TNF-α). RESULTS: Obese subjects exhibited more gingival inflammation (P<0.001) and more pathological periodontal pockets (>4 mm) (P<0.001) but not incipient alveolar bone loss compared with the normal weight subjects. Higher levels of IL-1ß (P<0.001) and IL-8 (P=0.002) were measured in GCF from obese subjects compared with the controls. In a multivariate logistic regression analysis, adjusted BMI-SDS (P=0.03; Odds Ratio [OR]=1.87) was significantly associated with the occurrence of pathological periodontal pockets. CONCLUSION: The study demonstrates an association between obesity and periodontal risk indicators in adolescents that in the long term may lead to oral morbidity. This result further strengthens obesity's negative effect on teenagers' periodontal health and highlights the importance of a close collaboration between dentists and pediatricians in the prevention and treatment of obesity.

Migration background: a risk factor for caries development during adolescence.

The influence of child and parental migration background on the risk of approximal caries increment in Swedish adolescents was investigated. This retrospective longitudinal register-based cohort study included all 13-yr-old adolescents (n = 18,142) who were resident in the County of Stockholm, Sweden, in 2000, and followed them up to 19 yr of age. At follow-up, 15,538 subjects were examined. Caries data [decayed, missing, and filled teeth/surfaces (DMFT/S)], were collected from a dental database. Socio-demographic determinants were collected from Swedish National Registers. After adjustments for socio-demographic confounders, logistic regression analysis revealed that adolescents with foreign-born parents, irrespective of whether the child was born in Sweden or abroad, exhibited a significantly elevated risk for approximal caries increment (DMFSa > 0), and developed, on average, 0.53 and 1.14 more approximal caries lesions, respectively, compared with their counterparts with Swedish-born parents. Furthermore, adolescents born in eastern Europe exhibited an increased risk for approximal caries increment (DMFSa > 0) and developed, on average, 1.06 more approximal caries lesions compared with Swedish-born adolescents. In conclusion, parental migration background must be considered as a risk factor for caries development during adolescence, irrespective of whether or not the adolescent was born in Sweden.

Signal pathways JNK and NF-kappaB, identified by global gene expression profiling, are involved in regulation of TNFalpha-induced mPGES-1 and COX-2 expression in gingival fibroblasts.

BACKGROUND: Prostaglandin E2 (PGE2) is involved in several chronic inflammatory diseases including periodontitis, which causes loss of the gingival tissue and alveolar bone supporting the teeth. We have previously shown that tumor necrosis factor alpha (TNFalpha) induces PGE2 synthesis in gingival fibroblasts. In this study we aimed to investigate the global gene expression profile of TNFalpha-stimulated primary human gingival fibroblasts, focusing on signal pathways related to the PGE2-synthesizing enzymes prostaglandin E synthases (PGES), as well as the upstream enzyme cyclooxygenase-2 (COX-2) and PGE2 production. RESULTS: Microarray and western blot analyses showed that the mRNA and protein expression of the inflammatory induced microsomal prostaglandin E synthase-1 (mPGES-1) was up-regulated by the cytokine TNFalpha, accompanied by enhanced expression of COX-2 and increased production of PGE2. In contrast, the expression of the isoenzymes microsomal prostaglandin E synthase-2 (mPGES-2) and cytosolic prostaglandin E synthase (cPGES) was unaffected by TNFalpha treatment. Using oligonucleotide microarray analysis in a time-course factorial design including time points 1, 3 and 6 h, differentially expressed genes in response to TNFalpha treatment were identified. Enrichment analysis of microarray data indicated two positively regulated signal transduction pathways: c-Jun N-terminal kinase (JNK) and Nuclear Factor-kappaB (NF-kappaB). To evaluate their involvement in the regulation of mPGES-1 and COX-2 expression, we used specific inhibitors as well as phosphorylation analysis. Phosphorylation analysis of JNK (T183/Y185) and NF-kappaB p65 (S536) showed increased phosphorylation in response to TNFalpha treatment, which was decreased by specific inhibitors of JNK (SP600125) and NF-kappaB (Bay 11-7082, Ro 106-9920). Inhibitors of JNK and NF-kappaB also decreased the TNFalpha-stimulated up-regulation of mPGES-1 and COX-2 as well as PGE2 production. CONCLUSION: In the global gene expression profile, the enrichment analysis of microarray data identified the two signal transduction pathways JNK and NF-kappaB as positively regulated by the cytokine TNFalpha. Inhibition of these TNFalpha-activated signal pathways reduced the expression of mPGES-1 and COX-2 as well as their end product PGE2 in gingival fibroblasts. The involvement of the signal pathways JNK and NF-kappaB in the regulation of PGE2 induced by TNFalpha may suggest these two pathways as possible attractive targets in the chronic inflammatory disease periodontitis.

Association between obesity, flow rate of whole saliva, and dental caries in adolescents.

In a cross-sectional study design, we test the hypothesis whether childhood obesity is associated with reduced flow rate of stimulated whole saliva and dental caries. Obese adolescents (n = 65) with a mean age of 14.5 years and normal weight subjects (n = 65) with a mean age of 14.2 years were clinically examined with respect to dental caries, visible plaque accumulation (visible plaque index (VPI%)), gingival inflammation in terms of bleeding on probing (BOP%) as well as answered a questionnaire concerning medical history, medication, oral hygiene habits, smoking habits, and sociodemographic background. The flow rate of stimulated whole saliva (ml/min) was determined. BMI was calculated and adjusted for age and gender (BMI-sds). The obese subjects exhibited higher number of decayed surfaces (DS), 0.7 vs. 0.1 (P = 0.008) and lower flow rate of stimulated whole saliva 1.2 vs. 2.0 ml/min (P < 0.001). Of obese patients, 17 subjects had VPI% >25 and 21 had BOP% >25, both compared to only 5 subjects of the normal weight with P values of 0.005 and <0.001, respectively. In a multivariate logistic regression model BMI-sds was significantly associated with the flow rate of stimulated whole saliva less than the median value 1.5 ml/min (P < 0.001; odds ratio (OR) 1.36) as well as with DS (DS >0) (P = 0.002; OR 1.31) and the associations were not found to be confounded by any of the studied variables. The results indicate that childhood obesity is associated with reduced flow rate of stimulated whole saliva and dental caries and further strengthens obesity's negative effect on children's oral health.

Maternal overweight and smoking: prenatal risk factors for caries development in offspring during the teenage period.

This study aimed to investigate pre- and perinatal determinants as risk factors for caries development in offspring. In this longitudinal register-based cohort study, we included all children (n = 18,142), of 13 years of age who resided in the county of Stockholm, Sweden, in 2000. The cohort was followed until individuals were 19 years of age. In total, 15,538 subjects were examined. Dental caries (decayed, missing and filled teeth/surfaces), were collected from the Public Health Care Administration in Stockholm. Data concerning pre- and perinatal factors, as well as parental socio-demographic determinants, were collected from the Swedish Medical Birth Register and Swedish National Registers at Statistics Sweden. Mean approximal caries increment (DMFSa) was 1.34 +/- 2.74. The results showed that the prenatal factors, "maternal smoking" and "maternal overweight" exhibited an increased risk of approximal caries increment, (OR 1.33; 95% CI = 1.22-1.44) and (OR 1.21; 95% CI = 1.07-1.37), respectively. Concerning maternal overweight, the excess risk enhanced in relation to the magnitude of the caries increment and maternal smoking was significant across the various DMFSa outcome cut-off levels. In conclusion, this study demonstrates that the prenatal factors, maternal overweight, as well as smoking, are risk factors for approximal caries development in offspring during the teenage period.

Risk factors and risk indicators in relation to incipient alveolar bone loss in Swedish 19-year-olds.

OBJECTIVE: To investigate incipient alveolar bone loss and subgingival calculus on a subject-based level in Swedish 19-year-olds, with special reference to risk factors and risk indicators. MATERIAL AND METHODS: Subjects (n=686) with different socio-economic profiles enrolled at seven public dental clinics in suburban Stockholm answered a questionnaire on general health, tobacco habits, oral hygiene habits, and their parents' socio-economic background. The clinical and radiographic examination included registration of plaque, bleeding on probing (GBI), supra- and subgingival calculus, caries, and restorations. Incipient alveolar bone loss was recorded when the distance from the cemento-enamel junction to the alveolar crest was > or =2.0 mm. RESULTS: The prevalence of incipient alveolar bone loss was 5.1%; multivariate analysis disclosed the associated variables to be "subgingival calculus" (odds ratio (OR) 4.2) and "proximal restoration > or =1" (OR 2.1). The cumulative probability of exhibiting incipient alveolar bone loss was 19.6%. The prevalence of subgingival calculus was 14.3% and subgingival calculus was associated with "GBI > 25%" (OR 6.0), "supragingival calculus" (OR 4.6), and "father born abroad" (OR 2.8). The cumulative probability of exhibiting subgingival calculus was estimated to be 65.3%. CONCLUSIONS: Adolescents with subgingival calculus as well as proximal restorations are at higher relative risk of exhibiting incipient alveolar bone loss than are those without subgingival calculus. In contrast to incipient alveolar bone loss, immigrant background was significantly associated with subgingival calculus among Swedish adolescents.

Regulation of prostaglandin E synthases: effects of siRNA-mediated inhibition of microsomal prostaglandin E synthase-1.

Prostaglandin E2 (PGE2) is a key mediator involved in several inflammatory conditions. In this study, we investigated the expression and regulation of the terminal PGE2 synthesizing enzyme prostaglandin E synthases (mPGES-1, mPGES-2 and cPGES) in gingival fibroblasts stimulated with pro-inflammatory cytokines. We used siRNA knockdown of mPGES-1 to elucidate the impact of mPGES-1 inhibition on mPGES-2 and cPGES expression, as well as on PGE2 production. The cytokines TNFalpha and IL-1beta increased protein expression and activity of mPGES-1, accompanied by increased COX-2 expression and PGE2 production. The isoenzymes mPGES-2 and cPGES, constitutively expressed at mRNA and protein levels, were unaffected by the pro-inflammatory cytokines. We show for the first time that treatment with mPGES-1 siRNA down-regulated the cytokine-induced mPGES-1 protein expression and activity. Interestingly, mPGES-1 siRNA did not affect the cytokine-stimulated PGE2 production, whereas PGF(2alpha) levels were enhanced. Neither mPGES-2 nor cPGES expression was affected by siRNA silencing of mPGES-1. Dexamethasone and MK-886 both inhibited the cytokine-induced mPGES-1 expression while mPGES-2 and cPGES expression remained unaffected. In conclusion, mPGES-1 siRNA down-regulates mPGES-1 expression, and neither mPGES-2 nor cPGES substituted for mPGES-1 in a knockdown setting in gingival fibroblasts. Moreover, mPGES-1 siRNA did not affect PGE2 levels, whereas PGF(2alpha) increased, suggesting a compensatory pathway of PGE2 synthesis when mPGES-1 is knocked down.

Risk factors and risk indicators associated with high caries experience in Swedish 19-year-olds.

OBJECTIVE: To study the risk factors and risk indicators associated with high caries experience (DMFS >or= 10) in 19-year-olds. MATERIAL AND METHODS: The subjects (n=800) lived in seven suburbs of Stockholm and answered a structured questionnaire about their parents' education, occupation, and country of birth, as well as their dietary habits, oral hygiene habits, and attitudes to dental care. Dental caries was assessed by clinical and radiographic examination using the decayed, missing, filled teeth (DMFT), and surfaces (DMFS) indices. Dental plaque (VPI%) and gingival bleeding (GBI%) indices were recorded. RESULTS: A total of 696 subjects (364 M, 332 F) participated in the study. The mean DMFT and DMFS were 3.9 and 5.1, respectively. In 81% of subjects, the DMFT was >or= 1 and 15% had DMFS >or= 10. In the multivariate analysis, the variables significantly associated with high caries experience were: dental fear (p<0.001, odds ratio (OR) 2.8), GBI >or= 15% (p=0.003, OR 2.1), mother born abroad (p=0.007, OR 2.0) and irregular toothbrushing at night (p=0.008, OR 1.9). When all significant variables in the multivariate analysis were present, the cumulative probability of DMFS >or= 10 was 52%. CONCLUSIONS: Dental fear, gingival inflammation, a foreign-born mother, and irregular toothbrushing at night are variables that are strongly associated with high caries experience in 19-year olds. The study indicates that foreign-born parents, oral hygiene habits, and behavioral factors still have a strong impact on dental health in late adolescence.

Cell interactions between human gingival fibroblasts and monocytes stimulate the production of matrix metalloproteinase-1 in gingival fibroblasts.

BACKGROUND: Matrix metalloproteinase-1 (MMP-1) plays an important role in inflammatory diseases including periodontitis, which is characterized by tissue destruction and dense infiltration of mononuclear cells. OBJECTIVES: The aim of this study was to investigate the effect of cell interactions between human gingival fibroblasts and human monocytes on the production of MMP-1 in a coculture model. METHODS: The fibroblasts were cultured in either cell-to-cell contact with monocytes or in separated cocultures using a microporous membrane to prevent cell-to-cell contact. The mRNA expression of MMP-1 was analyzed using reverse transcription-polymerase chain reaction (RT-PCR) and the protein levels of MMP-1 in the cell medium were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Coculturing gingival fibroblasts with monocytes in cell-to-cell contact increased the mRNA expression of MMP-1 in both fibroblasts and monocytes. The protein levels of MMP-1 increased in the culture media of the cocultures and correlated to the number of fibroblasts as well as to the number of monocytes. When fibroblasts were cultured with monocytes in separated cocultures, the mRNA expression and protein level of MMP-1 increased in the fibroblasts. In addition, treatment of fibroblasts with conditioned medium from monocytes also stimulated the production of MMP-1 in the fibroblasts. Moreover, the levels of the MMP-1 inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), increased in cocultures with cell-to-cell contact, but not in fibroblasts of separated cocultures. The glucocorticoid dexamethasone and the tetracycline doxycycline reduced the enhanced level of MMP-1 in the cocultures with cell-to-cell contact. CONCLUSION: The current study demonstrates that monocytes stimulate the production of MMP-1 in gingival fibroblasts by cell interactions, which may contribute to the maintenance of MMP-mediated tissue destruction in periodontitis.

Cell expression of MMP-1 and TIMP-1 in co-cultures of human gingival fibroblasts and monocytes: the involvement of ICAM-1.

Matrix metalloproteinase-1 (MMP-1) plays an important role in the degradation of collagen in inflammatory diseases. The aim of this study was to investigate the cellular expression of MMP-1 and its inhibitor, tissue inhibitor of metalloproteinase-1 (TIMP-1), in gingival fibroblasts co-cultured with monocytes and the possible mediating role of intercellular adhesion molecule-1 (ICAM-1). In co-cultures, the expression of MMP-1 and TIMP-1 increased in fibroblasts, but not in monocytes, although the number of MMP-1+ and TIMP-1+ adhered monocytes increased. Moreover, ICAM-1 expression in both fibroblasts and adhered monocytes increased. In the presence of an anti-ICAM-1 antibody, the expression of MMP-1 in fibroblasts decreased whereas the number of TIMP-1+ adhered monocytes increased. The p38 MAPK inhibitor SB203580 reduced MMP-1 expression in fibroblasts, as well as ICAM-1 expression in both fibroblasts and adhered monocytes. The results suggest that co-culture with monocytes enhances cellular expression of MMP-1 and TIMP-1 in gingival fibroblasts, and that the increased MMP-1 expression, in contrast to TIMP-1, is partly mediated by the adhesion molecule ICAM-1 and the p38 MAPK signal pathway.

Induction of microsomal prostaglandin E synthase-1 in human gingival fibroblasts.

It is well established that prostaglandin E2 (PGE2) plays an important role in inflammatory diseases including periodontitis. Previously we have reported that the inflammatory mediators interleukin-1beta, (IL-1beta) and tumor necrosis factor alpha (TNFalpha) stimulate PGE2 synthesis by inducing mRNA expression of cyclooxygenase-2 (COX-2) in human gingival fibroblasts. In present study the involvement of microsomal prostaglandin E synthase-1 (mPGES-1) in relation to PGE2 production was investigated. The results showed that IL-1beta as well as TNFalpha induced mPGES-1 mRNA and protein expression accompanied by enhanced PGE2 production in gingival fibroblasts. The anti-inflammatory steroid dexamethasone (DEX) inhibited mPGES-1 mRNA and protein expression as well as PGE2 production induced by IL-1beta or TNFalpha. The COX-2 specific inhibitor, celecoxib, in contrast to the nonspecific COX inhibitor, indomethacin, markedly reduced mPGES-1 expression induced by IL-1beta. The results demonstrate that mPGES-1 regulates PGE2 production in gingival fibroblasts stimulated by inflammatory mediators IL-1beta and TNFa. This novel pathway may be a potential target for treatment strategies of periodontal disease.

Correlation between TNFalpha in gingival crevicular fluid and body mass index in obese subjects.

The aim of this study was to investigate the relationship between body mass index (BMI kg/m2), the inflammatory mediator tumor necrosis factor alpha (TNFalpha), and interleukin-8 (-8) in gingival crevicular fluid (GCF) from 32 obese subjects aged between 13 and 24 years. Gingival inflammation (GBI %), pathological pocket depths, and alveolar bone loss diagnosed on radiographs were recorded. The GCF was collected from six sites per subject using periopaper, and the volume was determined using Peritron 8000. The levels of TNFalpha and IL-8 were determined using ELISA kits. Within the whole group, there was no significant relationship between BMI and the variables age, GBI %, number of periodontal pockets, smoking, and the levels of TNFalpha or IL-8. In subjects with BMI > or =40, however, there was a statistically significant correlation (r= 0.74, P< 0.01) between the level of TNFalpha in GCF and BMI. The correlation coefficient between BMI and TNFalpha in subjects with BMI > or =40 differed significantly (P< 0.05) compared to that between subjects with BMI <40. The level of TNFalpha in GCF was positively correlated (P< 0.05) with BMI in subjects with no periodontal pathological pocket. No significant correlation was found between the level of IL-8 and BMI. The results indicate that BMI positively correlates with TNFalpha in GCF in the group of young subjects with BMI > or =40 as well as in the subjects with no pathological periodontal pocket (> or =4 mm) and that TNFalpha in GCF may be affected by the obese condition through a systemic effect.