Effects of TNF-α blocking on experimental periodontitis and type 2 diabetes in obese diabetic Zucker rats

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

J Clin Periodontol. 2015 Sep;42(9):807-16. doi: 10.1111/jcpe.12442. Epub 2015 Sep 28.


Tumour necrosis factor α (TNF-α) is considered a key signalling modulator in the pathogenesis of both periodontitis (PD) and type 2 diabetes mellitus (DM2). This study aims at elucidating the effect of TNF-α blocking on the interplay between PD and DM2.


Obese diabetic Zucker rats and their lean littermates were divided into five treatment groups with or without periodontitis. Anti-TNF-α treatment was provided with Etanercept injections. Diabetic state was evaluated by oral glucose tolerance test, the homeostatic model assessment, free fatty acids and blood glucose. Systemic inflammation was assessed by measurement of interleukin (IL)-1β, IL-6 and TNF-α in plasma. Kidney complications were evaluated by real-time rtPCR, creatinine clearance rate, urinary albumin excretion and increase in weight. PD was evaluated by registration of alveolar bone level.


After 4 weeks the diabetic state was modified by Etanercept treatment with lower insulin levels and lower homeostatic model assessment. Furthermore, while kidney complications were reduced by Etanercept treatment, PD had no effect. PD was influenced by diabetic state, but the impact was attenuated by Etanercept treatment.


In this study anti-TNF-α treatment improved glucose tolerance and compensated for the increased periodontal disease in obese diabetic Zucker. PD did not influence diabetic parameters assessed including complications of the rats kidneys.

© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Salivary bacterial fingerprints of established oral disease revealed by the Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS) technique.

Belstrøm D1, Paster BJ2,3, Fiehn NE4, Bardow A5, Holmstrup P6.



The composition of the salivary microbiota, as determined using various molecular methods, has been reported to differentiate oral health from diseases. Thus, the purpose of this study was to utilize the newly developed molecular technique HOMINGS (Human Oral Microbe Identification using Next Generation Sequencing) for comparison of the salivary microbiota in patients with periodontitis, patients with dental caries, and orally healthy individuals. The hypothesis was that this method could add on to the existing knowledge on salivary bacterial profiles in oral health and disease.


Stimulated saliva samples (n=30) were collected from 10 patients with untreated periodontitis, 10 patients with untreated dental caries, and 10 orally healthy individuals. Salivary microbiota was analyzed using HOMINGS and statistical analysis was performed using Kruskal-Wallis test with Benjamini-Hochberg’s correction.


From a total of 30 saliva samples, a mean number of probe targets of 205 (range 120-353) were identified, and a statistically significant higher mean number of targets was registered in samples from patients with periodontitis (mean 220, range 143-306) and dental caries (mean 221, range 165-353) as compared to orally healthy individuals (mean 174, range 120-260) (p=0.04 and p=0.04). Nine probe targets were identified with a different relative abundance between groups (p<0.05).


Cross-sectional comparison of salivary bacterial profiles by means of HOMINGS analysis showed that different salivary bacterial profiles were associated with oral health and disease. Future large-scale prospective studies are needed to evaluate if saliva-based screening for disease-associated oral bacterial profiles may be used for identification of patients at risk of acquiring periodontitis and dental caries.

J Oral Microbiol. 2016 Jan 14;8:30170. doi: 10.3402/jom.v8.30170. eCollection 2016.

Kilde: http://www.ncbi.nlm.nih.gov/pubmed/26782357

Temporal Stability of the Salivary Microbiota in Oral Health.

Belstrøm D1, Holmstrup P1, Bardow A2, Kokaras A3, Fiehn NE4, Paster BJ3,5.



Saliva is a biological fluid suitable for biomarker analysis, and differences in the salivary microbiota in oral health and disease have been reported. For such comparative analyses, time of sampling is critical since the bacterial composition may vary throughout the day, i.e., diurnal variation. The purpose of this study is to compare the salivary microbiome over time to determine the optimal time for sampling.


Stimulated saliva samples were collected from 5 orally healthy individuals in 4 h intervals for 24 h, and collection was repeated 7 days later (number of samples per person, n = 12, total number of samples, n = 60). Salivary microbiota was analyzed using the Human Oral Microbe Identification using Next Generation Sequencing (HOMINGS), and statistical analysis was performed using the Kruskal-Wallis test with Benjamini-Hochberg’s correction for multiple comparisons, cluster analysis, principal component analysis and correspondence analysis.


From a total of 60 saliva samples, 477 probe targets were collectively identified with a mean number of probes per sample of 207 (range: 153-307). Little or no variation in microbial profiles within subjects was observed over time.


Although there was considerable variation between subjects, microbial profiles within subjects were stable throughout a 24 hour period and after 1 week. Since there is little or no evidence of diurnal variation of the salivary microbiome, time of sampling of saliva is not critical for perturbation or other microbial studies.

PLoS One. 2016 Jan 22;11(1):e0147472. doi: 10.1371/journal.pone.0147472. eCollection 2016.

Kilde: http://www.ncbi.nlm.nih.gov/pubmed/26799067

Bacterial composition in whole saliva from patients with severe hyposalivation- a case-control study.

Belstrøm D1, Holmstrup P1, Fiehn NE2, Rosing K1, Bardow A3, Paster BJ4,5, Lynge Pedersen AM3.



The purpose of this study was to compare the microbiota of stimulated whole saliva samples from patients with severe hyposalivation to samples from individuals with normal whole saliva flow rates. It was hypothesized that the two groups differ with regard to salivary bacterial profiles.


This cross-sectional study included 36 participants (24 females and 12 males, mean age 58.5 years) with severe hyposalivation and 36 gender-, age- and geographically-matched participants with normal salivary secretion from the Danish Health Examination Survey (DANHES). The microbiota of stimulated whole saliva samples was characterized by HOMINGS.


The two groups had comparable caries experience measured by decayed-missed-filled-surfaces/-teeth and decayed-missed-filled-root surfaces as well as active caries lesions. In addition, no single probe-target was present with a significant difference in frequency or proportional presence between groups. Furthermore, data reduction by principal component analysis and correspondence analysis showed comparable bacterial community profiles between groups.


The results indicate that the salivary bacterial profiles of patients with severe hyposalivation do not differ from those of individuals with normal salivary secretion, when there are virtually no untreated active caries lesions present in the oral cavity. This article is protected by copyright. All rights reserved.

This article is protected by copyright. All rights reserved.

Oral Dis. 2016 Jan 29. doi: 10.1111/odi.12452. [Epub ahead of print]

Kilde: http://www.ncbi.nlm.nih.gov/pubmed/26824889

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

Holm NR1, Belstrøm D1, Østergaard JA2,3, Schou S4, Holmstrup P1, Bay Grauballe MC1.



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.


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.


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.


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.

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

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

Ny lærerbog i parodontologi – Clinical Periodontology and Implant Dentistry, 2 Volume Set. 6th Edition

Bogen kan købes i bogladen på Panum Instituttet eller bestilles over nettet via nedenstående link.


Now in its sixth edition, Clinical Periodontology and Implant Dentistry is the must-have resource for practitioners specialising in periodontal care and implant dentistry. The chapters have been extensively revised with 40% of the content new to this edition. Maintaining the widely praised two-volume format introduced in the previous edition, the editorial team has once again brought together the world s top international specialists to share their expertise on all aspects of periodontology, periodontal health and the use of implants in the rehabilitation of the periodontally compromised patient. Seamlessly integrating foundational science, practical clinical protocols, and recent advances in the field, Clinical Periodontology and Implant Dentistry, Sixth Edition enhances its stellar reputation as the cornerstone reference work on periodontology.

For more information please click on:


Title Index:


Part 1: Anatomy

Part 2: Epidemiology

Part 3: Microbiology

Part 4: Host Parasite Interactions

Part 5: Influence of Occlusion

Part 6: Periodontal Pathology

Part 7: Peri-implant Pathology

Part 8: Tissue Regeneration


Part 9: Examination Protocols

Part 10: Treatment Planning Protocols

Part 11: Initial Periodontal Therapy (Infection Control)

Part 12: Additional Therapy

Part 13: Reconstructive Therapy

Part 14: Surgery for Implant Installation

Part 15: Reconstructive Ridge Therapy

Part 16: Occlusal and Prosthetic Therapy

Part 17: Orthodontics and Periodontics

Part 18: Supportive Care


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The complement system and its role in the pathogenesis of periodontitis: current concepts.


Periodontitis is a highly prevalent inflammatory disease in tooth supporting tissues, induced by bacteria growing in a biofilm on tooth surfaces. Components of the complement system are present in the periodontal tissue and the system is activated in periodontitis. Continuous complement activation and modulation by bacteria within the biofilm in periodontal pockets, however, may enhance local tissue destruction, providing the biofilm with both essential nutrients and space to grow.
A more profound understanding of the mechanisms involved in complement-derived tissue degradation may facilitate the development of new treatment concepts for periodontitis. Further studies on the role of complement in periodontitis pathogenesis may also contribute to the understanding of why some individuals fail to resolve periodontitis. Here, we review evidence that links complement to the pathogenesis of periodontitis with an emphasis on interaction of complement with bacteria from periodontitis-associated biofilm.

© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Kilde: http://www.ncbi.nlm.nih.gov/pubmed/25040158


Viable bacteria associated with red blood cells and plasma in freshly drawn blood donations.



Infection remains a leading cause of post-transfusion mortality and morbidity. Bacterial contamination is, however, detected in less than 0.1% of blood units tested. The aim of the study was to identify viable bacteria in standard blood-pack units, with particular focus on bacteria from the oral cavity, and to determine the distribution of bacteria revealed in plasma and in the red blood cell (RBC)-fraction.


Cross-sectional study. Blood were separated into plasma and RBC-suspensions, which were incubated anaerobically or aerobically for 7 days on trypticase soy blood agar (TSA) or blue lactose plates. For identification colony PCR was performed using primers targeting 16S rDNA.


Blood donors attending Capital Region Blood Bank, Copenhagen University Hospital, Rigshospitalet, Hvidovre, Denmark, October 29th to December 10th 2013.


60 donors (≥50 years old), self-reported medically healthy.


Bacterial growth was observed on plates inoculated with plasma or RBCs from 62% of the blood donations. Growth was evident in 21 (35%) of 60 RBC-fractions and in 32 (53%) of 60 plasma-fractions versus 8 of 60 negative controls (p = 0.005 and p = 2.6×10-6, respectively). Propionibacterium acnes was found in 23% of the donations, and Staphylococcus epidermidis in 38%. The majority of bacteria identified in the present study were either facultative anaerobic (59.5%) or anaerobic (27.8%) species, which are not likely to be detected during current routine screening.


Viable bacteria are present in blood from donors self-reported as medically healthy, indicating that conventional test systems employed by blood banks insufficiently detect bacteria in plasma. Further investigation is needed to determine whether routine testing for anaerobic bacteria and testing of RBC-fractions for adherent bacteria should be recommended.


Kilde: http://www.ncbi.nlm.nih.gov/pubmed/25751254

Differentiation of salivary bacterial profiles of subjects with periodontitis and dental caries.


Bacterial profiles of saliva in subjects with periodontitis and dental caries have been demonstrated to differ from that of oral health. The aim of this comparative analysis of existing data generated by the Human Oral Microbe Identification Microarray (HOMIM) from 293 stimulated saliva samples was to compare bacterial profiles of saliva in subjects with periodontitis and dental caries.

Kilde: http://www.ncbi.nlm.nih.gov/pubmed/25854857