U. van der Velden

Effect of a chlorhexidine mouthrinse on plaque, gingival inflammation and staining in gingivitis patients: a systematic review

AIM To systematically evaluate the efficacy of chlorhexidine (CHX) mouthrinses on plaque, gingival inflammation and staining in gingivitis patients. MATERIAL & METHODS Medline, EMBASE and Cochrane Central Register of Controlled Trials were searched through April 2011. Randomized controlled clinical trials comparing CHX to placebo/control mouthrinses or oral hygiene (OH) ≥ 4 weeks were included. RESULTS Among 1355 titles, 30 publications fulfilled the selection criteria. Meta-analysis (MA) showed significant weighted mean differences (WMD) favouring CHX. This was -0.39 [95% CI: -0.70; -0.08] for the Plaque Index Silness & Löe, -0.67 [95% CI: -0.82; -0.52] for the Plaque-Index Quigley & Hein (PIQH), -0.32 [95% CI: -0.42; -0.23] for the Gingival Index (GI), -0.08 [95% CI: -0.10; -0.05] for the bleeding aspect of the GI, -0.21 [95% CI: -0.37; -0.04] for the Papillary BIeeding Index, -0.16 [95% CI: -0.26; -0.07] for Bleeding on Marginal Probing and 0.91 [95% CI: 0.12;1.70] for the Lobene Stain Index. MA of studies with a low risk of author-estimated bias showed a WMD of -0.68 [95% CI: -0.85; -0.51] for the PIQH and -0.24 [95% CI: -0.29; -0.20] for the GI in favour of CHX. Relative to control, the reduction with CHX for plaque was 33% and for gingivitis 26%. CHX rinsing groups demonstrated significantly more staining. CONCLUSIONS In gingivitis patients, CHX mouthrinses together with OH versus placebo- or control mouthrinse provide significant reductions in plaque and gingivitis scores, but a significant increase in staining score.

Micronutritional approaches to periodontal therapy

AIM Periodontitis results from the loss of a delicate balance between microbial virulence factors and a proportionate host response. Nutritional factors have been implicated in several chronic inflammatory diseases that are associated with periodontitis. This manuscript reviews the evidence for nutritional exposures in the etiology and therapeutic management of periodontitis, and makes recommendations for daily nutritional intake for vitamin C (ascorbic acid), vitamin D, calcium, and antioxidants. RESULTS AND CONCLUSION Periodontitis is associated with low serum/plasma micronutrient levels, which may result from dietary and/or life-style factors as well as nutrigenetic characteristics. Early evidence suggests beneficial outcomes from nutritional interventions; supporting the contention that daily intake of certain nutrients should be at the higher end of recommended daily allowances. For prevention and treatment of periodontitis daily nutrition should include sufficient antioxidants, vitamin D, and calcium. Inadequate antioxidant levels may be managed by higher intake of vegetables, berries, and fruits (e.g. kiwi fruit), or by phytonutrient supplementation. Current evidence is insufficient to support recommendations of mono-antioxidant vitamin supplements and randomised controlled double-blind intervention studies are needed to provide evidence to underpin future recommendations. Inadequate supply of vitamin D and calcium may be addressed by implementing changes in diet/life style or by supplements.

Cystatins S and C in Human Whole Saliva and in Glandular Salivas in Periodontal Health and Disease

Cystatins are inhibitors of cysteine proteinases and could play a protective and regulatory role under inflammatory conditions. Since total cystatin activity of whole saliva was increased in periodontal patients (Henskens et al., 1993), we wanted to investigate the types or origins of cystatins involved in this increase. Distinct types of cystatins were identified by isoelectric focusing and immunoblotting with specific antibodies against one of the salivary acidic isoforms, cystatin S, and the widely distributed basic cystatin C. Clarified human whole saliva (CHWS) of healthy subjects contained cystatin S, whereas cystatin C was barely detectable. In contrast, in CHWS of gingivitis and periodontitis patients, both cystatin C and S levels were higher. The origin of cystatin activity was investigated by collecting submandibular (SM), sublingual (SL), and parotid (PAR) saliva from seven subjects with mild gingivitis. Total cystatin activity was about five times higher in SM saliva than in PAR saliva. In SM and SL saliva, both cystatins S and C were demonstrated. In contrast, in PAR samples, solely cystatin C was detectable. The introduction of experimental gingivitis in one periodontally healthy subject resulted in the appearance of a cystatin C band in PAR saliva and in an increase of cystatins S and C in SM saliva. We conclude that the previously observed increase of cystatin activity in whole saliva in inflammatory periodontal disease is, at least in part, due to an increased glandular output of both the isof orm cystatin S (pI 4.7) and the basic cystatin C (pI 9.0).

A type 2 response in lipopolysaccharide (LPS)-stimulated whole blood cell cultures from periodontitis patients

It is acknowledged that periodontitis results from the interaction of the host immune response with bacteria accumulating on the tooth surfaces. Although bacteria are essential, they are insufficient to cause the disease. Despite this knowledge it remains unclear why certain individuals are more susceptible to periodontitis than others. Therefore the present study investigated whether differences exist in the actual immune response between periodontitis patients and controls after stimulation of peripheral blood cells. Whole blood cell cultures (WBCC) were stimulated with LPS from Escherichia coli during 18 h and the release of prostaglandin E2 (PGE2), IL‐1β, IL‐6, IL‐8, IL‐10, IL‐12p40, IL‐12p70 and tumour necrosis factor‐alpha (TNF‐α) was measured. The levels of PGE2 were two‐fold higher in the WBCC from periodontitis patients than from controls. In contrast, the levels of IL‐12p70 in WBCC from patients were two‐fold lower. Furthermore, WBCC from patients secreted lower levels of IL‐1β and higher levels of IL‐8 when compared with WBCC from controls. No differences were observed with respect to IL‐6, IL‐10, IL‐12p40 and TNF‐α production. It is known from the literature that LPS‐stimulated WBCC reflect specifically the behaviour of the monocytes and that monocytes are peripheral precursors of antigen‐presenting cells (APC). Therefore it is concluded that the monocytes in the present WBCC from periodontitis patients are responsible for the higher levels of PGE2 and lower levels of IL‐12p70. Since it is has been shown that APC‐derived IL‐12p70 induces type (Th1) cells that promote cellular immunity, while APC‐derived PGE2 induces type 2‐helper (Th2) cells that promote humoral immunity, it is postulated that APC from periodontitis patients may have a bias in directing Th2 responses and thereby promoting the humoral immunity in periodontitis.

Clinical and microbiological effects of initial periodontal therapy in conjunction with amoxicillin and clavulanic acid in patients with adult periodontitis

The aim of the present study was to investigate the clinical and microbiological effects of initial periodontal therapy in conjunction with systemic amoxicillin plus clavulanic acid in adult periodontitis patients using a double-blind, parallel-group, and placebo-controlled protocol. 21 patients with a clinical diagnosis of generalised adult periodontitis were recruited. Clinical measurements and microbiological assessments were carried out at baseline, 3, and 12 months post-treatment. Approximately 6 weeks after initial periodontal treatment (3-6 h), patients were randomly assigned to receive coded study medication of 500 mg amoxicillin plus 125 mg clavulanic acid (Augmentin) or placebo, every 8 h for 10 days. Patients returned for follow-up visits 3, 6, 9, and 12 months after completion of the medication. The mean plaque index (PI) at baseline was 1.1 for placebo group and 0.9 for the test group. At 3 months, the PI had dropped to 0.3 in both groups, and was maintained during the rest of the study. The changes in bleeding on probing (BOP) and gingival index (GI) in the course of the study were similar in both groups. The mean whole mouth probing pocket depth (PPD) in the placebo group was 3.8 mm at baseline and 3.9 mm in the test group. A mean reduction of 1.0 mm in the placebo group and 0.9 mm in the test group was observed during the first 3 months. No further reduction in PPD was noticed during the study period in either group. There was no statistically significant difference in the PPD reduction between the 2 groups. The change in clinical attachment level (CAL) from baseline to 3 months amounted to 0.5 mm in both groups. Between 3 and 12 months, the CAL changed in neither group. In both groups, treatment resulted in a decrease in the number of spirochetes and motile rods in positive patients, but no significant differences between either group were noted in any of the dark field microscopy observations. At baseline, 1 patient in the placebo group and 2 patients in the test group were culture positive for Actinobacillus actinomycetemcomitans (Aa). After therapy, Aa was not detectable in the placebo group and 1 patient remained positive in the test group. In the placebo group, the number of patients positive for Porphyromonas gingivalis (Pg) decreased from 7 to 2 after therapy. In the test group, the 4 patients positive for Pg at baseline remained positive after therapy. In both groups, all subjects were positive for Prevotella intermedia (Pi) and Fusobacterium nucleatum (Fn) at baseline. At 12 months, all subjects had detectable subgingival Fn. 9 out of the 11 placebo and 8 of the 10 test patients remained positive for Pi. There were no differences in detection frequency of Peptostreptococcus micros (Pm) and Bacteroides forsythus (Bf) in both groups between baseline, 3, and 12 months post-treatment. The findings demonstrated that, in comparison to placebo, systemic amoxicillin plus clavulanic acid provided no additional clinical and microbiological effects in the treatment of adult periodontitis patients.

Effects of smoking on the ex vivo cytokine production in periodontitis.

BACKGROUND AND OBJECTIVE Smoking is associated with increased severity of periodontitis. The underlying mechanisms of this phenomenon are not well understood. The purpose of the present study was to compare the monocyte-derived T cell directing (Th1/Th2) response and pro-inflammatory cytokine production in ex vivo whole blood cell cultures (WBCC) of smoking and non-smoking chronic periodontitis patients. MATERIAL AND METHODS Venous blood was collected from 29 periodontitis patients (18 non-smokers and 11 smokers) receiving supportive periodontal treatment, and diluted 10-fold for WBCC. The WBCC were stimulated for 18 h with Neisseria meningitidis lipo-oligosaccharide (LOS) or Porphyromonas gingivalis sonic extract (Pg-SE). The production of the T cell directing cytokines interleukin (IL)-12 p40 and IL-10, as well as the pro-inflammatory cytokines IL-1beta, IL-6 and IL-8, was measured in the culture supernatants. RESULTS After LOS stimulation of WBCC, smokers showed a lower IL-12 p40/IL-10 ratio than non-smokers (P < 0.05). Interleukin-1beta production was significantly lower in smokers compared with non-smokers after stimulation with either LOS or Pg-SE (P < 0.05). Interleukin-6 and IL-8 production was similar in WBCC from both smokers and non-smokers, for both LOS and Pg-SE. CONCLUSION A more pronounced Th2 response in smoking periodontitis patients may be related to increased severity of the disease.

Effect of cannabis usage on the oral environment: a review

AIM To evaluate oral environmental changes in cannabis users. MATERIAL AND METHODS The MEDLINE and Cochrane Central register of controlled trails (CENTRAL) were searched up to April 2007 to identify appropriate studies. RESULTS Independent screening of 982 titles and abstracts (MEDLINE-Pubmed) and (Cochrane) papers resulted in seven eligible publications. CONCLUSION Based on the limited data, it seems justified to conclude that with increasing prevalence of cannabis use, oral health care providers should be aware of cannabis-associated oral side effects, such as xerostemia, leukoedema and an increased prevalence and density of Candida albicans.

Elevated platelet and leukocyte response to oral bacteria in periodontitis

Summary.  Background: Periodontitis is associated with an increased risk for cardiovascular diseases (CVD), but the underlying mechanisms are poorly understood. Recently, we showed that platelets from periodontitis patients are more activated than those from controls. Objective: Given the regularly occurring bacteremic episodes in periodontitis patients, we hypothesized that platelets and/or leukocytes from periodontitis patients are more sensitive to stimulation by oral bacteria, in particular the known periodontal pathogens, than platelets from control subjects. Methods: Three‐color flow cytometry analysis was performed to quantify activation of platelets (P‐selectin, PAC‐1, CD63) and leukocytes (CD11b) in whole blood from patients with periodontitis (n = 19) and controls (n = 18), with and without stimulation by oral bacteria. Phagocytosis was assessed by using green‐fluorescent protein (GFP)‐expressing Aggregatibacter actinomycetemcomitans (Aa). Results: Neutrophils and monocytes were activated by all species of oral bacteria tested, but no differences were observed between patients and controls. In response to several species of oral bacteria, platelets from periodontitis patients showed, compared with controls, increased exposure of P‐selectin (P = 0.027) and increased formation of platelet‐monocyte complexes (P = 0.040). Platelet‐leukocyte complexes bound and/or phagocytosed more GFP‐Aa than platelet‐free leukocytes (for neutrophils and monocytes, in both patients and controls, P < 0.001). Conclusions: In periodontitis, increased platelet response to oral bacteria is paralleled by increased formation of platelet‐leukocyte complexes with elevated capacity for bacterial clearance. We speculate that activated platelets and leukocytes might contribute to increased atherothrombotic activity.

Monocyte-derived RANTES is intrinsically elevated in periodontal disease while MCP-1 levels are related to inflammation and are inversely correlated with IL-12 levels.

Bacteria colonizing tooth surfaces are essential in the induction of an inflammatory response in the periodontal tissues, but do not cause periodontitis in everyone, implicating differences in the host immune response. These possible differences were studied using lipopolysaccharide (LPS)‐stimulated whole blood cell cultures (WBCC), which revealed a down regulation of monocyte derived interleukin‐12 (IL‐12p70) in untreated periodontitis patients and an up regulation after therapy. IL‐12p70 is a crucial factor in the differentiation of Th1 cell responses. Since CC chemokines are able to influence the T cell differentiation via cytokine secretion in antigen‐presenting cells, the production of CC chemokines in periodontitis was evaluated. Therefore WBCC were stimulated with LPS from Escherichia coli for 18 h and the levels of IL‐12p70 and CC chemokines were measured in the supernatants by ELISA. Untreated periodontitis patients released 2 fold more RANTES (regulated on activation normal T cell expressed and secreted) (P = 0·01) and lower levels of IL‐12p70 in comparison to controls (P < 0·05). A trend towards higher levels of macrophage chemoattractant protein‐1 (MCP‐1) (P = 0·07) was also seen in untreated periodontitis patients; while similar levels of monocyte derived chemokine (MDC) and macrophage inflammatory proteins‐1α and ‐1β (MIP‐1α and ‐1β) were found. After periodontal therapy no changes were seen with regard to MDC, MIP‐1α, MIP‐1β and RANTES, whereas the MCP‐1 levels decreased (P < 0·05) and the IL‐12p70 levels strongly increased (P < 0·01). The data showed a consistent inverse correlation between the levels of MCP‐1 and IL‐12p70, and their proportional changes after therapy correlated with the clinical inflammatory response after therapy. This indicates that the disease state regulates the release of IL‐12p70 and MCP‐1 in E. coli LPS‐stimulated WBCC. In contrast, the persistent augmented levels of RANTES after therapy are suggestive for an intrinsic behaviour.

Depressed Responsiveness of Peripheral Blood Mononuclear Cells to Heat-shock Proteins in Periodontitis Patients

The extensive homology between human and bacterial heat shock proteins (HSPs) may play a role in autoimmune reactions in periodontitis. Thus, we questioned whether peripheral blood mononuclear cell (PBMC) proliferative responses to HSPs are different between periodontitis patients and control subjects with gingivitis. The proliferative responses of PBMCs of patients (n = 10) and controls (n = 12) to recombinant mycobacterial HSP60 (MycHSP60) and HSP70 (MycHSP70), as well as recombinant human HSP60 (HumHSP60) and HSP70 (HumHSP70), were investigated. In addition, the proliferative responses to Candida albicans and purified protein derivatives of Mycobacterium (PPD) were included. Mean responses to HumHSP60, MycHSP60, and HumHSP70 were significantly lower for patients compared with controls. The responses to MycHSP70 showed a similar trend. However, when Candida and PPD were used as antigens, there was no difference in responses of the PBMCs between the periodontitis patients and controls. The level of IFN-γ in the supernatants of the cells stimulated with HSPs was lower in the patients compared with controls. This concurs with the current hypothesis that periodontitis patients have a depressed Th1 response. Furthermore, we found that with an increasing estimated subgingival bacterial load, periodontitis patients mount a decreasing immune response to HSPs, while the controls showed a positive correlation between these two parameters. From these findings, we speculate that poor reactivity to HSPs may be a susceptibility factor for destructive periodontal disease and may need to be considered in the pathogenesis of this condition.