| 1. |
- Mäntylä, Päivi, et al.
(författare)
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Subgingival Aggregatibacter actinomycetemcomitans associates with the risk of coronary artery disease
- 2013
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Ingår i: Journal of Clinical Periodontology. - 0303-6979 .- 1600-051X. ; 40:6, s. 583-590
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Tidskriftsartikel (refereegranskat)abstract
- Aim We investigated the association between angiographically verified coronary artery disease (CAD) and subgingival Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. Materials and Methods The cross-sectional study population (n = 445) comprised 171 (38.4%) patients with Stable CAD, 158 (35.5%) with acute coronary syndrome (ACS) and 116 (26.1%) with no significant CAD (No CAD). All patients participated in clinical and radiological oral health examinations. Pooled subgingival bacterial samples were analysed by checkerboard DNA–DNA hybridization assays. Results In all study groups, the presence of P. gingivalis, T. forsythia and T. denticola indicated a significant (p ≤ 0.001) linear association with the extent of alveolar bone loss (ABL), but A. actinomycetemcomitans did not (p = 0.074). With a threshold level of bacterial cells 1 × 105 A. actinomycetemcomitans was significantly more prevalent in the Stable CAD group (42.1%) compared to the No CAD group (30.2%) (p = 0.040). In a multi-adjusted logistic regression analysis using this threshold, A. actinomycetemcomitans positivity associated with Stable CAD (OR 1.83, 95% CI 1.00–3.35, p = 0.049), but its level or levels of other bacteria did not. Conclusions The presence of subgingival A. actinomycetemcomitans associates with an almost twofold risk of Stable CAD independently of alveolar bone loss.
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| 2. |
- Pradhan-Palikhe, Pratikshya, et al.
(författare)
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Subgingival bacterial burden in relation to clinical and radiographic periodontal parameters.
- 2013
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Ingår i: Journal of periodontology. - 1943-3670. ; 84:12, s. 1809-1817
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: This cross-sectional study characterizes the association between subgingival bacterial profile and periodontal parameters in patients assigned to coronary angiography because of cardiologic problems, which may affect the oral microbiota.METHODS: Pooled subgingival bacterial samples were collected from 477 dentate individuals during the oral examinations, along with periodontal probing depth (PD) and assessments of bleeding on probing (BOP) and radiographic alveolar bone loss (ABL). The checkerboard DNA-DNA hybridization assay was used to determine the levels of 29 oral bacteria, which were divided into three bacterial complexes.RESULTS: All bacterial combinations from the etiologic bacterial group and each species from the red complex were significantly associated (P <0.001) with grade of ABL. The prevalence of the etiologic bacterial group and the level of each species were also associated strongly with the proportion of sites with PD 4 to 5 mm and ≥ 6 mm, BOP, and ABL, except Aggregatibacter actinomycetemcomitans. Levels of Gram-negative oral bacteria correlated significantly with those of Gram-positive species (r = 0.840, P <0.001). In multiple logistic regression analysis, the prevalence of the etiologic bacterial group, levels of Gram-negative bacteria and Treponema denticola, and the prevalence of Porphyromonas gingivalis and T. denticola associated significantly with ABL, whereas other bacterial complexes and levels of Gram-positive species did not.CONCLUSIONS: Although levels of Gram-negative and -positive species paralleled periodontal parameters, only the species considered etiologic were associated with ABL.
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| 3. |
- Aberg, Carola Höglund, et al.
(författare)
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Presence of Aggregatibacter actinomycetemcomitans in young individuals : a 16-year clinical and microbiological follow-up study.
- 2009
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Ingår i: Journal of clinical periodontology. - 1600-051X. ; 36:10, s. 815-22
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To look for clinical signs of periodontal disease in young adults who exhibited radiographic bone loss and detectable numbers of Aggregatibacter actinomycetemcomitans in their primary dentition. MATERIAL AND METHODS: Periodontal status and radiographic bone loss were examined in each of the subjects 16 years after the baseline observations. Techniques for anaerobic and selective culture, and checkerboard, were used to detect periodontitis-associated bacterial species. The isolated A. actinomycetemcomitans strains were characterized by polymerase chain reaction. RESULTS: Signs of localized attachment loss were found in three out of the 13 examined subjects. A. actinomycetemcomitans was recovered from six of these subjects and two of these samples were from sites with deepened probing depths and attachment loss. Among the isolated A. actinomycetemcomitans strains, serotypes a-c and e, but not d or f, were found. None of the isolated strains belonged to the highly leucotoxic JP2 clone, and one strain lacked genes for the cytolethal distending toxin. CONCLUSIONS: This study indicates that the presence of A. actinomycetemcomitans and early bone loss in the primary dentition does not necessarily predispose the individual to periodontal attachment loss in the permanent dentition.
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| 4. |
- Akhi, Ramin, et al.
(författare)
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Cross-reactive saliva IgA antibodies to oxidized LDL and periodontal pathogens in humans.
- 2017
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Ingår i: Journal of Clinical Periodontology. - : Wiley. - 0303-6979 .- 1600-051X. ; 44:7, s. 682-691
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Tidskriftsartikel (refereegranskat)abstract
- AIM: Oxidized low-density lipoproteins (oxLDL) are formed as a result of lipid peroxidation and are highly immunogenic and proatherogenic. In this study, saliva antibodies binding to oxLDL, Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa) were characterized and their cross-reactivity was evaluated.MATERIALS AND METHODS: Resting and stimulated saliva samples were collected from 36 healthy adults (mean age 26 years). Saliva IgA, IgG and IgM autoantibody levels to copper oxidized LDL (CuOx-LDL) and malondialdehyde acetaldehyde-modified LDL (MAA-LDL) were determined with chemiluminescence immunoassay.RESULTS: Saliva IgA and IgG antibodies binding to MAA-LDL and CuOx-LDL were detected in all samples and they were associated with the saliva levels of IgA and IgG to P. gingivalis and A. actinomycetemcomitans. Competitive immunoassay showed that saliva antibodies to MAA-LDL cross-reacted specifically with P. gingivalis. The autoantibody levels to oxLDL in saliva were not associated with the autoantibody levels to oxLDL in plasma or with saliva apolipoprotein B 100 levels.CONCLUSIONS: Saliva contains IgA and IgG binding to oxLDL, which showed cross-reactive properties with the periodontal pathogens Porphyromonas gingivalis (P.g). The data suggest that secretory IgA to P.g may participate in immune reactions involved in LDL oxidation through molecular mimicry.
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| 5. |
- Buhlin, Kare, et al.
(författare)
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Association of periodontitis with persistent, pro-atherogenic antibody responses
- 2015
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Ingår i: Journal of Clinical Periodontology. - : Wiley-Blackwell. - 0303-6979 .- 1600-051X. ; 42:11, s. 1006-1014
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Tidskriftsartikel (refereegranskat)abstract
- AIM: To study antibody responses associated with molecular mimicry in periodontitis.MATERIAL AND METHODS: Fifty-four periodontitis cases (mean age 54.0 years) and 44 controls (53.6 years) were examined, after which cases received periodontal treatment. Established immunoassays were used to analyse levels of antibodies against two pathogens, Aggregatibacter actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg), heat shock proteins (Hsp), Hsp60, Hsp65, and Hsp70, and epitopes of oxidized low density lipoprotein (oxLDL) (CuOx-LDL and MDA-LDL) in plasma samples that were collected at baseline, after 3 (n=48) and 6 (n=30) months.RESULTS: When age, sex, smoking habit, and the number of teeth were considered in multivariate logistic regressions, Aa and Pg IgG, Hsp65-IgA, CuOx-LDL-IgG and -IgM and MDA-LDL-IgG antibody levels were associated with periodontitis, whereas Hsp60-IgG2 antibody levels were inversely associated. The Aa antibody levels significantly correlated with the levels of IgA antibodies to Hsp65 and Hsp70, and both OxLDL IgA-antibody levels. The levels of antibodies to Pg correlated with IgG antibodies to Hsp60, Hsp70 and both oxLDL antibody epitopes. None of the antibody levels changed significantly after treatment.CONCLUSIONS: Periodontitis is associated with persistently high levels of circulating antibodies that are reactive with pathogen- and host-derived antigens.
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| 6. |
- Holmlund, Anders, et al.
(författare)
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Porphyromonas gingivalis (Pg) a possible link between impaired oral health and acute myocardial infarction
- 2011
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 148:2, s. 148-153
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To investigate if oral health parameters were impaired in patients with myocardial infarction (MI) and if there was an association with serum antibody levels against the periodontal pathogens Porphyromonas gingivalis (Pg) and Aggregatibacter actinomycetemcomitans (Aa). Methods: A case-control study consisting of 100 patients with MI and 100 age- and sex-matched controls from the same geographic area was investigated regarding oral health. Results: The MI group had significantly more periodontal bone loss (PBL), number of deepened pockets (NDP), and bleeding on probing (BOP), and lower number of teeth (NT) than the controls. After adjustment for known cardiovascular risk factors NT, BOP, and NDP still remained significantly related to MI (p = 0.014, p = 0.02, and p = 0.0069, respectively). IgG antibody levels against Pg were higher in subjects with MI (p = 0.043), as well as in those with > 4 deepened pockets (p = 0.05), BOP > 20% (p = 0.001) and PBL (p = 0.0003). However, indicating a causal pathway, the relationship between MI and Pg IgG disappeared when the oral parameters were included in the logistic regression model (p = 0.69). No correlation was seen between MI and Aa in the present study. Conclusion: Patients with MI had an impaired oral health compared to controls. Furthermore, IgG levels against Pg were related to both MI and oral health, suggesting this pathogen as a possible link between oral health and CVD.
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| 7. |
- Johansson, Anders, 1955-, et al.
(författare)
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Systemic Aggregatibacter Actinomycetemccomitans Leukotoxin-Neutralizing Antibodies in Periodontitis
- 2017
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Ingår i: Journal of Periodontology. - : Wiley. - 0022-3492 .- 1943-3670. ; 88:1, s. 122-129
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The leukotoxin expressed by Aggregatibacter actinomycetemcomitans is a powerful exotoxin, which can cause imbalance in the host response. Immunoreactivity to the leukotoxin is a marker for the presence of leukotoxic A. actinomycetemcomitan, a presence that may modify the disease pattern of the colonized individuals. The aim of the present study was to examine the presence of systemic immunoreactivity to A. actionmycetemcomitans leukotoxin in relation to clinical and inflammatory findings in individuals with or without periodontitis (n = 88).METHODS: The periodontal status was examined in a population of cases (n = 49) and controls (n = 39), and the cases received periodontal treatment. Systemic biomarkers associated with inflammation and infections, as well as the clinical parameters, were analyzed at baseline, three months after treatment and six months after.RESULTS: The presence of immunoreactivity against leukotoxin was associated with impaired remission of the disease after periodontal treatment. This immunoreactivity was also significantly associated with increased systemic levels of A. actinomycetemcomtans-specific immunoglobulins and increasing age.CONCLUSION: The presence and levels of systemic immunoreactivity against A. actinomycetemcomitans leukotoxin are associated with a decreased remission after otherwise successful periodontal treatment.
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| 8. |
- Karhu, Elisa, et al.
(författare)
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Exercise and gastrointestinal symptoms : running-induced changes in intestinal permeability and markers of gastrointestinal function in asymptomatic and symptomatic runners
- 2017
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Ingår i: European Journal of Applied Physiology. - : Springer. - 1439-6319 .- 1439-6327. ; 117:12, s. 2519-2526
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Tidskriftsartikel (refereegranskat)abstract
- Athletes frequently experience gastrointestinal (GI) symptoms during training and competition. Although the prevalence of exercise-induced GI symptoms is high, the mechanisms leading to GI distress during exercise are not fully understood. The aim of this study was to identify running-induced changes in intestinal permeability and markers of GI function and investigate their association with gastrointestinal symptoms. We recruited 17 active runners who we allocated as either asymptomatic or symptomatic based on their history of experiencing GI symptoms during running. The participants took part in a running test where they were asked to run for 90 min at 80% of their best 10 km race speed. Intestinal permeability was measured at baseline and after the running test. Levels of serum intestinal fatty acid-binding protein (I-FABP), zonulin, bacterial lipopolysaccharide (LPS), and fecal calprotectin were also measured at baseline and after the running test. Running induced a significant increase in intestinal permeability and serum I-FABP concentration but there were no differences between asymptomatic and symptomatic runners. Serum LPS activity did not change from baseline following the running test but the symptomatic group exhibited higher LPS activity at baseline compared to the asymptomatic runners. Running for 90 min at a challenging pace causes small intestinal damage and increases intestinal permeability. However, these alterations in GI function do not appear to correlate with the development of GI symptoms during running.
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| 9. |
- Kopra, Elisa, et al.
(författare)
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Systemic Antibiotics Influence Periodontal Parameters and Oral Microbiota, But Not Serological Markers
- 2021
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Ingår i: Frontiers in Cellular and Infection Microbiology. - : Frontiers Media S.A.. - 2235-2988. ; 11, s. 1-12
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Tidskriftsartikel (refereegranskat)abstract
- The use of systemic antibiotics may influence the oral microbiota composition. Our aim was to investigate in this retrospective study whether the use of prescribed antibiotics associate with periodontal status, oral microbiota, and antibodies against the periodontal pathogens. The Social Insurance Institution of Finland Data provided the data on the use of systemic antibiotics by record linkage to purchased medications and entitled reimbursements up to 1 year before the oral examination and sampling. Six different classes of antibiotics were considered. The Parogene cohort included 505 subjects undergoing coronary angiography with the mean (SD) age of 63.4 (9.2) years and 65% of males. Subgingival plaque samples were analysed using the checkerboard DNA-DNA hybridisation. Serum and saliva antibody levels to periodontal pathogens were analysed with immunoassays and lipopolysaccharide (LPS) activity with the LAL assay. Systemic antibiotics were prescribed for 261 (51.7%) patients during the preceding year. The mean number of prescriptions among them was 2.13 (range 1–12), and 29.4% of the prescriptions were cephalosporins, 25.7% penicillins, 14.3% quinolones, 12.7% macrolides or lincomycin, 12.0% tetracycline, and 5.8% trimethoprim or sulphonamides. In linear regression models adjusted for age, sex, current smoking, and diabetes, number of antibiotic courses associated significantly with low periodontal inflammation burden index (PIBI, p < 0.001), bleeding on probing (BOP, p = 0.006), and alveolar bone loss (ABL, p = 0.042). Cephalosporins associated with all the parameters. The phyla mainly affected by the antibiotics were Bacteroidetes and Spirochaetes. Their levels were inversely associated with the number of prescriptions (p = 0.010 and p < 0.001) and directly associated with the time since the last prescription (p = 0.019 and p < 0.001). Significant inverse associations were observed between the number of prescriptions and saliva concentrations of Prevotella intermedia, Tannerella forsythia, and Treponema denticola and subgingival bacterial amounts of Porphyromonas gingivalis, P. intermedia, T. forsythia, and T. denticola. Saliva or serum antibody levels did not present an association with the use of antibiotics. Both serum (p = 0.031) and saliva (p = 0.032) LPS activity was lower in patients having any antibiotic course less than 1 month before sampling. Systemic antibiotics have effects on periodontal inflammation and oral microbiota composition, whereas the effects on host immune responses against the periodontal biomarker species seem unchanged.
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| 10. |
- Kyrklund, Mikael, et al.
(författare)
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Immunization with gingipain A hemagglutinin domain of Porphyromonas gingivalis induces IgM antibodies binding to malondialdehyde-acetaldehyde modified low-density lipoprotein.
- 2018
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 13:1
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Tidskriftsartikel (refereegranskat)abstract
- Treatment of periodontitis has beneficial effects on systemic inflammation markers that relate to progression of atherosclerosis. We aimed to investigate whether immunization with A hemagglutinin domain (Rgp44) of Porphyromonas gingivalis (Pg), a major etiologic agent of periodontitis, would lead to an antibody response cross-reacting with oxidized low-density lipoprotein (OxLDL) and how it would affect the progression of atherosclerosis in low-density lipoprotein receptor-deficient (LDLR-/-) mice. The data revealed a prominent IgM but not IgG response to malondialdehyde-acetaldehyde modified LDL (MAA-LDL) after Rgp44 and Pg immunizations, implying that Rgp44/Pg and MAA adducts may share cross-reactive epitopes that prompt IgM antibody production and consequently confer atheroprotection. A significant negative association was observed between atherosclerotic lesion and plasma IgA to Rgp44 in Rgp44 immunized mice, supporting further the anti-atherogenic effect of Rgp44 immunization. Plasma IgA levels to Rgp44 and to Pg in both Rgp44- and Pg-immunized mice were significantly higher than those in saline control, suggesting that IgA to Rgp44 could be a surrogate marker of immunization in Pg-immunized mice. Distinct antibody responses in plasma IgA levels to MAA-LDL, to Pg lipopolysaccharides (Pg-LPS), and to phosphocholine (PCho) were observed after Rgp44 and Pg immunizations, indicating that different immunogenic components between Rpg44 and Pg may behave differently in regard of their roles in the development of atherosclerosis. Immunization with Rgp44 also displayed atheroprotective features in modulation of plaque size through association with plasma levels of IL-1α whereas whole Pg bacteria achieved through regulation of anti-inflammatory cytokine levels of IL-5 and IL-10. The present study may contribute to refining therapeutic approaches aiming to modulate immune responses and inflammatory/anti-inflammatory processes in atherosclerosis.
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| 11. |
- Mäntylä, Päivi, et al.
(författare)
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Subgingival Aggregatibacter actinomycetemcomitans associates with the risk of coronary artery disease
- 2013
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Ingår i: Journal of Clinical Periodontology. - : Blackwell Munksgaard. - 0303-6979 .- 1600-051X. ; 40:6, s. 583-590
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Tidskriftsartikel (refereegranskat)abstract
- Aim We investigated the association between angiographically verified coronary artery disease (CAD) and subgingival Aggregatibacter actinomycetemcomitans, Porphyromonas gingivalis, Tannerella forsythia and Treponema denticola. Materials and Methods The cross-sectional study population (n = 445) comprised 171 (38.4%) patients with Stable CAD, 158 (35.5%) with acute coronary syndrome (ACS) and 116 (26.1%) with no significant CAD (No CAD). All patients participated in clinical and radiological oral health examinations. Pooled subgingival bacterial samples were analysed by checkerboard DNA–DNA hybridization assays. Results In all study groups, the presence of P. gingivalis, T. forsythia and T. denticola indicated a significant (p ≤ 0.001) linear association with the extent of alveolar bone loss (ABL), but A. actinomycetemcomitans did not (p = 0.074). With a threshold level of bacterial cells 1 × 105 A. actinomycetemcomitans was significantly more prevalent in the Stable CAD group (42.1%) compared to the No CAD group (30.2%) (p = 0.040). In a multi-adjusted logistic regression analysis using this threshold, A. actinomycetemcomitans positivity associated with Stable CAD (OR 1.83, 95% CI 1.00–3.35, p = 0.049), but its level or levels of other bacteria did not. Conclusions The presence of subgingival A. actinomycetemcomitans associates with an almost twofold risk of Stable CAD independently of alveolar bone loss.
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| 12. |
- Odermarsky, Michal, et al.
(författare)
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HLA, infections and inflammation in early stages of atherosclerosis in children with type 1 diabetes
- 2018
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Ingår i: Acta Diabetologica. - : Springer Science and Business Media LLC. - 1432-5233 .- 0940-5429. ; 55:1, s. 41-47
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Tidskriftsartikel (refereegranskat)abstract
- Aims This prospective study focuses on risk factors for arterial damage in children with type 1 diabetes (T1D). Methods Eighty children and adolescents with T1D were investigated twice, approximately 2 years apart, for carotid artery intima-media thickness (cIMT) and compliance (CAC), flow-mediated dilatation (FMD) of the brachial artery, and plasma levels of matrix metalloproteinase (MMP)-8. All subjects were genotyped for HLA. The number of respiratory tract infections (RTI) during the past year was obtained by a questionnaire in 56 patients. Results cIMT progression, defined as percentage (%) change of cIMT from baseline, correlated inversely with the % changes of both CAC (p = 0.04, r = − 0.3; n = 62) and FMD (p = 0.03, r = − 0.3; n = 47). In multivariate analysis, RTI frequency correlated significantly with cIMT progression irrespective of age, diabetes duration, BMI, and HbA1c (p = 0.03, r = 0.3). When patients were divided in relation to RTI, the association of DQ2/8 with cIMT progression remained significant in patients with over three infections/year (p = 0.04, r = 0.3). During follow-up, the group of DQ2/8 patients with hsCRP > 1 mg/l showed significantly higher levels of plasma MMP-8 than the non-DQ2/8 group. Conclusions The diabetes-risk genotype DQ2/8 and systemic inflammation contribute to pro-atherosclerotic vascular changes in children and adolescents with T1D.
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| 13. |
- Odermarsky, M., et al.
(författare)
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Human Leucocyte Antigen, Infections and Systemic Inflammatory Biomarkers in Early Atherosclerosis in Children and Adolescents with Type 1 Diabetes
- 2015
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Ingår i: Cardiology in the Young. - 1467-1107. ; 25:Suppl. 1, s. 33-33
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Konferensbidrag (refereegranskat)abstract
- Background: This prospective study focuses on factors associated with arterial damage in children with type 1 diabetes (T1D). Materials and Methods: Eighty children and adolescents with T1D (mean age 15, range: 8-20 yrs; mean diabetes duration 7, range: 0.5 to 19 years) were investigated twice, approximately 2 years apart, for carotid artery intima-media thickness (cIMT) and compliance (CAC), flow-mediated dilatation (FMD) of the brachial artery, and plasma levels of matrix metalloproteinase (MMP)-8. HLA genotypes were determined in dried spots of peripheral blood by polymerase chain reaction followed by hybridization assay. The number of respiratory tract infections (RTI) during the past year was obtained by a questionnaire in 56 patients. Results: cIMT progression (% change of cIMT from baseline) correlated inversely with the % changes of both CAC (p = 0.04, r=−0.3, n=62) and FMD (p=0.03, r=−0.3, n=67). RTI frequency correlated significantly with cIMT progression irre- spective of age, diabetes duration, BMI, and HbA1c (p=0.03, r=0.3, in multivariate analysis). When patients were divided in relation to DQ2/8 genotype and RTI, the association of DQ2/8 with cIMT progression remained significant in patients with over three infections/year (p = 0.04, r = 0.3). During follow-up, the group of DQ2/8 patients with CRP > 1 mg/l showed significantly higher levels of plasma MMP-8 than the non-DQ2/8 group. Conclusions: Diabetes-risk genotype DQ2/8 and inflammation con- tribute to vascular changes in children and adolescents with T1D.
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| 14. |
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| 15. |
- Pesonen, Erkki, et al.
(författare)
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Infections as a stimulus for coronary occlusion, obstruction, or acute coronary syndromes.
- 2009
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Ingår i: Therapeutic Advances in Cardiovascular Disease. - : SAGE Publications. - 1753-9447 .- 1753-9455.
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: : Atherosclerosis is considered to be an inflammatory disease. Infections are a significant cause of inflammation. Acute infections might precipitate acute coronary syndromes (ACS) whereas chronic infections might be stimuli for the development of atherosclerosis. METHODS: : Coronary angiograms were done on 211 of 335 patients with ACS and the percentage of coronary obstruction was determined. Serum antibody levels to Chlamydia pneumoniae, C. pneumoniae heat shock protein 60 (CpnHSP60), human heat shock protein 60 (hHSP60), enterovirus (EV), herpes simplex virus (HSV), cytomegalovirus (CMV), and two major periodontal pathogens, Aggregatibacter actinomycetemcomitans and Porphyromonas gingivalis, were measured in healthy controls (n = 355) and all patients. RESULTS: : Serum antibody levels to periodontal pathogens did not correlate with ACS. However, IgA-class antibody levels to Aggregatibacter actinomycetemcomitans (p = 0.021), CpnHSP60 (p = 0.048) an hHSP60 (p = 0.038) were higher in patients with coronary occlusion or obstruction compared to those without any obstruction. Odds ratios for coronary changes in the highest quartile as compared to the lower quartiles were for A. actinomycetemcomitans IgA 7.84 (95% CI 1.02-60.39, p = 0.048), for CpnHSP60 IgA 8.61 (1.12-65.89, p = 0.038), and for human HSP60 IgA 3.51 (0.79-15.69, p = 0.100). CONCLUSIONS: : We have previously reported that EV and HSV titres correlated significantly to acute coronary events. They do not correlate to the degree of coronary obstruction as shown here. However, infection by A. actinomycetemcomitans or C. pneumoniae or host response against them associated with coronary obstruction. Clinical coronary events may arise by the effect of acute infections and obstructing lesions by a chronic inflammatory stimulus.
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| 16. |
- Pietiäinen, Milla, et al.
(författare)
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Saliva and Serum Immune Responses in Apical Periodontitis
- 2019
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Ingår i: Journal of Clinical Medicine. - Basel, Switzerland : MDPI. - 2077-0383. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- Apical periodontitis is an inflammatory reaction at the apex of an infected tooth. Its microbiota resembles that of marginal periodontitis and may induce local and systemic antibodies binding to bacteria- and host-derived epitopes. Our aim was to investigate the features of the adaptive immune response in apical periodontitis. The present Parogene cohort (n = 453) comprises patients with cardiac symptoms. Clinical and radiographic oral examination was performed to diagnose apical and marginal periodontitis. A three-category endodontic lesion score was designed. Antibodies binding to the bacteria- and host-derived epitopes were determined from saliva and serum, and bacterial compositions were examined from saliva and subgingival samples. The significant ORs (95% CI) for the highest endodontic scores were observed for saliva IgA and IgG to bacterial antigens (2.90 (1.01-8.33) and 4.91 (2.48-9.71)/log10 unit), saliva cross-reacting IgG (2.10 (1.48-2.97)), serum IgG to bacterial antigens (4.66 (1.22-10.1)), and Gram-negative subgingival species (1.98 (1.16-3.37)). In a subgroup without marginal periodontitis, only saliva IgG against bacterial antigens associated with untreated apical periodontitis (4.77 (1.05-21.7)). Apical periodontitis associates with versatile adaptive immune responses against both bacterial- and host-derived epitopes independently of marginal periodontitis. Saliva immunoglobulins could be useful biomarkers of oral infections including apical periodontitis-a putative risk factor for systemic diseases.
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| 17. |
- Pussinen, Pirkko J., et al.
(författare)
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The balance of serum matrix metalloproteinase-8 and its tissue inhibitor in acute coronary syndrome and its recurrence
- 2013
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 167:2, s. 362-368
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Tidskriftsartikel (refereegranskat)abstract
- Background: Matrix metalloproteinase-8 (MMP-8) is involved in the breakdown of the extracellular matrix increasing the vulnerability of atherosclerotic lesions. We analysed the diagnostic value of serum MMP-8 and tissue inhibitor of metalloproteinase-1 (TIMP-1) concentrations in acute coronary syndrome (ACS) and their prognostic value in ACS recurrence. Methods: The population comprised 343 patients with ACS [including 108 unstable angina pectoris and 235 acute myocardial infarctions (AMI)] and 326 healthy controls. Additionally, 157 (45.8%) patients were resampled during the recovery. The ACS patients were followed up for 6 years. Results: MMP-8, TIMP-1, and their molar ratio distinguished the cases from the controls; C-statistic of the multivariate model (95% CI, p-value) including the MMP-8/TIMP-1 ratio regarding its discriminating ability for AMI was 0.922 (0.893-0.950, p < 0.001). After the acute phase of ACS, median MMP-8 and TIMP-1 concentrations decreased (p < 0.001) by 34.5 and 28.7%, respectively, but ended up on a different level than those found in the controls. In the follow-up, acute phase and recovery period TIMP-1 concentrations associated with cardiovascular death with hazard ratios 4.31 (2.00-9.26, p < 0.001) and 4.69 (1.10-20.01, p = 0.037), respectively. Conclusions: The increase of serum MMP-8 and TIMP-1 concentrations may reflect plaque instability and tissue damage. TIMP-1 concentrations are associated with poor outcome in patients with ACS. The findings may have practical implications in both diagnostics and therapeutics. (c) 2011 Elsevier Ireland Ltd. All rights reserved.
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| 18. |
- Putaala, Jukka, et al.
(författare)
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Searching for Explanations for Cryptogenic Stroke in the Young : Revealing the Triggers, Causes, and Outcome (SECRETO): Rationale and design
- 2017
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Ingår i: European Stroke Journal. - : SAGE Publications. - 2396-9873 .- 2396-9881. ; 2:2, s. 116-125
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Tidskriftsartikel (refereegranskat)abstract
- Background: Worldwide, about 1.3 million annual ischaemic strokes (IS) occur in adults aged <50 years. Of these early-onset strokes, up to 50% can be regarded as cryptogenic or associated with conditions with poorly documented causality like patent foramen ovale and coagulopathies. Key hypotheses/aims: (1) Investigate transient triggers and clinical/sub-clinical chronic risk factors associated with cryptogenic IS in the young; (2) use cardiac imaging methods exceeding state-of-the-art to reveal novel sources for embolism; (3) search for covert thrombosis and haemostasis abnormalities; (4) discover new disease pathways using next-generation sequencing and RNA gene expression studies; (5) determine patient prognosis by use of phenotypic and genetic data; and (6) adapt systems medicine approach to investigate complex risk-factor interactions. Design: Searching for Explanations for Cryptogenic Stroke in the Young: Revealing the Etiology, Triggers, and Outcome (SECRETO; NCT01934725) is a prospective multi-centre case–control study enrolling patients aged 18–49 years hospitalised due to first-ever imaging-proven IS of undetermined etiology. Patients are examined according to a standardised protocol and followed up for 10 years. Patients are 1:1 age- and sex-matched to stroke-free controls. Key study elements include centralised reading of echocardiography, electrocardiography, and neurovascular imaging, as well as blood samples for genetic, gene-expression, thrombosis and haemostasis and biomarker analysis. We aim to have 600 patient–control pairs enrolled by the end of 2018. Summary: SECRETO is aiming to establish novel mechanisms and prognosis of cryptogenic IS in the young and will provide new directions for therapy development for these patients. First results are anticipated in 2019.
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| 19. |
- Turunen, S. Pauliina, et al.
(författare)
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Immunization with malondialdehyde-modified low-density lipoprotein (LDL) reduces atherosclerosis in LDL receptor-deficient mice challenged with Porphyromonas gingivalis
- 2015
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Ingår i: Innate Immunity. - : SAGE Publications. - 1753-4259 .- 1753-4267. ; 21:4, s. 370-85
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Tidskriftsartikel (refereegranskat)abstract
- Periodontal infections increase the risk of atherosclerotic vascular disease via partly unresolved mechanisms. Of the natural IgM Abs that recognize molecular mimicry on bacterial epitopes and modified lipid and protein structures, IgM directed against oxidized low-density lipoprotein (LDL) is associated with atheroprotective properties. Here, the effect of natural immune responses to malondialdehyde-modified LDL (MDA-LDL) in conferring protection against atherosclerosis, which was accelerated by the major periodontopathogen Porphyromonas gingivalis, was investigated. LDL receptor-deficient (LDLR(-/-)) mice were immunized with mouse MDA-LDL without adjuvant before topical application challenge with live P. gingivalis. Atherosclerosis was analyzed after a high-fat diet, and plasma IgG and IgM Ab levels were measured throughout the study, and the secretion of IL-5, IL-10 and IFN-γ in splenocytes stimulated with MDA-LDL was determined. LDLR(-/-) mice immunized with MDA-LDL had elevated IgM and IgG levels to MDA-LDL compared with saline-treated controls. MDA-LDL immunization diminished aortic lipid depositions after challenge with P. gingivalis compared with mice receiving only P. gingivalis challenge. Immunization of LDLR(-/-) mice with homologous MDA-LDL stimulated the production of IL-5, implicating general activation of B-1 cells. Immune responses to MDA-LDL protected from the P. gingivalis-accelerated atherosclerosis. Thus, the linkage between bacterial infectious burden and atherogenesis is suggested to be modulated via natural IgM directed against cross-reactive epitopes on bacteria and modified LDL.
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| 20. |
- Turunen, S. Pauliina, et al.
(författare)
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Recognition of Porphyromonas gingivalis gingipain epitopes by natural IgM binding to malondialdehyde modified low-density lipoprotein.
- 2012
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Ingår i: PLOS ONE. - : Public Library Science. - 1932-6203. ; 7:4
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Increased risk for atherosclerosis is associated with infectious diseases including periodontitis. Natural IgM antibodies recognize pathogen-associated molecular patterns on bacteria, and oxidized lipid and protein epitopes on low-density lipoprotein (LDL) and apoptotic cells. We aimed to identify epitopes on periodontal pathogen Porphyromonas gingivalis recognized by natural IgM binding to malondialdehyde (MDA) modified LDL.METHODS AND RESULTS: Mouse monoclonal IgM (MDmAb) specific for MDA-LDL recognized epitopes on P. gingivalis on flow cytometry and chemiluminescence immunoassays. Immunization of C57BL/6 mice with P. gingivalis induced IgM, but not IgG, immune response to MDA-LDL and apoptotic cells. Immunization of LDLR(-/-) mice with P. gingivalis induced IgM, but not IgG, immune response to MDA-LDL and diminished aortic lipid deposition. On Western blot MDmAb bound to P. gingivalis fragments identified as arginine-specific gingipain (Rgp) by mass spectrometry. Recombinant domains of Rgp produced in E. coli were devoid of phosphocholine epitopes but contained epitopes recognized by MDmAb and human serum IgM. Serum IgM levels to P. gingivalis were associated with anti-MDA-LDL levels in humans.CONCLUSION: Gingipain of P. gingivalis is recognized by natural IgM and shares molecular identity with epitopes on MDA-LDL. These findings suggest a role for natural antibodies in the pathogenesis of two related inflammatory diseases, atherosclerosis and periodontitis.
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| 21. |
- Wang, Chunguang, et al.
(författare)
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Characterization of a natural mouse monoclonal antibody recognizing epitopes shared by oxidized low-density lipoprotein and chaperonin 60 of Aggregatibacter actinomycetemcomitans
- 2016
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Ingår i: Immunologic research. - : Humana Press. - 0257-277X .- 1559-0755. ; 64:3, s. 699-710
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Tidskriftsartikel (refereegranskat)abstract
- Natural antibodies are predominantly antibodies of the IgM isotype present in the circulation of all vertebrates that have not been previously exposed to exogenous antigens. They are often directed against highly conserved epitopes and bind to ligands of varying chemical composition with low affinity. In this study we cloned and characterized a natural mouse monoclonal IgM antibody selected by binding to malondialdehyde acetaldehyde epitopes on low-density lipoprotein (LDL). Interestingly, the IgM antibody cross-reacted with Aggregatibacter actinomycetemcomitans (Aa) bacteria, a key pathogenic microbe in periodontitis reported to be associated with risk factor for atherosclerosis, thus being named as Aa_Mab. It is more intriguing that the binding molecule of Aa to Aa_Mab IgM was found to be Aa chaperonin 60 or HSP60, a member of heat-shock protein family, behaving not only as a chaperone for correct protein folding but also as a powerful virulence factor of the bacteria for inducing bone resorption and as a putative pathogenic factor in atherosclerosis. The findings will highlight the question of whether molecular mimicry between pathogen components and oxidized LDL could lead to atheroprotective immune activity, and also would be of great importance in potential application of immune response-based preventive and therapeutic strategies against atherosclerosis and periodontal disease.
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