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Gingival Crevicular Fluid – Overview

Is the measurement of gingival fluid easy, repeatable, and dependable?

1. Griffiths, G. Formation, collection and significance of gingival crevice fluid. Periodontl 2000. 2003; 31: 32-42

2. Goodson, J. Gingival crevice fluid flow. Periodontol 2000. 2003; 31:43-54

3. Delima, A, Van Dyke, T. Origin and function of the cellualr componenents in gingival crevice fluid. Peridontol 2000. 2003; 31: 55-76

4. Uitto V., Overall, C, McCulloch, C. Proteolytic host cell enzymes in gingvial crevice fluid. Periodontol 2000. 2003; 31:77-104

5. Eley, G., Cox, S. Proteolytic an hydrolytic enzymes from putative periodotal pathogens: characterization, molecular genetics, effects on host defecses and tissues and detection in gingival crevice fluid. Periodotol 2000. 2003; 31:105-24

Gingival Crevicular Fluid

Discuss the composition of gingival fluid.   What is the diagnostic significance of increased amounts of gingival fluid?

6. Orban, J, Stallard, R: Gingival crevicular fluid: A reliable predictor of gingvial health: J Periododontol 40:231-235, 1969

7. Hancock, E et al: The relationship between gingival crevicular fluid and gingival inflammation. A Clinical and histologic study. J Periodontol 50: 13-19, 1979

8. Offenbacher, S et al: The use of crevicular fluid prostaglandidn E2 levels as a predictor of periodontal attachment loss. J Periodont Res 21:101, 1986

9. Lamster, I et al: Development of a risk profile for periodontal disease: Microbial and host response factors. J Periodontol 65:511-520, 1994

10. Giannopoulou, C., Kamma J., Mombelli, A. Effect of inflammation, smoking and stress on gingival crevicular fluid cytokine level. J Clinical Periodontol 2003; 30: 145-153

11. Safkan-Sppparla, B., Sorsa, T et al: Collagenases in gingival crevicular fluid in type I diabetes mellitus. J Clin Periodontol 2006; 77:189-194

12. Bostanci N. et al. Ginvial crevicular fluidlevels of RANKL and OPG in periodontal diseases: Implications of the relative ratio. J Clin Periodontol 2007; 34:370-376

Passage of Antibiotics

Which antibiotics are concentrated in the gingival crevicular fluid?

13. Gordon JM, Walker CB, Murphy JC, Goodson JM, Socransky SS. Concentration of tetracycline in human gingival fluid after single doses. J Clin Periodontol8:117-121,1981.

14. Gordon JM, et al. Tetracycline: Levels achievable and in vitro effect on subgingival organisms. Part I. Concentrations in crevicular fluid after repeated doses. J. Periodontol. 52:609, 1981.

15. Pascale D, et al: Concentration of doxycycline in human gingival fluid. J. Clin. Periodontol. 13: 841- , 1986

16. Ciancio S, Mather M, McCullen J : An evaluation of minocycline in patients with periodontal disease. J. Periodontol. 51:530, 1980.

17. Britt MR, Pohlod DJ. Serum and crevicular fluid concentrations after a single dose of metronidazole. J. Periodontol. 57:104-107, 1986.

18. Conway TB, Beck FM, Walters JD. Gingival fluid ciprofloxacin levels at healthy and inflammed human periodontal sites. J Periodontol71:1448-1452, 2000.

Indicators of Disease Activity

Can gingival fluid contents be used to determine severity of periodontal conditions or disease activity?

19. Leibur E, Tuhkanen A, Pintson U, Soder P-O. Prostaglandin E2 levels in blood plasma and in crevicular fluid of advanced periodontitis patients before and after surgical therapy. Oral Diseases5:223-228, 1999.

20. Lamster IB, Oshrain RL, Harper DS, et al : Enzyme activity in crevicular fluid for detection and prediction of clinical attachment loss in patients with chronic adult periodontitis. Six month results. J. Periodontol. 59: 516-523, 1988.

21. Bader HI, Boyd RL. Long-term monitoring of adult periodontitis patients in supportive therapy: Correlation of gingival crevicular fluid proteases with probing attachment loss. J Clin Perio26:99-105,1999.

22. Lamster IB, Ahlo JK. Analysis of gingival crevicular fluid as applied to the diagnosis of oral and systemic diseases. Ann N Y Acad Sci. 1098:216-29, 2007. Review

Saliva

How does saliva play a role in a patient’s susceptibility or resistance to periodontal disease ?

23. Giannobile WV. Salivary diagnostics for periodontal diseases.J Am Dent Assoc. 2012 Oct;143(10 Suppl):6S-11S. Review.

25. Guentsch A, Preshaw PM, Bremer-Streck S, Klinger G, Glockmann E, Sigusch BW. Lipid peroxidation and antioxidant activity in saliva of periodontitis patients: effect of smoking and periodontal treatment. Clin Oral Investig. 12(4):345-52, 2008. Epub 2008 May 29.

26. Reher VG, Zenóbio EG, Costa FO, Reher P, Soares RV. Nitric oxide levels in saliva increase with severity of chronic periodontitis. J Oral Sci. 49(4):271-6. 2007

27. Frodge BD, Ebersole JL, Kryscio RJ, Thomas MV, Miller CS. Bone remodeling biomarkers of periodontal disease in saliva. J Periodontol. 79(10):1913-9, 2008.

28. Tobón-Arroyave SI, Jaramillo-González PE, Isaza-Guzmán DM. Correlation between salivary IL-1beta levels and periodontal clinical status. Arch Oral Biol. 53(4):346-52, 2008.

29. Rai B, Kharb S, Jain R, Anand SC. Biomarkers of periodontitis in oral fluids. J Oral Sci. 50(1):53-6, 2008

30. Miller CS, King CP Jr, Langub MC, Kryscio RJ, Thomas MV. Salivary biomarkers of existing periodontal disease: a cross-sectional study. J Am Dent Assoc. 137(3):322-9, 2006.

Gingival Crevicular Fluid – Overview

Is the measurement of gingival fluid easy, repeatable, and dependable?

Topic:Gingival crevicular fluid (GCF)

Authors:Griffiths, G.                                                           ARTICLE

Title: collection and significance of gingival crevice fluid.

Source: Periodontl 2000. 2003; 31: 32-42
Type:Discussion

Rating: Good

Keywords:gingival crevice fluid

Background:  The exact nature of GCF, its origins and composition has been subject of controversy.  The principle questions that remain unanswered are whether GCF is a transudate or an exudate, and whether GCF can form in a clinically healthy site.  The answers to these questions could yield therapeutic approaches.  An increase in GCF flow may have physical protective effects through flushing the pocket, as well as facilitating the passage of immunoglobulins.

Purpose:  To discuss the formation, collection, and significance of GCF.

Discussion: How is GCF formed?

• GCF is a result of an increase in the permeability of the vessels underlying junctional and sulcular epithelium.  Some irritation (chemical or mechanical) is necessary to induce production of GCF, and should therefore be considered a pathological phenomenon, but this stimulation is important for the maintenance of gingival health (e.g. transporting antibiotics, flushing effect). 

• GCF is an important component of the protective mechanisms of the crevicular regions due to its flushing effect which is capable of removing carbon particles and bacteria introduced into the gingival crevice.

• GCF may have an important role in transporting antibacterial substances to the gingival crevice.

Is GCF a transudate of interstitial fluid?

Controversy exists whereas GCF is a transudate or inflammatory exudate.

• Studies by Brill and Egelbergsupport that production of GCF was primarily a result of an increase in the permeability of the vessels underlying junctional and sulcular epithelium.

• An alternative theory arose from Alfano and Pashleysupporting that the initial fluid produced could simply represent interstitial fluid which appears in the crevice as a result of an osmotic gradient. This initial, pre-inflammatory fluid was considered to be atransudate, and, on stimulation, this changed to become an inflammatory exudate.

Collection Methods:

Several techniques have been employed and the technique chosen will depend upon the objectives of the study as each technique has advantages and disadvantages. Three basic categories:

1. Gingival washing: the gingival crevice is perfused by isotonic solution. The fluid collected represents a dilution of crevicular fluid and contain both cells and soluble constituents such as plasma proteins. This technique is valuable for harvesting cells from the gingival crevice region. Major disadvantage is that all fluid may not be recovered and accurate quantification of GCF volume or composition is not possible.

2. Capillary tubing and micropipettes: following isolation and drying of the site capillary tubes are inserted into the entrance of the gingival crevice. GCF from the crevice migrates into the tube and because the internal diameter is known the volume of the fluid collected can be accurately determined by measuring the distance which the GCF has migrated. However, it is difficult to collect an adequate volume of GCF in a short period unless the sites are inflamed and contain large quantities of GCF. It is difficult to conceive that holding a capillary tube at the entrance to the gingival crevice for long time ensures an atraumatic collection. Also, it is difficult to remove the complete sample from the tubing.

3. Absorbent filter paper strips: quick and easy to use. Can be applied to individual sites and is possibly the least traumatic.

Methods of collection can be broadly divided into intracrevicular and extracrevicular techniques. The former depends on the strip being inserted into the gingival crevice, whereas in the latter the strips are overlaid on the gingival crevice region in an attempt to minimize trauma. The intracrevicular methodis the method used most frequently and can be further subdivided depending upon whether the strip is inserted just at the entrance of the crevice or periodontal pocket or whether the strip is inserted to the base of the pocket or until minimum resistance is felt.

(a) extracrevicular method; (b) intracrevicular method ‘superficial’ (c) intracrevicular method ‘deep’

• Collection and quantification of GCF is a very sensitive procedure and all techniques have limitations and flaws (contamination, inconsistent sampling times, volume determination, recovery from strips). 

• The method of collecting GCF may have a significant effect upon the nature collected and will therefore prejudice results assessing diagnostic markers

Association of GCF with health or disease: The association of an increased volume of GCF with an increase in the severity of inflammation is well supported by evidence from literature.

Topic:Gingival crevicular fluid

Authors:Goodson, J                                                          ARTICLE

Title:Gingival crevice fluid flow

Source:J. Periodontol 2000. 2003; 31:43-54

Type:Discussion article

Rating: Good

Keywords:Gingival fluid

Purpose: To focus attention on the importance of GCF flow and the effect that small streams of fluid flowing out of the periodontal pocket have on the periodontal environment.

Discussion:

GCF flow(or flow rate): is the process of fluid moving into and out of the gingival crevice or pocket.

Fluid flow:is a rate measure of the volume that crosses a defined boundary over a given time.

Resting volumeis the amount of fluid within a given space.

3 Methods of Measurementare available to differentiate fluid flow from the resting GCF volume.

Method 1: Samples are collected(w/ filter paper strips) rapidlyunder strict timing protocol so that the resting volume is removed by the first sampleand the volume of the newly formed GCF can be measured in subsequent samples. The key to this measurement is to select a sampling time that is small enough so that the resting volume of the pocket is not allowed to re-establish. Ideally, one would remove the entire contents of the pocket with the first sample so that all subsequent samples would be repetitive estimates of the GCF volume flow over the sampling time.

Method 2: Collect samples(w/ filter paper strips) after equilibrium has been re-established in the pocket over several different time intervals. In this case, each GCF sample includes both the resting volume (Vr) and the volume of GCF that entered the pocket over the sampling period lends itself directly to linear regression analysis in which the volume and time of each sample contribute to the analysis to determine the slope which is the GCF influx (fi) and the intercept which is the resting volume of the pocket (Vr).

Method 3: Measure the equilibrium concentration of a marker substance pumped into a pocket at a constant rate. By pumping a marker substance (ie Tetracycline) into a periodontal pocket at a constant rate, an equilibrium concentration will be established which is the result of the fluid flow rate and the pump delivery rate. To date, no published study has been conducted to evaluate GCF flow in this manner.

Lamster et al:

Described changes in GCF sample volumes taken during experimental gingivitis that are directly amenable to analysis by method 1. In the GCF sampling protocol of this study, a filter paper strip was placed in the sulcus for 30s and removed for volume determination (V1). Thirty seconds was allowed to elapse and the GCF volume was determined by introducing a second filter paper strip into the site for 3s (V2). The results of this study clearly indicated that the two sample volumes collected increased linearly over the period of development of experimental gingivitis. The GCF flow increases as inflammation becomes more severe and vascular permeability increases.

• Studies showthat GCF flow as an outcome variable for therapy studies does not have the statistical power of either pocket depth reduction or attachment level gain.

One site from each of 56 systemically healthy subjects with periodontal disease was assigned to each clinical category (Health, gingivitis, mod Periodontitis and advanced periodontitis). The data indicate that broadly defined categories of health and disease can be distinguished by differences in GCF flow.

• By this analysis, the GCF flow at healthy sites was significantly less than all other categories.

• The GCF flow at sites with gingivitis was significantly less than the GCFflow at advanced periodontitis sites.

• Thedifference between the GCF flow at gingivitis sites and sites with moderate periodontitis was not statistically significant.

Conclusion:Given the evidence that change in GCF flow may be a sensitive measure of local inflammation, this type of evaluation could increase the diagnostic potential of this measure being used chair-side. GCF flow measurement could provide added benefit in establishing a diagnosis and monitoring the response to therapy.

Topic:Gingival crevicular fluid

Authors:Delima, A, Van Dyke, T.                                                          ARTICLE

Title:Origin and function of the cellualr componenents in gingival crevice fluid.

Source:Peridontol 2000. 2003; 31: 55-76

Type:Discussion/Review

Rating:Good

Keywords:gingival crevicular fluid

Purpose:To review the origin and function of the cellular components in gingival crevicular fluid

Discussion:Periodontitis is initiated by bacterial colonization, followed by proliferation, and extension of the plaque into the subgingival environment. While diseases of the periodontium are bacterial in origin, the extent and severity of the disease depend upon the interaction between pathologic microbes and host response. The outflow of GCF helps to cleanse the dentogingival space of non-adherent microbes and to reduce the concentrations of toxins and byproducts. GCF contains microbes and antimicrobial compounds and enzymes directed at them. We often think about the flushing mechanism of GCF, but it also serves as an entry point to bacteria. One of the initial responses of the host to bacterial plaque is an increase in the vascular permeability of the subepithelial blood vessels. This leads to edema in the gingival crevice (via the JE) and results in increased crevicular fluid flow. Since this exudate is essentially a growth medium that supports host cells and tissues, the GCF can also act as an excellent source of nutrients for subgingival microbes and may actually contain factors that are necessary for the proliferation of some pathologic bacterial species.

The GCF is rich in cellular elements and also delivers antibodies and the complement system to fight the plaque front. The epithelia of the sulcus are constantly renewing and this rapid turnover appears to aid in the clearance of bacteria that adhere to these cells. One major set of cells found here are the PMN’s – these are the major cellular defense system in the gingival crevice. These cells leave the connective tissue and migrate through the JE into the crevicular space where they accumulate at the interface of the subgingival plaque. PMN’s compromise about 90% of the cells in the GCF, and their defense mechanism includes phagocytosis and release of bactericidal enzymes. It also has been shown that the release of granules from PMN’s that are capable of disengaging bacterial plaque adherence to the tooth. Other cells present in the GCF include monocytes and macrophages. These are usually seen against the oral epithelium, and they function in the cellular defense and acquired immunity of the periodontal tissues.

Conclusion:The nature and extent of bacterial challenge is modulated and attenuated by the host immune response. Inflammatory and immune responses can also contribute to the destruction of host tissues. The narrow balance between periodontal homeostasis and disease depends upon a qualitatively and quantitatively appropriate response of the host defense mechanism to infection of the periodontal tissue. The outflow of GCF helps to cleanse the dentogingival space of non-adherent microbes and to reduce the concentrations of toxins and metabolic byproducts. Constant cellular turnover and the presence of PMNs help to aid in the clearance and protection of the sulcus. Understanding the components of GCF will help to clarify the initial events in the pathogenesis of periodontal disease and aid in the monitoring of the disease process.

Topic:GCF

Authors: Uitto V., Overall, C, McCulloch, C                                                          ARTICLE

Title:Proteolytic host cell enzymes in gingvial crevice fluid.

Source:Periodontol 2000. 2003; 31:77-104

Type:Discussion

Rating: Good

Keywords:GCF

Purpose: This is a review of literature on findings on host cell-derived enzymes that relate to periodontal disease processes. Special emphasis is placed on MMPs. The potential use of tissue-derived GCF in enzymes in clinical periodontology is also discussed.

Discussion: Neutrophils form the first line of defense and are attracted to infected tissues by chemoattractants released from bacteria, host cells or degraded tissue. Over 90% of leukocytes in GCF are neutrophils.

They contain vesicles where molecules used for host defense are stored. These granules are generally classified into azurophilic (primary), specific (secondary) and gelatinase (tertiary) types. Gelatinase granules are released first, then specific and lastly the azurophilic. The major MMPs in neutrophils are MMP-8 and -9.

The serine proteinases (neutrophil elastase, cathepsin G and proteinase 3) are secreted from the azurophilic granules during phagocytosis, stimulation and cell lysis. Stimulation by LPS, TNF-and IL-8 results in increased (20-fold) binding of these proteinases with cell membranes. Their actions is inhibited by the serpins. When there is increased population of neutrophils there is increased concentration of active forms of the enzymes in the tissues, causing degradations of extracellular matrix. Elastase and cathepsin G are capable of activating epithelial cells to produce IL-8, IL-6 and prostaglandin E2, which further increase chemotaxis, immune cell proliferation, and tissue degradation in inflamed tissues.

Epithelial cell proteinases: Although epithelial cells were considered as relatively passive cells whose function was to protect body surfaces, it now clear that they strongly respond to exogenous factors and therefore exhibit different morphotypes. When activated they behave aggressively by migrating, proliferating and producing various cytokines and proteolytic enzymes. They were found to produce collagenases (MMP-13, produced by the basal cells of pocket epithelium) when stimulated in vitro by TNF-TGF-or keratinocyte growth factor. MMPs -2, -9, -7 have also been found to being produced by epithelial cells.

Fibroblast proteinases: Fibroblasts are responsible for the turnover of connective tissue in normally functioning tissues and they have therefore the capacity to degrade all the components of CT. The major MMPs produced are 1, 2, 13, 3, 14. It appears that MMP- 1 is secreted in the crevicular fluid of patients with localized juvenile periodontitis, while neutrophil type collagenase MMP-8 is prevalent in adult periodontitis. Expression of MMPs can be regulated by the protein composition of the extracellular matrix and following ligation of integrin receptors.

Matrix metalloproteinases: MMPs form the most important family of proteinases that participate in the normal turnover of periodontal tissues as well as their degradative aspects during periodontal diseases. As MMPs can potentially destroy tissues, their activity is strictly controlled at different levels. First, specific inhibition of MMPs can be mediated by the four members of the tissue inhibitor of metalloproteinase (TIMP) family, proteins that regulate the extracellular activity of MMPs. Second, MMPs are synthesized as latent zymogens. Activation of MMP zymogens is a critical step for regulating MMP activity and hence the composition, structure, and function of periodontal connective tissue matrices. Third, most MMPs are secreted from cells as a soluble proform. For some soluble MMPs, activation occurs at the cell surface following proteolytic cleavage by MT-MMPs, often in a TIMP dependent pathway. For other MMPs, activation occurs in the extracellular environment in an activation cascade initiated by tissue proteinases, such as plasmin, kallikrein, and tryptase, a process that is often amplified by the activated MMPs functioning as pro-MMP activators.

TIMPs:Inhibition of MMPs by TIMPs is largely interchangeable, except for the MT-MMPs, which are not inhibited by TIMP-1. TIMP-2 also plays a paradoxical role in mediating MMP-2 activation.

Detection methods for GCF MMPs: collagenases (MMP-1, -8, 13), gelatinases (MMP-2, -9), and stromelysin (MMP-3) have all been measured in GCF. Immunological assays, including ELISA and immunoblots, offer highly sensitive and specific testing methods. Immunoblots are time consuming, ELISA using antibodies is accurate and significant numbers of anti-MMPs exist on the market. Although these methods of detection are highly specific, they might not be able to distinguish between active and inactive MMPs, since MMPs can still bind the substrate without cleavage. Immunohistochemical examinations can help identify MMPs but without actually quantifying them. Another possible but untried method would be neo-epitope antibodies that can detect degradation fragments from matrix proteins or MMPs, thus help identify, quantify, and determine activity.

Substrate degradation: measure primarily the ability of MMPs to degrade the substrate, estimating enzyme activity depending on the relative abundance of the substrate degradation products by dot assays.sodium dodecyl sulfate–polyacrylamide gel electrophoresis, radioactivity, zymography, or fluorescence. The rationale for examining enzyme activity compared to the presence or abundance of MMPs (measured typically by immunochemical methods) is that in periodontitis the temporal progression of lesions is more strongly associated with the presence of active MMPs than with the total amount of enzyme. Collagen degradation products: measuring collagen metabolites in GCF can help and more directly quantify MMPs activity

GCF enzymes as indicators of periodontal health:it has been shown that PMNs enzymes detected in the GCF reflect the number of leukocytes rather than tissue destructions, so directing our attention to MMP-13 for example rather than MMP-8 (collagenase-2) appears more rational, since MMP-13 (collagenase-3) can also be produced by fibroblasts and pocket epithelial cells during tissue destruction. Neutrophil elastase, and B-Glucuronidase have been extensively studied as well, both are involved in tissue destruction. A simple mouth rinse assay has determined that total crevicular fluid elastase levels were indicated that there was a good correlation between the oral elastase activity and the number of deep pockets and the average CPITN scores. Longitudinal studies have shown the risk ratio of clinical attachment loss in patients with high B-glucuronidase activity in GCF is about 10-fold, this relation is also high when considering progressive sites vs. non progressive. Another test that has been developed is detection of aspartate aminotransferase activity GCF, this test yielded an OR of 12 for attachment loss.

Topic:Host defense

Author:Eley, G., Cox, S.                                                           ARTICLE

Title:Proteolytic and hydrolytic enzymes from putative periodontal pathogens: characterization, molecular genetics, effects on host defenses and tissues and detection in gingival crevice fluid.

Source:Periodontology 2000. 2003; 31:105-24

Type:Discussion article

Rating:Good

Keywords:proteolytic, hydrolytic, enzymatic reactions, host defense, pathogenicity

Purpose:Discussion article that describes the characteristics of proteolytic and hydrolytic enzymes produced by various bacteria, (Pg, Pi, Aa, Fn, Treponema, Eikenella corrodens, and capnocytophaga).

Discussion:

• All of the bacteria discussed produce both proteolytic and hydrolytic enzymes (degrade non-proteinaceous components of connective tissue). Proteases are more critical to bacterial survival since most of their nutrition is obtained from protein sources. P. gingivalisproduces and releases a greater number of proteases with more protease activity than any other bacteria.

• The genes encoding for bacterial proteases have been identified for arg-gingipain A and B, lys-gingipain, collagenolytic proteases tripsine and chymotripsine-like protease from T. denticola. These proteases are able to degrade immunoglobulins, clotting factors, proteinase inhibitor and components of host CT. All of these enzymes are released in the GCF.

• P. gingivalis appears to produce two cysteine proteinases with trypsin-like activity (cleaves BANA). One of these is arginine specific (arg-gingipains A and B) and the other is lysine specific (lys-gingipain), deriving from rgpA, rgpB and kgp genes respectively.

• These enzymes have collagenolytic activities (Type I and IV) increasing host tissue destruction. RgpA degrades IgA1, IgA2 and IgG, reducing the host response. It also degrades complement component C3 reducing opsonization. RgpA and kgp degrade C5 and release C5a, stimulating inflammation. P.g. inhibits PMN migration and diapedesis by degrading Il-8 and intracellular adhesion molecule 1 (ICAM-1).

• Furthermore, P.g. cysteine proteinases can degrade the lysozyme that is found in the GCF and saliva.

• Gingipains activate pre-kallikrein system, leading to bradykinin formation and subsequent vasodilation. This process increase GCF flow, thus increasing the nutrients in the crevice. P.g. also degrades fibrinogen which increases the local clotting time and as a result leads to gingival bleeding. This provides a rich source of haem and iron required by the bacterium for its survival.

• P.g. also releases hydrolytic enzymes, (hyalouronidase and chondroitinase) which hydrolyze the glycozaminoglycan components of proteoglycans.

• P.intermedia and P.nigresens, Treponema species, Capnocytophaga species, A.a., F. nucleatum, C. rectus and E.corrodenshave been also shown to have trypsin-like activity, but all is very weak compared to P.g.

• They have proteolytic activity for various components of the ECM (laminin, gelatin and fibronectin). Their proteases are able to degrade IgG and fibrinogen. F. nucleatum and E.corrodens are the weakest species. Bacterial proteases are released in the GCF and can be detected on filter paper strips. Selective biochemical assays have been developed to detect and distinguish between those proteases. Cross sectional study showed 93.81% positive prediction and 100% negative prediction for arg-gingipains, and 100% negative prediction for dipeptidylpeptidases for all incidence of rapid episodic CAL loss in a 3-month period. All comparisons of mean patient values in patients with or without CAL loss were SS.

BL:GCF arg-gingipain appears to be an excellent predictor and GCF dipeptidylpeptidase is a moderately good predictor of future progressive CAL loss. A chair-side system has been developed to detect these bacterial proteases.

Gingival Crevicular Fluid

Discuss the composition of gingival fluid.

What is the diagnostic significance of increased amounts of gingival fluid?

Topic:Gingival crevicular fluid

Authors:Orban, J, Stallard, R                                                           ARTICLE

Title: Gingival crevicular fluid: A reliable predictor of gingvial health

Source:J Periododontol 40:231-235, 1969

Type:Clinical study

Rating: Good

Keywords: gingival crevicular fluid, hyaluronidase, biopsy

Purpose:  To evaluate the accuracy of GCF as an indicator of gingival inflammation.

Method: Dental school patients were chosen at random and evaluated by using Ramfjord’s criteria for Perio Dx Index (PDI) & Greene & Vermillion’s Oral Hygiene Index-Simplified (OHI-S).  GCF measurements were made using filter strips 1mm wide and several mm long, placed intracrevicularly for 3 minutes, removed and allowed to dry. The area that absorbed crevicular fluid was stained by 2% ninhydrin solution. The area stained was then measured and mean scores were calculated.  Calculus was scored for OHI-S and plaque for Ramfjord’s Index using disclosing tablets.  Biopsies taken from distal half of each area evaluated. Each biopsy was evaluated according to amount and extent of inflammatory infiltrate and scored on a 0-10 scale.

Results:  From the data obtained it was apparent that GCF scores were not directly related to biopsy scores. Thus, crevicular fluid did not prove to be an accurate predictor of gingival inflammation. Plaque scores revealed a high degree of correlation on both an individual and overall evaluation when compared to biopsy scores of inflamed gingiva.

Discussion:Enzymes commonly found in plaque, primarily hyaluronidase, cause an increase in crevicular fluid flow without altering the inflammatory condition of the gingiva. Apparently, the intercellular cementing substance is modified, resulting in an increased permeability of the crevicular epithelium. Other factors including chewing, brushing, gingival massage, circadian rhythm and hormones all affect crevicular fluid flow without necessarily altering the inflammatory condition of the gingival tissues. However, it is a measure of the intactness and permeability of the gingival tissuesdue to previously mentioned factors. Further, as a single measurement on a patient, crevicular fluid recordings may have little significant value. Consecutive measurements, however, are of value in relating the response of the gingival tissues to environmental, physiologic and pathologic conditions and changes.

Conclusion: Dental plaque is a better indicator of the inflammatory status of the gingival tissues than GCF levels.

Topic:gingival fluid

Authors: Hancock EB, Cray RJ, O’Leary TJ.                                                          ARTICLE

Title:The relationship between gingival crevicular fluid and gingival inflammation. A clinical and histologic study.

Source:J Periodontol. 1979Jan;50(1):13-9. DOI: 10.1902/jop.1979.50.1.13

Type:clinical

Rating: good

Keywords:GCF, gingival crevicular fluid, gingival inflammation,

Background:Past research reported that the flow of GCF begins a few days before other clinical signs of inflammation are apparent. Therefore, it is suggested that its flow might be measured to evaluate gingival inflammation.

Purpose: To evaluate the relationship between GI, GCF flow, and histology in order to see if GCF could be an indicator of disease severity in form of gingival inflammation.

Methods: 60 patients (26M, 34F, 18-72 years old); considered themselves in good health without known systemic diseases. No periodontal therapy within the last 90 days. Teeth #5-#12 were examined in each patient and evaluated for selection by the following criteria:

1) Presence of an adequate zone of gingiva, 2) No cervical or interproximal carious lesions. 3) No defective interproximal restorations. 4) No facial cervical restorations. 5) No acute gingivitis or periodontitis condition.

Data was collected on 57 sites; amount of GCF flow, gingival health status, GI, histologic evaluation, and histologic evaluation. After isolation with cotton rolls, GCF collected from mid-facial with filter paper in the opening of the gingival crevice for 3 min. A second sample was taken to verify fluid flow rate. Gingiva at these areas was evaluated for inflammation. GI assessed using modified GI by Löe. One tooth from each patient had gingival biopsy, trying to take equal numbers of healthy and inflamed tissues. Histology looked for inflammatory cell density. Histologic analysis looked at extent of inflammatory infiltrate using a gravimetric method

Results: results show that GCF flow tended to increase as the degree of inflammation became more severe. The quantity of GCF, by itself, was a poor indicator of the severity of gingival inflammation.The highest correlation was seen between GI and the gingival status (mainly BOP based). A high correlation was seen between clinical and histologic scores, but a very weak correlation was seen between GCF and either of these factors.

Conclusion: GCF was weakly correlated with GI and histologic evidence of inflammation; it did, however, tend to increase when inflammation increased.

Topic:Indices

Author: Offenbacher S.                                                          ARTICLE

Title:The use of Crevicular fluid prostaglandin E2 levels as a predictor of periodontal attachment loss

Source:J Periodont Res 21:101, 1986

Type:Longitudinal study

Rating: Good

Keywords:Indices; prostaglandin E2; periodontal disease

Purpose:To report results of a three-year longitudinal study, which demonstrate that crevicular fluid PGE levels can be used to reliably indicate ongoing tissue destruction, and may also be used to predict future acute periodontal attachment loss.

Methods:7 healthy patients, 41 adult periodontitis patients and 12 juvenile periodontitis patients were assessed. All patients had a negative history of major systemic illness. All patients had at least 20 remaining teeth. Data was obtained over a period of 18 months up to 3 years for analysis. CF fluid was collected and clinical measurements (redness, edema, suppuration, BOP, pain on probing, Attach loss) were obtained at baseline and repeated one week later. SRP was performed on all diseased patients. CF collection and clinical measurements were repeated one month following initial therapy. Patients were placed on a three-month recall and CF collection was repeated at each maintenance. When a site demonstrated a statistically significant loss of periodontal attachment, after the data collection (CF and clinical parameters), local curettage and root planning was performed. One month after therapy data was again collected, and then patients were exited from the study and referred to periodontist for additional therapy. During the visit at which AL was identified, 6 consecutive CF samples were obtained at attachment loss site and 6 CF samples at the contralateral control site. Mean CF-PGE level was determined.

Results:The mean CF-PGE2 of the healthy individuals(26.9 ng/mL) was significantly lower than the one of the adult periodontitis patients (56.6± 5.4 ng/mL) and the juvenile periodontitis patients(139.4±15.3 ng/mL). The CF- PGE2 was also elevated at the time of detectable ALcomparing to the cross-sectional adult periodontitis MCF-PGE.

It was observed that CF-PGE levels were increased prior to the development of the acute lesion (immediately preceding the AL episode). There was a high degree of overall and specific agreement between high CF-PGE2 levels and attachment loss. The elevated levels of CF-PGE are highly specific (0.94) and sensitive (0.76) of ongoing AL.

Conclusion: PGE levels in GCF reliably indicate ongoing disease activity and could predict upcoming attachment loss.

Topic:risk factors

Authors: Lamster I, et al                                                          ARTICLE

Title:Development of a risk profile for periodontal disease: Microbial and host response factors

Source:J Periodontol 65:511-520, 1994

Type:report

Rating: Good

Keywords:periodontitis/microbiology; periodontal diseases/microbiology; risk factors, host response, gingival crevicular fluid, glucuronidase

Purpose:To list risk factors associated with the host-microbial interaction in periodontal disease

Conclusion:4 factors and their association with active chronic periodontal disease were explored in this review: Elevated GCF levels of β-glucuronidase (a lysosomal hydrolase that can serve as a marker for primary granule release from PMNs), elevated levels of periodontal pathogens, reduced levels of IgA in GCF, and reduced levels of serum IgG antibody to putative periodontal pathogens. These pathogen associated risk factors, as well as patient- associated risk factors (DM, smoking), can provide diagnostic information to aid in the treatment of patients with periodontal disease.

Saliva

How does saliva play a role in a patient’s susceptibility or resistance to periodontal disease ?

Topic:Smoking on gingival crevicular fluid

Authors:Giannopoulou, C., Kamma J., Mombelli                                                          ARTICLE

Title: A. Effect of inflammation, smoking and stress on gingival crevicular fluid cytokine level.

Source: J Clinical Periodontol 2003; 30: 145-153
Type:Clinical study

Rating: Good

Keywords:smoking, interleukins, gingival crevicular fluid

Purpose:To determine the levels of interleukin (IL)-1β, IL-4, IL-6 and IL-8 in gingival crevicular fluid of periodontally healthy and diseased individuals and to study their association to environmental factors such as smoking and stress.

Material and method:

• A total of 80 patients from a private periodontal practice were included in the study:

• 20 patients per disease category: aggressive periodontitis (EOP), chronic adult periodontitis (AP), gingivitis (G) healthy periodontium (H).

• PD, AL, Pl, BOP, suppuration, and smoking and stress information were recorded at initial visit and after GCF sampling. Full mouth standardized periapical radiographs were taken and bone loss was assessed.

• GCF was collected from four sites per patient, randomly selected in each quadrant by means of durapore filter membranes. After isolation of the test sites from saliva, a first Durapore strip was inserted 1mm into the sulcus or pocket and left in place for 15s. Three minutes after removal of the first strip, a second Durapore strip was similarly inserted in the same site for 15s. The two strips were then placed into a microcentrifuge tube and immediately frozen until the day of the analysis. In case of visible contamination with blood, the strips were discarded.

• The contents of IL- 1β, IL-4, IL-6 and IL-8 were measured in 320 samples by use of commercially available sandwich enzyme-linked immune adsorbent assays.

Results:In subjects with periodontitis, the total amounts of IL-1β, IL-6 and IL-8were significantly elevated compared to healthy subjects.  IL-4showed an inverse relationship to periodontal status and higher amounts were found in the healthy group. The amounts of all four cytokines were positively correlated with probing depths. IL-4, IL-6 and IL-8 were significantly correlated to smoking while stress was associated withIL-1β, IL-6 and IL-8levels.

Conclusion:IL-1β, IL-6 and IL-8 reflect the activity of periodontal destruction, whereas IL-4 shows an inverse correlation to it.

Topic: Gingival Crevicular Fluid

Authors:Safkan-Sppparla, B., Sorsa, T                                                           ARTICLE

Title:Collagenases in gingival crevicular fluid in type I diabetes mellitus.

Source:Implant Dent. 2008 Mar;17(1):16-23

Type:Clinical study

Reviewer:Laura Porras

Rating: Good

Keywords:

Purpose: To analyze GCF collagenases of poorly and well-controlled type 1 DM and chronic periodontitis subjects compared to non-