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Biomedical subjects

K Suomalainen

Publications and source records attributed to K Suomalainen.

At least 19 recordsLinked to original sources
PubMed2006

Monitoring periodontal disease status in smokers and nonsmokers using a gingival crevicular fluid matrix metalloproteinase-8-specific chair-side test.

BACKGROUND AND OBJECTIVE: With current periodontal diagnostic tools it is difficult to identify susceptible individuals or sites at risk. The aim of this study was to evaluate the efficacy of the matrix metalloproteinase (MMP)-8-specific chair-side dip-stick test in longitudinally monitoring the periodontal status of smoking (S) and nonsmoking (NS) patients with chronic periodontitis, using their gingival crevicular fluid (GCF) MMP-8 concentrations. MATERIAL AND METHODS: Clinical parameters, MMP-8 test results and concentrations were monitored in 16 patients after initial treatment and in 15 patients after scaling and root planing (SRP), every other month, over a 12-mo time period. Progressing and stable sites, and sites with exceptionally high MMP-8 concentrations, were analysed in smokers and nonsmokers. RESULTS: SRP reduced the mean GCF MMP-8 levels, test scores, probing depth (PD), attachment loss (AL) and bleeding on probing (BOP). In sites of periodontal disease progression, the distribution of MMP-8 concentrations was broader than in stable sites, indicating a tendency for elevated concentrations in patients with periodontal disease. The mean MMP-8 concentrations in smokers were lower than in nonsmokers, but in smokers' and nonsmokers' sites with progressive disease, MMP-8 concentrations were similar. Sites with exceptionally elevated MMP-8 concentrations were clustered in smokers who also showed a poor response to SRP. In these sites, the MMP-8 concentration did not decrease with SRP and these sites were easily identified by the MMP-8 test. CONCLUSION: Persistently elevated GCF MMP-8 concentrations may indicate sites at risk, as well as patients with poor response to conventional periodontal treatment (e.g. SRP). MMP-8 testing may be useful as an adjunct to traditional periodontal diagnostic methods during the maintenance phase.

Biomarkers↗
PubMed1996

Peroxidases, lactoferrin and lysozyme in peripheral blood neutrophils, gingival crevicular fluid and whole saliva of patients with localized juvenile periodontitis.

OBJECTIVE: The aim of this study was to examine the longitudinal association of selected non-immune anti-microbial host factors (peroxidases, lysozyme and lactoferrin) to the localized juvenile periodontitis (LJP) disease status. MATERIALS AND METHODS: Peroxidases, lysozyme and lactoferrin were quantitated from seven patients with LJP before and after periodontal therapy. Analyses were performed from simultaneously collected samples of peripheral blood polymorphonuclear leukocytes (PMNs), gingival crevicular fluid (GCF from diseased sites) and paraffin-stimulated whole saliva. Similar assays were done also from seven periodontally healthy controls. RESULTS: During untreated phase of LJP myeloperoxidase, lysozyme and lactoferrin concentrations were remarkably elevated in peripheral blood PMNs, also reflected in their high concentrations in GCF. All these values normalised with respect to healthy controls during the periodontal therapy. No similar longitudinal changes were seen in whole saliva but during therapy salivary peroxidase concentrations declined below the control values, in accordance with our previous observations in parotid saliva samples of LJP patients. CONCLUSIONS: In LJP the concentrations of lysozyme, lactoferrin and myeloperoxidase are significantly elevated in peripheral blood PMNs, also reflected in GCF. During periodontal therapy these values decline and approach those observed in healthy controls. No similar changes are seen in stimulated whole saliva.

Adolescent↗
PubMed1995

The width of radiologically-defined attached gingiva over deciduous teeth.

The aim of the present cross-sectional study was to radiologically investigate the continuous eruption process in the deciduous dentition by assessing the difference in the width of radiologically-defined attached gingiva (RAG) in 6-year-old and 10-year-old children. The group of 6-year-olds had predominantly deciduous teeth and the 10-year-olds were in their mixed dentition period. The mucogingival junction was revealed with Schiller's iodine solution and marked mid-labially along the long axis of each tooth with a piece of metal wire prior to taking panoramic radiographs. The width of RAG over deciduous canines and molars was measured from the cementoenamel junction to the mucogingival junction. A significant increase in the width of RAG was found from 6 to 10 years of age.

Child↗
PubMed1994

Collagenase, gelatinase and elastase activities in sulcular fluid of osseointegrated implants and natural teeth.

Proteinases play a key rôle in the physiological degradation and remodelling of the periodontal tissues. The rôle of these enzymes in tissue remodelling remodelling in connection with the insertion of dental endosseous implants has not been elucidated. Therefore, the aim of the present study was to identify the eventual presence of collagenase, gelatinase and elastase activities in periimplant sulcus fluid (PISF) of osseointegrated implants. Gelatinolytic activity in the samples was studied with gelatin-zymograms. Collagenase activity and its susceptibility to tetracycline-inhibition were monitored with SDS-polyacrylamide gel electrophoresis and laser densitometry, and elastase activity with synthetic substrate. Low activities of elastase and collagenase were detected in both PISF of osseointegrated implant patients and gingival crevicular fluid (GCF) of the control patients whereas significantly higher activities were detected in GCF of adult periodontitis patients. Also the profiles of gelatinases were similar in PISF of osseointegrated implant patients and GCF of the controls, but differed from the profile of active gelatinases present in GCF of adult periodontitis patients. The similar activities/characteristics of these proteinases in both periimplant sulcus fluid of healthy dental implants and GCF of healthy natural teeth suggest that they comprise the major proteinases for both periodontal and periimplant tissue remodelling or destruction.

Adult↗
PubMed1993

Doxycycline protects serum alpha-1-antitrypsin from human neutrophil collagenase.

Interstitial collagenases, members of the matrix metalloproteinase family, are key initiators of collagen destruction during various disorders such as rheumatoid arthritis. Recently interstitial collagenases were found to efficiently degrade an additional non-collagenous substrate, the serum alpha-1-antitrypsin (AAT also called alpha-1-proteinase inhibitor or serpin). Serpins are major endogenous inhibitors of serine proteinases, particularly neutrophil elastase. Of relevance to neutrophil-mediated collagen degradation, the tetracycline family of antibiotics are now known to inhibit inhibit mammalian collagenases by a mechanism unrelated to their antimicrobial activity. This study identifies an additional mechanism by which tetracyclines may retard tissue breakdown during inflammatory diseases. Doxycycline, added to the reaction mixture as in concentrations as low as 10 microM, which correspond to levels of the drug readily achieved in vivo, produced detectable inhibition of serpinase activity of neutrophil collagenase, although levels of 50-100 microM or greater were required to reduce AAT degradation more than 75%. The concentration of doxycycline to inhibit 50% (IC50 of serpinase activity) of AAT degradation by neutrophil collagenase was found to approximate 20 microM, a value similar to the IC50 for doxycycline required to inhibit collagen degradation by neutrophil collagenase. Doxycycline was also found to inhibit at cell level neutrophil-mediated degradation of AAT. The protection of bodies' AAT-shield from serpinolytic activity of collagenase would result in inhibition of serine proteinases such as neutrophil elastase. Tetracyclines may thus protect matrix constituents from a wider spectrum of neutral proteases than previously recognized, not just from the matrix metalloproteinases collagenase and gelatinase.

Collagenases↗
PubMed1993

Salivary collagenase, elastase- and trypsin-like proteases as biochemical markers of periodontal tissue destruction in adult and localized juvenile periodontitis.

The profile of salivary proteases and their cellular origin, with special reference to polymorphonuclear leukocytes and bacteria, was studied in localized juvenile periodontitis and compared with adult periodontitis and healthy controls. General proteolytic activity in saliva as well as collagenase, elastase-like and trypsin-like activity was measured. In addition, the sensitivity of salivary collagenase of patients with localized juvenile periodontitis to doxycycline inhibition was studied. The saliva of localized juvenile periodontitis patients contained low amounts of collagenase compared with adult periodontitis saliva, and almost all salivary collagenase was found to exist in endogenously active form, as was found to be the case also in adult periodontitis patients and healthy controls. The salivary collagenase of localized juvenile periodontitis patients was relatively insensitive to 100 mumol/l doxycycline but was completely inhibited by 600 mumol/l doxycycline, reflecting rather matrix metalloproteinase-1 (fibroblast-type) than matrix metalloproteinase-8 (polymorphonuclear leukocyte) enzyme. The saliva of localized juvenile periodontitis patients also contained low amounts of elastase-like activity compared with the saliva of untreated adult periodontitis patients. Scaling and root planing caused a significant decrease in elastase-like activity in the saliva of adult periodontitis patients. General proteolytic and trypsin-like activities were also low in the saliva of localized juvenile periodontitis patients. Furthermore, the reducing agent beta-mercaptoethanol did not activate or inhibit the salivary trypsin-like activity of localized juvenile periodontitis or adult periodontitis patients, although the reductant readily activated partially purified Porphyromonas gingivalis trypsin-like protease in a characteristic manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Aggressive Periodontitis↗
PubMed1993

Doxycycline in the protection of serum alpha-1-antitrypsin from human neutrophil collagenase and gelatinase.

The concentration of doxycycline required to inhibit 50% (50% inhibitory concentration for serpinase activity) of alpha-1-antitrypsin degradation by purified neutrophil collagenase was found to be approximately 20 microM, a value similar to the 50% inhibitory concentration of doxycycline required to inhibit collagen degradation by neutrophil collagenase. Doxycycline also efficiently inhibited phorbol myristate acetate-triggered neutrophil-mediated degradation of alpha-1-antitrypsin. This suggests that doxycycline can protect alpha-1-antitrypsin from collagenase and gelatinase in the presence of other proteases and biologically active molecules that are released by triggered neutrophils. The protection of a body's alpha-1-antitrypsin shield from serpinolytic activity of collagenase and matrix metallproteinases can result in inhibition of serine proteases such as neutrophil elastase. Tetracyclines may thus protect matrix constituents from a wider spectrum of neutral proteases than previously recognized, not just from the matrix metalloproteinases collagenase and gelatinase.

Collagenases↗
PubMed1993

Tetracycline inhibition and the cellular source of collagenase in gingival crevicular fluid in different periodontal diseases. A review article.

Tetracyclines have recently been shown to inhibit the activity of some but not all mammalian matrix metalloproteinases believed to mediate periodontal destruction. However, the specificity of this effect, which could have significant therapeutic implications for different periodontal diseases, has not been examined in detail. Doxycycline and 4-de-dimethylaminotetracycline (CMT-1) have been tested in vitro for their ability to inhibit human neutrophil and fibroblast interstitial collagenases and collagenase in human gingival crevicular fluid (GCF). The GCF samples were obtained from systemically healthy and insulin-dependent diabetic adult periodontitis patients and from localized juvenile periodontitis (LJP) patients. The concentrations of these 2 tetracyclines required to inhibit 50% of the collagenase activity (IC50) were found to be 15 to 30 microM for human neutrophil collagenase and for collagenase in GCF of systemically healthy and diabetic adult periodontitis patients. These concentrations approximate the tetracycline levels observed in vivo during treatment with these drugs. In contrast, human fibroblast collagenase and GCF collagenase from LJP patients were both relatively resistant to tetracycline inhibition; the IC50 for doxycycline and CMT-1 for these 2 sources of collagenase were 280 and 500 microM, respectively. Based on these and other findings, we propose the following: 1) that systemic levels of tetracycline may inhibit connective tissue breakdown by inhibiting neutrophil collagenase; 2) that tetracyclines do not inhibit fibroblast-type collagenase, which may help explain their lack of effect on normal connective tissue remodeling; 3) that tetracycline inhibition of collagenases may serve to identify the cellular origin of the enzyme; and 4) that tetracyclines can also prevent the oxidative activation of latent human procollagenases.(ABSTRACT TRUNCATED AT 250 WORDS)

Collagenases↗
PubMed1992

The anticollagenolytic potential of lymecycline in the long-term treatment of reactive arthritis.

OBJECTIVE: We sought to determine the antiinflammatory properties of lymecycline in the long-term treatment of reactive arthritis (ReA). METHODS: Quantitative assay of collagenase activity by densitometry after sodium dodecyl sulfate-polyacrylamide gel electrophoresis. RESULTS: Therapeutic levels of lymecycline do not directly inhibit the activity of human neutrophil interstitial collagenase, but can prevent the oxidative activation of latent human neutrophil collagenase. CONCLUSION: This non-antimicrobial, anticollagenolytic property of lymecycline may contribute to its therapeutic efficacy in the treatment of patients with ReA.

Arthritis, Reactive↗
PubMed1992

Collagenase in synovitis of rheumatoid arthritis.

There are two types of collagenases, products of two distinct genes, called MMP-1 (matrix metalloproteinase 1 or "fibroblast-type collagenase") and MMP-8 ("neutrophil collagenase"). In synovial fluid, MMP-8 is stored as latent proenzyme in polymorphonuclear neutrophils. MMP-8 is activated by hypochlorous acid produced by myeloperoxidase from hydrogen peroxide and chloride ion and by the hydroxyl radical produced in Haber Weiss reaction fed by superoxide produced by, eg, NADPH (reduced nicotinamide adenine dinucleotide) oxidase and xanthine oxidase. In addition to activation upon secretion, oxidatively modified MMP-8 is susceptible to a subsequent proteolytic attack and activation by cathepsin G. The authors suggest that activation of neutrophil-derived MMP-8 involves oxidative, nonproteolytic activation upon secretion and a more slowly progressive proteolytic activation by cathepsin G (or chymases and tryptases), and that these oxidative and proteolytic activation mechanisms act in concert. In contrast to MMP-8, MMP-1 is synthesized de novo and secreted immediately after synthesis by fibroblasts, macrophages, and some epithelial cells. Human rheumatoid synovial tissue contains mainly fibroblast-type MMP-1 collagenase as assessed by collagenase extracted from synovial tissue and by MMP-1 and MMP-8 immunostaining. It is suggested that in vivo, MMP-1 in synovitis tissue is activated by a plasminogen activator/plasminogen/prostromelysin (alternatively tryptases)/proMMP-1 cascade. In conclusion, MMP-8 and MMP-1 show type-specific compartmentalization and modes of activation in rheumatoid synovial fluid and tissue.

Arthritis, Rheumatoid↗
PubMed1992

Tetracycline inhibition identifies the cellular origin of interstitial collagenases in human periodontal diseases in vivo.

Mammalian interstitial collagenases (E.C.3.4.24.7) are considered as key initiators of collagen degradation in periodontal diseases. However, the cellular sources of collagenases present in gingival crevicular fluid have not been completely clarified. Resident fibroblasts and epithelial cells as well as infiltrating neutrophils and monocyte/macrophages are potential sources of the enzymes. We have recently found significant differences in tetracycline inhibition between human neutrophil and fibroblast interstitial collagenases. To address the cellular source of collagenase present in gingival crevicular fluid in 2 distinct periodontal diseases, we studied the tetracycline inhibition of collagenase in gingival crevicular fluid of patients with localized juvenile periodontitis and adult periodontitis. Gingival crevicular fluid samples were collected from deep (greater than 5 mm) periodontal pockets and assayed for collagenase in the presence of 0-1000 microM doxycycline as well as a chemically modified tetracycline devoid of antimicrobial activity (4-de-dimethylaminotetracycline). The drug concentration required to inhibit 50% of collagenase activity (IC50) in localized juvenile periodontitis gingival crevicular fluid was 280 microM for doxycycline and 470 microM for 4-de-dimethylaminotetracycline. Significantly lower values, 10-20 microM, were obtained for collagenase in gingival crevicular fluid of patients with adult periodontitis. We propose that systemic tetracycline levels are efficient inhibitors of collagenase in gingival crevicular fluid in affected sites of patients with adult periodontitis but not of patients with localized juvenile periodontitis and that the fibroblast type interstitial collagenase is the predominant collagenase type in gingival crevicular fluid in affected sites of patients with localized juvenile periodontitis and the neutrophil collagenase in adult periodontitis gingival crevicular fluid.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Cellular source and tetracycline-inhibition of gingival crevicular fluid collagenase of patients with labile diabetes mellitus.

Accelerated periodontal tissue destruction in patients with labile insulin-dependent diabetes mellitus (DM) and localized juvenile periodontitis (LJP) has been suggested to be related to functional abnormalities of neutrophils. We have recently found that collagenase in gingival crevicular fluid (GCF) of adult periodontitis patients is primarily derived from neutrophils and that neutrophil collagenase activity is more sensitive to inhibition by tetracyclines than collagenase produced by fibroblasts. This study is to characterize the cellular sources, activation and inhibition of collagenase in GCF of DM patients and to compare it with collagenase in LJP GCF. We found differences which may have therapeutic implications. Specific doxycycline inhibition tests revealed that GCF collagenase in DM is derived from neutrophils, whereas the enzyme in LJP originates primarily from fibroblasts. Oxidant, sodium hypochlorite, activated efficiently GCF collagenase of DM but not LJP patients. In contrast, plasmin activated LJP GCF collagenase but not that of DM patients. In GCF of DM patients 50-60% of collagenase existed in an active form, whereas in LJP GCF, the enzyme was almost completely in a latent form. The results suggest that collagenase in GCF of periodontitis patients with labile DM is primarily derived from neutrophils and that tetracycline therapy may be an effective adjunct in treatment aimed at controlling the periodontal breakdown in these patients. On the other hand, in LJP the anti-collagenase property of tetracyclines may be less important for control of periodontal tissue destruction because of the tetracycline-resistance of fibroblast collagenase.

Aggressive Periodontitis↗
PubMed1992

Relationship of collagenase and cathepsin G activity in gingival crevicular fluid.

Human neutrophil cathepsin G has been identified as a potent proteolytic activator of latent human neutrophil collagenase in vitro. In order to examine the role of cathepsin G in the activation mechanism of latent human neutrophil collagenase in vivo, gingival crevicular fluid was collected from periodontal pockets of patients with adult periodontitis and the relationship of cathepsin G to the proportion of endogenously active collagenase and total collagenase activity was determined. The changes in these parameters were monitored before and after periodontal therapy and compared to control values obtained for periodontal sites without clinical signs of inflammation or increased pocket depth. A significant decrease in cathepsin G and collagenase activity in gingival crevicular fluid collected from initially deep periodontal pockets was observed in response to scaling and root planing (P less than 0.025, Wilcoxon signed rank test). Also the proportion of endogenously active collagenase decreased (P less than 0.05). There was a significant correlation of cathepsin G and total collagenase activity. However, no correlation of cathepsin G activity and endogenously active collagenase was observed. The results indicate the existence of several distinct activation pathways for latent human neutrophil collagenase in vivo and suggest that, apart from cathepsin G, other proteolytic activation cascades and/or non-proteolytic activation pathways participate in the activation of latent human neutrophil collagenase in vivo.

Cathepsin G↗
PubMed1992

Specificity of the anticollagenase action of tetracyclines: relevance to their anti-inflammatory potential.

The concentrations of doxycycline and 4-de-dimethylaminotetracycline required to inhibit 50% of collagenase activity were found to be 15 to 30 microM for human neutrophil and gingival crevicular fluid collagenases. Fibroblast collagenase was relatively resistant to inhibition by tetracyclines; the 50% inhibitory concentrations of doxycycline and 4-de-dimethylaminotetracycline were 280 and 510 microM, respectively.

Anti-Inflammatory Agents↗
PubMed1992

Identification of proteases from periodontopathogenic bacteria as activators of latent human neutrophil and fibroblast-type interstitial collagenases.

Activation of latent human fibroblast-type and neutrophil interstitial procollagenases as well as degradation of native type I collagen by supra- and subgingival dental plaque extracts, an 80-kDa trypsinlike protease from Porphyromas gingivalis (ATCC 33277), a 95-kDa chymotrypsinlike protease from Treponema denticola (ATCC 29522), and selected bacterial species commonly isolated in periodontitis was studied. The bacteria included were Prevotella intermedia (ATCC 25261), Prevotella buccae (ES 57), Prevotella oris (ATCC 33573), Porphyromonas endodontalis (ES 54b), Actinobacillus actinomycetemcomitans (ATCC 295222), Fusobacterium nucleatum (ATCC 10953), Mitsuokella dentalis (DSM 3688), and Streptococcus mitis (ATCC 15909). None of the bacteria activated latent procollagenases; however, both sub- and supragingival dental plaque extracts (neutral salt extraction) and proteases isolated from cell extracts from potentially periodontopathogenic bacteria P. gingivalis and T. denticola were found to activate latent human fibroblast-type and neutrophil interstitial procollagenases. The fibroblast-type interstitial collagenase was more efficiently activated by bacterial proteases than the neutrophil counterpart, which instead preferred nonproteolytic activation by the oxidative agent hypochlorous acid. The proteases were not able to convert collagenase tissue inhibitor of metalloproteinase (TIMP-1) complexes into active form or to change the ability of TIMP-1 to inhibit interstitial collagenase. None of the studied bacteria, proteases from P. gingivalis and T. denticola, or extracts of supra- and subgingival dental plaque showed any significant collagenolytic activity. However, the proteases degraded native and denatured collagen fragments after cleavage by interstitial collagenase and gelatinase. Our results indicate that proteases from periodontopathogenic bacteria can act as direct proteolytic activators of human procollagenases and degrade collagen fragments. Thus, in concert with host enzymes the bacterial proteases may participate in periodontal tissue destruction.

Collagenases↗
PubMed1992

Host modulation with tetracyclines and their chemically modified analogues.

Recent studies have suggested the use of drugs to modulate host response as a new approach in periodontal therapy. In this regard, the tetracycline antibiotics have been found to inhibit host-derived collagenases and other matrix metalloproteinases by a mechanism independent of the antimicrobial activity of these drugs; this effect may suppress connective tissue breakdown during periodontal disease and during a variety of medical disorders including (but not limited to) noninfected corneal ulcers, serious (sometimes life-threatening) skin-blistering diseases, rheumatoid arthritis and osteoarthritis, systemically--as well as locally--induced bone loss, and perhaps even tumor-induced angiogenesis. Two therapeutic strategies based on the host-modulating properties of tetracyclines are currently being developed: 1) the use of low-dose doxycycline (the most potent anticollagenase of commercially available tetracyclines) formulations, which do not appear to result in tetracycline side effects such as the emergence of antibiotic-resistant microorganisms; and 2) the production of a family of chemically modified tetracyclines that have lost their antimicrobial activity, but have retained their anticollagenase activity. A description of several of these compounds and a discussion of their efficacy in inhibiting collagenases in vitro and reducing tissue destruction in several animal models of periodontal and medical diseases is presented.

Alveolar Bone Loss↗
PubMed1992

Tetracycline inhibition identifies the cellular sources of collagenase in gingival crevicular fluid in different forms of periodontal diseases.

Tetracyclines have recently been shown to inhibit the activity of mammalian matrix metalloproteinases, i.e. type I collagenase (MMP-1) and type IV collagenase/gelatinase (MMP-2). The specificity of this effect, however, has not been examined in detail. In the present study, doxycycline (a clinically widely used commercial tetracycline) and 4-de-dimethylaminotetracycline (CMT-1, a chemically modified non-antimicrobial tetracycline) were tested, at a wide range of concentrations, for their ability to inhibit human neutrophil and fibroblast interstitial collagenases, which are distinct gene products, as well as collagenase in human gingival crevicular fluid (an inflammatory exudate in periodontal lesions) obtained from adult, juvenile and diabetic adult periodontitis patients. The concentrations of these two tetracyclines, required to inhibit 50% of the collagenase activity (IC50), were found to be 15-30 microM for purified human neutrophil collagenase as well as collagenase in gingival crevicular fluid of adult periodontitis patients and diabetic adult periodontitis patients, thus approximating in vivo therapeutic tetracycline levels. In contrast, the fibroblast collagenase and collagenase in gingival crevicular fluid of patients with juvenile periodontitis were relatively resistant to tetracycline inhibition: the IC50 for doxycycline and CMT-1 were 280 and 500 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗