Association between serum and oral matrix metalloproteinase-8 levels and periodontal health status.

BACKGROUND AND OBJECTIVE: Matrix metalloproteinase-8 (MMP-8) is involved in a wide range of pathologies including periodontitis and cardiovascular diseases (CVD). The association between periodontitis and CVD has been repeatedly recognized. The aim of the study was to analyze to what extent circulating active MMP-8 (aMMP-8) is associated with periodontal disease status and oral fluid aMMP-8 levels in otherwise healthy subjects. MATERIAL AND METHODS: In a cross-sectional study, aMMP-8 was measured in serum of 59 volunteers, comprising 19 periodontally healthy subjects, 20 patients with gingivitis as well as 20 with periodontitis. All study subjects were characterized regarding aMMP-8 concentrations in different oral fluids as well as clinically and microbiologically with respect to periodontal disease. aMMP-8 levels in gingival crevicular fluid were measured using the enzyme-linked immunosorbent assay. Saliva enzyme levels as well as circulating aMMP-8 were determined by a time-resolved immunofluorometric assay. Both methods utilized the same monoclonal antibodies. Correlation and regression analyses were performed to study the potential association between serum aMMP-8 and oral parameters. RESULTS: Oral aMMP-8 levels were significantly higher in patients with periodontitis compared to periodontally healthy or gingivitis subjects. Highest serum aMMP-8 concentration was also found in the periodontitis group. The serum levels correlated significantly with oral aMMP-8 as well as with clinical parameters in a dose-dependent manner. These results were confirmed in a multivariate regression analysis. After adjusting for potential confounders, saliva aMMP-8 concentrations as well as periodontitis severity were significant predictors of serum aMMP-8. CONCLUSION: The associations between circulating aMMP-8 and oral aMMP-8 as well as periodontal findings in a dose-dependent manner may contribute to linking periodontal disease with increased CVDsusceptibility.

Evaluation of a novel point-of-care test for active matrix metalloproteinase-8: agreement between qualitative and quantitative measurements and relation to periodontal inflammation.

BACKGROUND AND OBJECTIVES: Severe periodontitis affects about 10% of the world population. In addition, associations between periodontitis and systemic diseases exist. Therefore, the diagnosis should be made quickly and at an early stage. Matrix metalloproteinase-8 (MMP-8) is the most prominent collagenase found in inflamed periodontal tissues. Its active form (aMMP-8) is increasingly used as a diagnostic biomarker. Aim of the present study is to evaluate the diagnostic accuracy of a novel aMMP-8 point-of-care (POC) test in comparison to the standard laboratory test to diagnose the disease rapidly and reliably. MATERIAL AND METHODS: In a prospective, mono-center, double-blinded, case-control study, participants with healthy gums (n = 35), gingivitis (n = 60) and periodontitis (n = 35) were investigated before and after therapy. Beside clinical variables for plaque and inflammation, aMMP-8 concentrations were determined in oral rinsing specimens by the enzyme-linked immunosorbent assay (ELISA) and by POC. Positive and negative percent agreements with their exact one-sided lower 95% confidence limits were calculated. RESULTS: Of 130 participants, 111 finished the study. Overall, positive percent agreements were 75.8% (57.7-88.9) before treatment and 73.7% (56.9-86.6) after treatment. Negative percent agreements were 92.8% (85.7-97.0) before and 93.3% (85.1-97.8) after treatment. Positive test results (POC and ELISA) ranged from 5.7% to 8.6% in healthy patients, 25.0-29.8% in patients with gingivitis and 40.0-48.1% in patients with periodontitis. Patients who had positive aMMP-8 test results (POC) showed higher scores for plaque and inflammation. CONCLUSIONS: The novel POC test to detect aMMP-8 has proved to agree strongly with the standard method, ELISA. The test can be recommended to screen patients at risk for periodontitis in dental offices, at the general practitioner and at specialists for associated diseases.

Numerical Investigation of Active Flow Control Around a Generic Truck A-Pillar.

Large Eddy Simulations (LES) are conducted to study the actuated flow field around a bluff body. The model is a simplified section of a truck. The aim of the work is to model the separation of the flow acting at the front rounded corners, the so called A-pillars, and to minimize the separation of the flow by means of Zero Net Mass Flux synthetic jets. LES data show the interaction of the flow main structures, the separation mechanism and the effects of the actuation on the flow field. The flow is post processed using modal and frequency decompositions. Relevant results in terms of drag reduction were observed for the actuated flow. The principle flow mechanisms are discussed and an optimal actuation frequency, in terms of induced fluctuations and drag reduction, is identified.

COX-2 is associated with periodontitis in Europeans.

COX-2 plays an important role in periodontitis by mediating inflammatory reactions in periodontal tissues, and the COX-2 polymorphisms rs20417 and rs689466 have been reported to be associated with periodontitis in populations of Taiwanese and Chinese ethnicity. To test whether these variants were associated with periodontitis in populations of European ethnicity, we genotyped the single-nucleotide polymorphisms (SNPs) rs689466 and rs6681231, the latter a haplotype tagging SNP (htSNP) for rs20417 (r2>0.95), in our large-analysis population of individuals with aggressive (n = 532) and chronic periodontitis (n = 1052), and 2873 healthy control individuals. The rare G allele of htSNP rs6681231 was associated with aggressive periodontitis prior to and after adjustment for the covariates smoking, diabetes, and gender, with an odds ratio of 1.57 (95% confidence interval 1.18-2.08; p = 0.002). The validation of the association of rs20417 by the htSNP rs6681231 provides evidence for a general genetic risk of COX-2 variants in the pathogenesis of periodontitis.

A 3' UTR transition within DEFB1 is associated with chronic and aggressive periodontitis.

Periodontal diseases are complex inflammatory diseases and affect up to 20% of the worldwide population. An unbalanced reaction of the immune system toward microbial pathogens is considered as the key factor in the development of periodontitis. Defensins have a strong antimicrobial function and are important contributors of the immune system toward maintaining health. Here, we present the first systematic association study of DEFB1. Using a haplotype-tagging single nucleotide polymorphism (SNP) approach, including described promoter SNPs of DEFB1, we investigated the associations of the selected variants in a large population (N=1337 cases and 2887 ethnically matched controls). The 3' untranslated region SNP, rs1047031, showed the most significant association signal for homozygous carriers of the rare A allele (P=0.002) with an increased genetic risk of 1.3 (95% confidence interval: 1.11-1.57). The association was consistent with the specific periodontitis forms: chronic periodontitis (odds ratio=2.2 (95% confidence interval: 1.16-4.35), P=0.02), and aggressive periodontitis (odds ratio=1.3 (95% confidence interval 1.04-1.68), P=0.02). Sequencing of regulatory and exonic regions of DEFB1 identified no other associated variant, pointing toward rs1047031 as likely being the causative variant. Prediction of microRNA targets identified a potential microRNA-binding site at the position of rs1047031.

Effect of N-chlorotaurine mouth rinses on plaque regrowth and plaque vitality.

The purpose of this 4-day plaque regrowth study was to assess the effect of N-chlorotaurine (NCT) mouth rinses on plaque inhibition and plaque vitality. Eighty volunteers participated in this investigator-blind, randomized, clinical controlled study in parallel groups. No oral hygiene was permitted except rinsing with a 2% or 3% NCT mouth rinse, a positive or a negative control. Primary parameters were the plaque index (Silness and Löe, Acta Odontol Scand, 22:121-135, 1964) and plaque vitality (Netuschil et al., J Clin Periodontol, 16:484-488, 1989) after the final rinse. In addition, another plaque index (Turesky et al., J Periodontol, 41:41-43, 1970), plaque area, and bleeding on probing were recorded. All parameters were taken at baseline and day 5. U test was applied on a 5% error level. No differences in plaque inhibition were found between the two NCT formulations and the negative control. However, a statistically significant reduction of plaque vitality compared to the negative and positive control was observed. Discoloration of the tongue and unpleasant taste were recorded in participants in the NCT groups. NCT mouth rinses did not inhibit plaque regrowth, but they did reduce the vitality of plaque bacteria. Methods of prolonging the substantivity of the NCT mouth rinses should be investigated to enhance the antibacterial properties of these formulations.

Cathepsin C gene variants in aggressive periodontitis.

Cathepsin C (CTSC) mutations are known to cause Papillon-Lefèvre syndrome. The aim of this study was to examine the association of CTSC genotype with susceptibility to non-syndromic aggressive periodontitis. The CTSC gene was analyzed in 110 persons with generalized aggressive periodontitis in comparison with 78 control individuals, after identifying different variants in a cohort of 100 persons. Five out of 19 discovered variants were included in this association study, representing 5 single-nucleotide polymorphism groups in tight linkage disequilibrium. The relevance of genotypes on enzyme function was examined. The carrier frequency of the missense variant p.I453V was significantly increased in persons with disease compared with healthy control individuals (17.3% vs. 6.4%, p < 0.05). CTSC activity in leukocytes from individuals harboring this variant was significantly reduced (119.8 Delta OD/min*10(5) cells, 95% confidence interval 17.4-174.9, p = 0.018). No influence of promoter variants was found on mRNA expression. The results support the hypothesis that CTSC gene variants contribute to increased susceptibility in generalized aggressive periodontitis.

[Urolithiasis in children--rational diagnosis, therapy, and metaphylaxis]. / Urolithiasis bei Kindern--rationelle Diagnostik, Therapie und Metaphylaxe.

With a proportion of 1-5%, children constitute only a small number of all patients with urolithiasis. Nevertheless, pediatric stone disease is an important health care problem because of the high recurrence rate and the threat of progredient renal function impairment with consecutive loss of quality of life. Modern therapies, especially extracorporeal shock wave lithotripsy (ESWL), ureteroscopy (URS), and percutaneous nephrolithotomy (PCNL), have caused a revolution in the operative treatment spectrum. Open surgery is required for stone removal only rarely, such as for the simultaneous repair of urinary tract anomalies. The minimally invasive modalities of modern stone therapy - mainly ESWL as the treatment of first choice - have led to widespread disregard of stone metaphylaxis. The important principle that says an urinary stone is just a symptom and not the cause of the disease is often forgotten. So it must be noted that despite the high standard of care in Germany, not all problems regarding urinary stone disease are being resolved, particularly in childhood. This article presents the current knowledge of the most important aspects of stone therapy and the methods of treatment in children.

Periodontal therapy in siblings with Papillon-Lefèvre syndrome and tinea capitis: a report of two cases.

OBJECTIVE: Report of clinical and microbiological periodontal findings before and 6 months after treatment of two siblings with Papillon-Lefèvre syndrome (PLS) and tinea capitis. METHODS: Two brothers, RG 3 years and NG 5 years of age, were referred for treatment due to premature mobility of their deciduous teeth. Probing depths (PPD), attachment levels (PAL-V), and furcation involvements were examined clinically. Panoramic radiographs were taken. Subgingival plaque samples within the deepest pocket of each tooth were taken and analysed by real-time polymerase chain reaction (PCR) for Actinobacillus actinomycetemcomitans (AA), Porphyromonas gingivalis, Tannerella forsythensis, Treponema denticola, Fusobacterium nucleatum, and Prevotella intermedia. One-stage full-mouth scaling and extraction of hopeless teeth were performed under general anaesthesia, followed by systemic amoxicillin and metronidazole for 7 days. Clinical and microbiological analyses were performed 6 months after treatment. RESULTS: Before treatment, both siblings had exhibited PPD of up to 13 mm, Class III furcation defects at four teeth, and marginal suppuration. AA was detected in both patients and at all teeth at levels ranging from 3.0 x 10(2) to 5.1 x 10(6). Both patients exhibited palmar and plantar hyperkeratosis. Seven teeth were extracted from RG, and nine from NG. Six months after treatment, PPD had been reduced to

CARD15 gene variants in aggressive periodontitis.

OBJECTIVE: The CARD15 gene encodes a protein that acts as an intracellular receptor of bacterial products, thus playing an important role in the innate immune response. Recently, CARD15 gene variants have been identified as a cause of increased susceptibility to Crohn's disease. The present study aimed to examine a potential association of CARD15 gene variants with aggressive periodontitis susceptibility. MATERIAL AND METHODS: The three main known CARD15 gene variants (p.R702W, p.G908R, and p.L1007fsX1008) were analysed by direct sequencing of exon 4, 8, and 11 of the gene in a total of 86 generalized aggressive periodontitis patients in comparison with 67 healthy controls. RESULTS: The mutant allele frequencies of the CARD15 variants were low in the generalized aggressive periodontitis group as well as in the control group and not significantly different (R702W: 3.5% versus 5.2%; G908R: 1.7% versus 1.5%; L1007fsX1008: 5.2% versus 4.5%). Two rare variants (A755V and R791Q), previously described only in patients with other inflammatory diseases, were observed in three patients having aggressive periodontitis but not in controls. CONCLUSIONS: Unlike in Crohn's disease, our results did not show an association between the three main CARD15 mutations and aggressive periodontitis. The role of rare variants remains unclear.

Periodontal status and preterm low birth weight: a case control study.

BACKGROUND: Previous studies have suggested that periodontal disease may be an important risk factor for preterm low birth weight. However, the link between periodontal health status of pregnant women and preterm low birth weight is contentious, as recent studies found no association between periodontitis and pregnancy outcome. OBJECTIVE: The aim of this study was to investigate this potential link in a German Caucasian population. METHODS: Fifty-nine pregnant women with a high risk for a preterm low birth weight infant (suffering from preterm contractions, cases, group 1) as well as 42 control women with no preterm contractions during pregnancy and having an infant appropriate for date and weight (>or= 37 weeks gestation, >or= 2500 g, group 2) were examined. Clinical periodontal status was recorded on a full mouth basis. Subgingival plaque samples were taken and periodontal pathogens were identified by polymerase chain reaction. Additionally, interleukin-1 beta level in gingival crevicular fluid was analysed. RESULTS: The mean percentage of sites showing moderate to advanced attachment loss (>or=3 mm) was low in all study groups (group 1: 9.9 +/- 11.2%; group 2:10.6 +/- 14.1%, respectively). No significant differences between the groups in any aspects of the studied periodontitis parameters could be detected. Using a logistic regression model controlling for known preterm low birth weight risk factors, no periodontitis-associated factors increased risk for preterm contractions or preterm low birth weight. The odds ratio (OR) was 1.19 for preterm contractions, the 95% confidence interval (CI) 0.46; 3.11 and 0.73 for preterm low birth weight; 95% CI: 0.13; 4.19, respectively. CONCLUSION: In this population, periodontitis was not a detectable risk factor for preterm low birth weight in pregnant women.

Novel mutations in the cathepsin C gene in patients with pre-pubertal aggressive periodontitis and Papillon-Lefèvre syndrome.

Aggressive periodontitis (AP) in pre-pubertal children is often associated with genetic disorders like Papillon-Lefèvre syndrome (PLS). PLS is caused by mutations in the cathepsin C (CTSC) gene. We report a novel CTSC mutation (c.566-572del) in an otherwise healthy AP child and two novel compound heterozygous mutations (c.947T>G, c.1268G>C) in a PLS patient. We conclude that at least a subset of pre-pubertal AP is due to CTSC mutations and therefore may be an allelic variant of PLS.

Periodontal infections contribute to elevated systemic C-reactive protein level.

BACKGROUND: Periodontitis is a local inflammatory process mediating destruction of periodontal tissues triggered by bacterial insult. However, this disease is also characterized by systemic inflammatory host responses that may contribute, in part, to the recently reported higher risk for cardiovascular disease (CVD) among patients with periodontitis. Moderate elevation of C-reactive protein (CRP) has been found to be a predictor of increased risk for CVD. Elevated CRP levels in periodontal patients have been reported by several groups. In this study, we examined whether CRP plasma levels are increased in periodontitis and if there is a relation to severity of periodontal disease and to the periodontal microflora. METHODS: CRP serum levels were assessed using radial immunodiffusion assay in 174 subjects, 59 with moderate mean clinical attachment loss (AL) (2.39+/-0.29 mm) and 50 with high AL (3.79+/-0.86 mm) as compared to 65 periodontally healthy controls (AL, 1.74+/-0.18 mm). Clinical attachment loss, probing depths, and percentage of periodontal pocket sites > or =5 mm were measured. The presence of periodontal pathogens Porphyromonas gingivalis (P.g.), Prevotella intermedia (P.i.), Campylobacter recta (C.r.), and Bacteroides forsythus (B.f.) in subgingival plaque samples was measured by immunofluorescence microscopy. RESULTS: Statistically significant increases in CRP levels were observed in subjects with periodontal disease when compared to healthy controls (P= 0.036). Subjects with high levels of mean clinical attachment loss had significantly higher mean CRP levels (4.06+/-5.55 mg/l) than controls (1.70+/-1.91 mg/l), P= 0.011. The CRP levels were adjusted for factors known to be associated with elevated CRP, including age, smoking, body mass index (BMI), triglycerides, and cholesterol. Age and BMI were found to be significant covariates. The reported range for CRP as a risk factor for CVD, peripheral vascular diseases, or stroke is 1.34 mg/l to 6.45 mg/l and the mean of this range is 3 mg/l. The percentage of subjects with elevated levels of CRP > or = 3 mm was significantly higher in the high clinical AL group (38%; 95% Cl: 26.7%, 49.3%) when compared to the control group (16.9%; 95% CI: 9.25%, 24.5%), P= 0.011. The presence of periodontal pathogens P.g., P.i., C.r., and B.f. in subgingival samples was positively associated with elevated CRP levels (P= 0.029). CONCLUSIONS: The extent of increase in CRP levels in periodontitis patients depends on the severity of the disease after adjusting for age, smoking, body mass index, triglycerides, and cholesterol. Also, there are elevated levels of CRP associated with infection with subgingival organisms often associated with periodontal disease, including P.g., P.i., C.r., and B.f. Recent investigations emphasized the role of moderate elevated CRP plasma levels as a risk factor for CVD. The positive correlation between CRP and periodontal disease might be a possible underlying pathway in the association between periodontal disease and the observed higher risk for CVD in these patients.

Favorable long-term outcome in adult genitourinary low-grade sarcoma.

OBJECTIVES: To report our experience treating sarcomas in 20 consecutive patients. METHODS: Pretreatment and follow-up data were obtained from 20 adult patients consecutively treated between 1992 and 1998 for primary or locally recurrent genitourinary sarcoma. RESULTS: Eight patients (40%) were classified as having high-grade and 12 (60%) low-grade disease. Except for 3 patients, the primary treatment was surgery alone. The median follow-up was 52 months. The actuarial disease-specific 5-year survival rate was 84% in all patients and was 100% for patients with Memorial Sloan Kettering Cancer Center (MSKCC) Stages 1-2 and 54% in MSKCC Stages 3-4. The disease-specific survival was significantly better in low-grade tumors (log-rank test, P = 0.0063) and inguinal-scrotal tumors (P = 0.019), tumors 5 cm or less (P = 0.039), and MSKCC Stages 1-2 tumors (P = 0.0035). CONCLUSIONS: The results of this study with a high proportion of low-grade, low-stage, and inguinal-scrotal sarcomas demonstrate the favorable prognosis of these subgroups.

Metabolic diseases and their possible link to risk indicators of periodontitis.

BACKGROUND: During the last few years, risk assessment has become one of the main topics of periodontal research. Therefore, the aim of this study was to determine whether a predisposition to metabolic disorders such as diabetes mellitus (in the absence of diagnosed diabetic disease) or hyperlipidemia may be risk indicators for periodontitis. METHODS: One hundred patients ranging in age from 40 to 70 years were examined. The patients were classified as having impaired glucose tolerance (IGT) but no manifest diabetes (56 patients), hyperlipidemia (17 patients, HL), or normal metabolic status (27 control patients). Probing depth (PD), attachment level (AL), plaque index (PI), and gingival bleeding on probing (BOP) were recorded. Serum antibody titers (SAT) to A. actinomycetemcomitans (A.a.), P. intermedia (P.i.), and P. gingivalis (P.g.) were determined by enzyme-linked immunosorbent assay (ELISA). Pooled subgingival plaque samples were analyzed using indirect immunofluorescence to detect the same organisms. In addition, respiratory burst activity of peripheral polymorphonuclear leukocytes (PMN) was evaluated by chemiluminescence (CL). RESULTS: No significant differences were observed between the IGT group and normal controls in the following parameters: 1) percentage of sites exhibiting BOP; 2) mean PI; 3) mean PD and AL; 4) percentage of periodontal microorganisms; and 5) increased SAT. The IGT probands exhibited a significantly higher mean serum level of triglycerides, as well as higher formyl-methionyl-leucyl-phenylalanine (FMLP)-stimulated PMN chemiluminescence than the control group. Patients with hyperlipidemia (HL) showed a significantly higher number of sextants with increased PD (73.4%) than the control group (50.6%). Similar results were obtained when comparing the percentage of all sites with increased PD (HL = 16.7%, control 12.3%). The mean FMLP-stimulated CL in patients with hyperlipidemia was significantly higher than the control group. When looking at all patients, there was a small but statistically significant correlation between PD and lipid levels. In addition, a significant correlation was observed between lipid serum levels and the FMLP-stimulated chemiluminescence. CONCLUSIONS: These findings suggest that abnormal glucose tolerance, which is a predisposing factor for diabetes mellitus, does not appear to be a risk indicator for periodontal disease. On the other hand, impaired lipid metabolism does seem to be a risk indicator for periodontitis.

Intratesticular leiomyosarcoma in a young man after high dose doping with Oral-Turinabol: a case report.

BACKGROUND: Androgenic anabolic steroids have been suspected of activity as carcinogens in the development of carcinoma and angiosarcoma of the liver and adenocarcinoma of the prostate. Although the proliferation of smooth muscle cells is stimulated by sexual steroids, to the authors' knowledge a possible relation between androgenic anabolic steroids and the development of leiomyosarcoma has not previously been reported in humans. METHODS: A 32-year-old man underwent right radical orchiectomy for a tumor of the upper pole of the right testicle. Routine histopathologic examination and immunohistochemical staining were performed. RESULTS: The tumor was identified as an intratesticular leiomyosarcoma based on its typical growth pattern and the characteristic immunohistochemical staining profile. The patient reported a 5-year history of systematic use of high dose Oral-Turinabol (4-chloro-1-dehydro-17alpha-methylteststerone) that began at age 18 years and stopped approximately 9 years before presentation. CONCLUSIONS: The rarity of intratesticular leiomyosarcoma, the experimental induction of similar tumors in animals by androgens and estrogens, and the unusually young age at presentation of the patient in the current study support the hypothesis that high dose doping with androgenic anabolic steroids could have played a cocarcinogenic role in the development of the tumor in this case.

Platelet aggregation inhibiting and anticoagulant effects of oligoamines, XVI: Cytostatic and cytotoxic side effects of oligoamines.

Selected synthetic oligoamines were able to inhibit (IC50) the growth of leukemic L 1210 cells in concentrations between 4-10 mumol/L. The essential structural features were at least two basic nitrogen functions in suitable distance, substituted with arylalkyl or alkyl groups. The favorable chain length is about eight carbon atoms. The cytostatic effect is complete after 30 min and cannot be washed out with buffer. Viability measurements showed that the leukemic cells were killed in a time dependent manner. As no influence on the cell nucleus could be observed this is most probably due to interaction with the cell membrane. When high local concentrations are applied in vivo, the oligoamines are toxic because of cytolytic properties. This toxicity can be overcome by administration of suitable prodrugs (LD50 greater than 1000 mg/kg).

[Modified bridge flap. Three-year control study]. / Eine modifizierte Brückenlappenplastik. Ergebnisse einer dreijährigen Verlaufskontrolle.

Gingival recessions in the upper jaw were covered by a modified bridging flap and follow-up examinations were carried out over three years. After one year the covering result was 72% and after three years 66%.