Presence and consequence of tooth periapical radiolucency in patients with cirrhosis.

Hepat Med. 2016 Sep 13;8:97-103. eCollection 2016.

Abstract

BACKGROUND:

Periapical radiolucency is the radiographic sign of inflammatory bone lesions around the apex of the tooth. We determined the prevalence and predictors of periapical radiolucency in patients with cirrhosis and the association with systemic inflammation status and cirrhosis-related complications.

METHODS:

A total of 110 cirrhosis patients were consecutively enrolled. Periapical radiolucency was defined as the presence of radiolucency or widening of the periapical periodontal ligament space to more than twice the normal width. Predictors of periapical radiolucency and the association with systemic inflammation markers and cirrhosis-related complications were explored by univariable and multivariable logistic regression analyses.

RESULTS:

Periapical radiolucency was present in one or more teeth in 46% of the patients. Strong predictors were gross caries (odds ratio [OR] 3.12, 95% confidence interval [CI] 1.43-6.79) and severe periodontitis (OR 3.98, 95% CI 1.04-15.20). Also old age (OR 1.10, 95% CI 1.01-1.19) and smoking (OR 3.24, 95% CI 1.02-17.62) were predictors. However, cirrhosis etiology (alcoholic vs nonalcoholic) or severity (Model of End-Stage Liver Disease score) were not predictors. The patients with periapical radiolucency had higher C-reactive protein (15.8 mg/L vs 8.1 mg/L, P=0.02) and lower albumin contents (25 g/L vs 28 g/L, P=0.04) than those without. Furthermore, the patients with periapical radiolucency had a higher prevalence of cirrhosis-related complications such as ascites, hepatic encephalopathy, and/or variceal bleeding (46% vs 27%, P=0.05).

CONCLUSION:

Periapical radiolucency is often present as an element of poor oral health status and likely has an adverse clinical significance, which should motivate diagnostic and clinical attention to the findings.

https://www.ncbi.nlm.nih.gov/pubmed/27695370

Kilde: Pubmed.com

Pseudomonas aeruginosa Microcolonies in Coronary Thrombi from Patients with ST-Segment Elevation Myocardial Infarction.

PLoS One. 2016 Dec 28;11(12):e0168771. doi: 10.1371/journal.pone.0168771. eCollection 2016.

Abstract

Chronic infection is associated with an increased risk of atherothrombotic disease and direct bacterial infection of arteries has been suggested to contribute to the development of unstable atherosclerotic plaques. In this study, we examined coronary thrombi obtained in vivo from patients with ST-segment elevation myocardial infarction (STEMI) for the presence of bacterial DNA and bacteria. Aspirated coronary thrombi from 22 patients with STEMI were collected during primary percutaneous coronary intervention and arterial blood control samples were drawn from radial or femoral artery sheaths. Analyses were performed using 16S polymerase chain reaction and with next-generation sequencing to determine bacterial taxonomic classification. In selected thrombi with the highest relative abundance of Pseudomonas aeruginosa DNA, peptide nucleic acid fluorescence in situ hybridization (PNA-FISH) with universal and species specific probes was performed to visualize bacteria within thrombi. From the taxonomic analysis we identified a total of 55 different bacterial species. DNA from Pseudomonas aeruginosa represented the only species that was significantly associated with either thrombi or blood and was >30 times more abundant in thrombi than in arterial blood (p<0.0001). Whole and intact bacteria present as biofilm microcolonies were detected in selected thrombi using universal and P. aeruginosa-specific PNA-FISH probes. P. aeruginosa and vascular biofilm infection in culprit lesions may play a role in STEMI, but causal relationships remain to be determined.

https://www.ncbi.nlm.nih.gov/pubmed/28030624

Kilde: Pubmed.com

Metaproteomics of saliva identifies human protein markers specific for individuals with periodontitis and dental caries compared to orally healthy controls.

Metaproteomics of saliva identifies human protein markers specific for individuals with periodontitis and dental caries compared to orally healthy controls.

Belstrøm D1Jersie-Christensen RR2Lyon D3Damgaard C4Jensen LJ3Holmstrup P1Olsen JV2.

 Abstract

BACKGROUND:

The composition of the salivary microbiota has been reported to differentiate between patients with periodontitis, dental caries and orally healthy individuals. To identify characteristics of diseased and healthy saliva we thus wanted to compare saliva metaproteomes from patients with periodontitis and dental caries to healthy individuals.

METHODS:

Stimulated saliva samples were collected from 10 patients with periodontitis, 10 patients with dental caries and 10 orally healthy individuals. The proteins in the saliva samples were subjected to denaturing buffer and digested enzymatically with LysC and trypsin. The resulting peptide mixtures were cleaned up by solid-phase extraction and separated online with 2 h gradients by nano-scale C18 reversed-phase chromatography connected to a mass spectrometer through an electrospray source. The eluting peptides were analyzed on a tandem mass spectrometer operated in data-dependent acquisition mode.

RESULTS:

We identified a total of 35,664 unique peptides from 4,161 different proteins, of which 1,946 and 2,090 were of bacterial and human origin, respectively. The human protein profiles displayed significant overexpression of the complement system and inflammatory markers in periodontitis and dental caries compared to healthy controls. Bacterial proteome profiles and functional annotation were very similar in health and disease.

CONCLUSIONS:

Overexpression of proteins related to the complement system and inflammation seems to correlate with oral disease status. Similar bacterial proteomes in healthy and diseased individuals suggests that the salivary microbiota predominantly thrives in a planktonic state expressing no disease-associated characteristics of metabolic activity.

PeerJ. 2016 Sep 14;4:e2433. doi: 10.7717/peerj.2433. eCollection 2016.

Link til artiklen: https://www.ncbi.nlm.nih.gov/pubmed/27672500

In vitro complement activation, adherence to red blood cells and induction of mononuclear cell cytokine production by four strains of Aggregatibacter actinomycetemcomitans with different fimbriation and expression of leukotoxin.

In vitro complement activation, adherence to red blood cells and induction of mononuclear cell cytokine production by four strains of Aggregatibacter actinomycetemcomitans with different fimbriation and expression of leukotoxin.

Damgaard C1,2Reinholdt J3Palarasah Y4Enevold C5,6Nielsen C7Brimnes MK6Holmstrup P5Nielsen CH5,6.

Abstract

BACKGROUND AND OBJECTIVE:

The periodontal pathogen Aggregatibacter actinomycetemcomitans has been proposed as pro-atherogenic, and complement-mediated adherence to red blood cells (RBCs) may facilitate its systemic spread. We investigated the ability of four strains of A. actinomycetemcomitans with differential expression of leukotoxin A (LtxA) and fimbriae to activate complement, adhere to RBCs and elicit cytokine responses by mononuclear cells (MNCs).

MATERIAL AND METHODS:

Aggregatibacter actinomycetemcomitans serotype b strains HK 921, HK 1651, HK 2092 and HK 2108 were fluorescence-labeled, incubated with human whole blood cells in the presence of autologous serum, and assessed for RBC adherence by flow cytometry and for capacity to induce cytokine production by cytometric bead array analysis. The levels of IgG to A. actinomycetemcomitans serotype b were quantified by ELISA, as was consumption of complement.

RESULTS:

The JP2 clone variants HK 1651 and, to a lesser extent, HK 2092, consumed complement efficiently, while HK 2108 (= strain Y4) consumed complement poorly. Nonetheless, the four tested strains adhered equally well to RBCs in the presence of autologous serum, without causing RBC lysis. The JP2 clone variant HK 2092, selectively lacking LtxA production, induced higher production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-10 by MNCs than did the other three strains, while the four strains induced similar production of IL-12p70. RBCs facilitated the HK 2092-induced production of TNF-α and IL-1β, and IL-6 was enhanced by RBCs, and this facilitation could be counteracted by blockade of complement receptor 3 (CD11b/CD18).

CONCLUSION:

Our data suggest that the JP2 clone of A. actinomycetemcomitans, most closely resembled by the variant HK 1651, activates complement well, while strain Y4, represented by HK 2108, activates complement poorly. However, all strains of A. actinomycetemcomitans adhere to RBCs and, when capable of producing LtxA, prevent production of inflammatory cytokines by MNCs. This “immunologically silent” immune adherence may facilitate systemic spread and atherogenesis.

© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

J Periodontal Res. 2016 Sep 24. doi: 10.1111/jre.12414. [Epub ahead of print]

Link til artiklen: https://www.ncbi.nlm.nih.gov/pubmed/27663487

 

Relation of Periodontitis to Risk of Cardiovascular and All-Cause Mortality (from a Danish Nationwide Cohort Study).

Relation of Periodontitis to Risk of Cardiovascular and All-Cause Mortality (from a Danish Nationwide Cohort Study).

Hansen GM1Egeberg A2Holmstrup P3Hansen PR4.

 Abstract

Periodontitis and atherosclerosis are highly prevalent chronic inflammatory diseases, and it has been suggested that periodontitis is an independent risk factor of cardiovascular disease (CVD) and that a causal link may exist between the 2 diseases. Using Danish national registers, we identified a nationwide cohort of 17,691 patients who received a hospital diagnosis of periodontitis within a 15-year period and matched them with 83,003 controls from the general population. We performed Poisson regression analysis to determine crude and adjusted incidence rate ratios of myocardial infarction, ischemic stroke, cardiovascular death, major adverse cardiovascular events, and all-cause mortality. The results showed that patients with periodontitis were at higher risk of all examined end points. The findings remained significant after adjustment for increased baseline co-morbidity in periodontitis patients compared with controls, for example, with adjusted incidence rate ratio 2.02 (95% CI 1.87 to 2.18) for cardiovascular death and 2.70 (95% CI 2.60 to 2.81) for all-cause mortality. Patients with a hospital diagnosis of periodontitis have a high burden of co-morbidity and an increased risk of CVD and all-cause mortality. In conclusion, our results support that periodontitis may be an independent risk factor for CVD.

Copyright © 2016 Elsevier Inc. All rights reserved.

Am J Cardiol. 2016 Aug 15;118(4):489-93. doi: 10.1016/j.amjcard.2016.05.036. Epub 2016 May 30.

Link til artiklen: https://www.ncbi.nlm.nih.gov/pubmed/27372888

Porphyromonas gingivalis-induced production of reactive oxygen species, tumor necrosis factor-α, interleukin-6, CXCL8 and CCL2 by neutrophils from localized aggressive periodontitis and healthy donors: modulating actions of red blood cells and resolvin E1.

Porphyromonas gingivalis-induced production of reactive oxygen species, tumor necrosis factor-α, interleukin-6, CXCL8 and CCL2 by neutrophils from localized aggressive periodontitis and healthy donors: modulating actions of red blood cells and resolvin E1.

Damgaard C1,2,3Kantarci A3Holmstrup P1Hasturk H3Nielsen CH1,2Van Dyke TE3.

 

Abstract

BACKGROUND AND OBJECTIVES:

Porphyromonas gingivalis is regarded as a significant contributor in the pathogenesis of periodontitis and certain systemic diseases, including atherosclerosis. P. gingivalis occasionally translocates from periodontal pockets into the circulation, where it adheres to red blood cells (RBCs). This may protect the bacterium from contact with circulating phagocytes without affecting its viability.

MATERIAL AND METHODS:

In this in vitro study, we investigated whether human peripheral blood neutrophils from 10 subjects with localized aggressive periodontitis (LAgP) and 10 healthy controls release the proinflammatory cytokines interleukin (IL)-6, tumor necrosis factor α (TNF-α), the chemokine (C-X-C motif) ligand 8 (CXCL8; also known as IL-8) and chemokine (C-C motif) ligand 2 (CCL2; also known as monocyte chemotactic protein-1) and intracellular reactive oxygen species (ROS) in response to challenge with P. gingivalis. In addition, the impact of RBC interaction with P. gingivalis was investigated. The actions of resolvin E1 (RvE1), a known regulator of P. gingivalis induced neutrophil responses, on the cytokine and ROS responses elicited by P. gingivalis in cultures of neutrophils were investigated.

RESULTS:

Upon stimulation with P. gingivalis, neutrophils from subjects with LAgP and healthy controls released similar quantities of IL-6, TNF-α, CXCL8, CCL2 and intracellular ROS. The presence of RBCs amplified the release of IL-6, TNF-α and CCL2 statistically significant in both groups, but reduced the generation of ROS in the group of healthy controls, and showed a similar tendency in the group of subjects with LAgP. RvE1 had no impact on the production of intracellular ROS, TNF-α, IL-6, CXCL8 and CCL2 by neutrophils from either group, but tended to reduce the generation of ROS in subjects with LAgP in the absence of RBCs.

CONCLUSIONS:

Our data support that binding to RBCs protects P. gingivalis from ROS and concomitantly enhances neutrophil release of proinflammatory cytokines providing a selective advantage for P. gingivalis growth.

© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

J Periodontal Res. 2016 May 5. doi: 10.1111/jre.12388. [Epub ahead of print]

Link til artiklen: https://www.ncbi.nlm.nih.gov/pubmed/27146665

Blockade of RAGE in Zucker obese rats with experimental periodontitis

Grauballe MB, Østergaard JA, Schou S, Flyvbjerg A, Holmstrup P

J Periodontal Res. 2016 Mar 12. doi: 10.1111/jre.12373. [Epub ahead of print]

BACKGROUND AND OBJECTIVE:

Periodontitis and type 2 diabetes mellitus (T2D) are two interrelated chronic diseases. Periodontitis is more prevalent in patients with T2D than in healthy subjects, and studies indicate that periodontitis impacts the metabolic control of patients with T2D. Hyperglycemia in T2D leads to the formation of advanced glycation end-products (AGEs). Binding of AGEs to the receptor of AGE (RAGE) elicits an increased inflammatory response that may be a key modulator linking the two diseases. The present study aimed to elucidate the effect of blocking the RAGE on the interrelationship between periodontitis and T2D in a rat model of both diseases.

MATERIAL AND METHODS:

Zucker obese rats (HsdHlr:ZUCKER-Lepr fa/fa ) and their lean littermates were divided into five treatment groups, with and without periodontitis. Monoclonal anti-RAGE IgG3 were injected into the rats three times a week. The diabetic state was evaluated by oral glucose tolerance tests (OGTTs), the homeostasis model assessment (HOMA), concentration of free fatty acids and repeated measurements of blood glucose. Markers of systemic inflammation, including interleukin (IL)-1β, IL-6 and tumor necrosis factor α, were evaluated in plasma. Kidney complications were evaluated by quantitative real-time PCR, the creatinine clearance rate, the albumin excretion rate and kidney hypertrophy. Periodontitis was evaluated by morphometric registration of alveolar bone loss and radiographic recording of bone support.

RESULTS:

The diabetic state was improved by antibody treatment for 4 wk, resulting in a lower area under the glucose concentration curve during OGTTs, lower insulin levels and a lower HOMA. Furthermore, the antibody treatment resulted in milder kidney complications, as evaluated by measuring the albumin excretion rate and the kidney weight. There was no impact of periodontal inflammation on the level of complications. Periodontal bone support was influenced by diabetes, but the altered diabetic status as a result of treatment with anti-RAGE Ig had no effect on periodontitis.

CONCLUSION:

In this study, treatment with anti-RAGE IgG3 resulted in improved glucose tolerance and attenuated renal complications. However, no effect was observed on the diabetes-associated periodontitis in Zucker obese rats. Furthermore, periodontitis had no effect on diabetic markers or renal complications. Therefore, activation of RAGE is important in the development of T2D.

© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

http://www.ncbi.nlm.nih.gov/pubmed/26971526

Detection of Undiagnosed Diabetes in the Dental Setting

Daniel Beltrøm, Morten Bay Grauball, Niels-Christian Reimers Holm, Allan FlyvbjergPalle Holmstrup

Current Oral Health Reports , Volume 3, Issue 1, pp 1-6

Diabetes and periodontitis are multifactorial chronic inflammatory diseases affecting hundreds of millions individuals worldwide. There is a bidirectional relationship between the two diseases, as diabetes is associated with increased prevalence, severity, and progression of periodontitis, and untreated periodontitis is associated with poorer metabolic control in individuals with diabetes. Furthermore, treatment of periodontitis has been shown to improve the metabolic status in patients with diabetes. Therefore, successful prevention and treatment of patients with diabetes and periodontitis requires an interdisciplinary approach involving both dentists and physicians. It has recently been demonstrated that periodontal disease status can be used as a predictor for diabetes and prediabetes risk assessment, and several investigations have reported that chair-side measurement of glycated hemoglobin levels (HbA1C), performed in the dental setting, can help in identifying individuals with potentially undiagnosed diabetes and prediabetes. Thus, since a significant part of the adult population attends the dental office more regularly than their physician, the dental office seems an intriguing venue for screening and prevention of diabetes. In the future chair-side measurements of HbA1C levels in combination with periodontal examination may therefore be performed as a routine in the dental setting. Such an approach might potentially facilitate early identification of individuals with prediabetes and undiagnosed, asymptomatic diabetes and accordingly referred to their general physician for further diagnosis, prevention, and treatment at early stages of disease, thereby reducing potential diabetic complications.

http://link.springer.com/article/10.1007/s40496-016-0077-z

 

Identification of Individuals With Undiagnosed Diabetes and Pre-Diabetes in a Danish Cohort Attending Dental Treatment

Holm NR, Belstrøm D, Østergaard JA, Schou S, Holmstrup P, Bay Grauballe MC

J Periodontol. 2016 Jan 8:1-12. [Epub ahead of print]

BACKGROUND AND OBJECTIVE:

It is estimated that 3.6% and 13.6% of the Danish population suffer from undiagnosed type 2 diabetes and pre-diabetes, respectively. Periodontitis is an established complication to diabetes. Identification of individuals with diabetes and pre-diabetes is important to reduce diabetes-related complications including periodontitis. The objective of the study was to identify individuals with undiagnosed diabetes or pre-diabetes among individuals attending a dental setting for diagnosis and treatment.

METHODS:

291 adults with no history of diabetes were included in the study (periodontitis patients n=245, non-periodontitis control individuals n=46). Participants answered questionnaires concerning general health, including family history of diabetes. BMI, waist circumference, fat percentage, and glycated hemoglobin level (HbA1c) were recorded chair-side. Periodontal examination was performed and radiographic bone level measured. All individuals were informed about the HbA1c result, and referred to their physician if HbA1c levels were above those of the American Diabetes Association guidelines.

RESULTS:

A total of 9 (3.1%) and 79 (27.1%) subjects were identified with HbA1c levels corresponding to guideline values for diabetes and pre-diabetes respectively. Higher proportions of patients with undiagnosed diabetes and pre-diabetes were observed in the periodontitis group (32.7%) than in the control group (17.4%) (p=0.054). Identification of diabetes and pre-diabetes based on a diagnosis of periodontitis yielded a sensitivity of 0.91 and specificity of 0.19.

CONCLUSION:

This study confirms that individuals with undiagnosed diabetes and pre-diabetes can be identified in the dental office by chair-side HbA1c recordings. Routine measurement of HbA1c in dental offices, eventually restricted to risk subjects, may help identification of individuals with diabetes and pre-diabetes at early stages of disease, which may prevent future complications.

http://www.ncbi.nlm.nih.gov/pubmed/26745612