Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Interleukin-1 beta (IL-1 beta) may be related to the pathological processes associated with periodontitis, primarily due to its ability to induce collagenase, increase neutrophil chemotaxis, and stimulate bone resorption. This study was designed to histologically quantitate IL-1 beta positive cells from various histologic fields in untreated gingivitis/early periodontitis (G/EP) versus moderate/severe periodontitis (M/SP) gingival tissues, and associate these with collagen loss. Two gingival biopsies from 8 patients were collected, one from a G/EP site and one from a M/SP site. Mouse monoclonal antibodies in combination with an avidin-biotin-peroxidase system were used to stain for IL-1 beta, while the van Gieson method was used to stain for collagen in serial sections. Collagen loss in G/EP (35%) and M/SP (52%) fields was consistent with gingivitis and periodontitis, respectively. IL-1 beta positive cells in combined coronal/sulcular (Co/Su) and apical/sulcular (Ap/Su) fields (nearest the bacterial insult) were significantly more numerous compared to combined coronal/middle (Co/Mi) and apical/middle (Ap/Mi) fields (p < 0.05). While numbers and percentages of IL-1 beta positive cells were generally higher in M/SP biopsies, differences were not significant. Further, there was no correlation between the number of IL-1 beta positive cells and percent collagen loss. However, a significant correlation between IL-1 beta positive cells and corresponding gingival crevicular fluid IL-1 beta concentrations was noted (r = 0.65, p = 0.01). Through the use of immunohistochemistry, this study demonstrated that the presence of IL-1 beta + cells does not appear to have a direct association with collagen loss.
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PMID:Histological evaluation of interleukin-1 beta and collagen in gingival tissue from untreated adult periodontitis. 750 86

Chronic periodontitis is characterized by dense infiltrations of B and T lymphocytes within the gingival connective tissue. Distinct anaerobic gram-negative bacteria as well as autoimmunity to collagen have been reported to play a role in the etiology and the pathogenesis of this disease. Here we describe the cloning and characterization of CD4+ and CD8+ T lymphocytes isolated from inflamed gingival tissue obtained from four patients with chronic periodontitis. Clones were raised with phytohemagglutinin and interleukin-2 and tested for proliferation in response to whole-cell antigens of Porphyromonas gingivalis, Prevotella intermedia, Actinobacillus actinomycetemcomitans, human collagen type I, and two bacterial heat shock proteins. CD4+ T-cell clones reactive with collagen type I were obtained from all four patients. Eighty percent of these clones had phenotypes resembling the mouse type 2 T helper (Th) phenotype, i.e., they produced high levels of interleukin-4 and low levels of gamma interferon. No collagen-type-I-reactive CD8+ clones were obtained. Bacterial-antigen-reactive CD4+ and/or CD8+ T-cell clones were also obtained from each patient, and the majority of the clones showed a Th0-like cytokine pattern and produced equal amounts of interleukin-4 and gamma interferon. Although most clones were reactive with P. intermedia, it seems that the immune response is not strictly directed against this particular microorganism, as clones reactive with one of the other bacteria were also obtained from two patients. We propose that collagen-specific CD4+ Th2-like T cells contribute to the chronicity of periodontitis but that their modes of activation might be controlled by Th0-like T cells specific for periodontitis-associated bacteria.
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PMID:Cloning, characterization, and antigen specificity of T-lymphocyte subsets extracted from gingival tissue of chronic adult periodontitis patients. 753 6

This investigation was undertaken to evaluate cross-linked human type I collagen, with and without added metronidazole, when used as a barrier membrane in the guided tissue regeneration (GTR) principle of treatment for periodontal disease. 16 patients suffering from moderate to severe periodontitis with 78 bilaterally matched periodontal defects underwent similar contralateral surgical flap procedures after preliminary scaling, polishing and oral hygiene instruction. At the experimental sites, which were selected at random, the flap was closed over metronidazole impregnated collagen as a GTR membrane, the contralateral sites receiving a plain collagen barrier as control. The plaque index (PLI), gingival index (GI), bleeding index (BI), probing pocket depth (PPD) and probing attachment level (PAL) were recorded at baseline, 6, 12 and 26 weeks post-operatively. The bony defects were classified and furcation involvement noted. The clinical parameters were recorded by an examiner, other than the surgeon, who had been previously assessed for accurate reproducibility of measurements and was unaware of the experimental sites. PPD and PAL were measured with a constant pressure probe, localised by a soft stent. Post-operative discomfort was evaluated by means of a questionnaire. PLI, GI and BI were significantly improved compared to baseline for both test and control sites at 6, 12 and 26 weeks post surgery (p < 0.001) but there was no significant difference between these sites (p > 0.05). There was a reduction in PPD at 6 weeks which was significant at 12 and 26 weeks post-operatively (p < 0.001) for both test and control sites, but no difference between these sites was evident (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparative clinical study: the use of human type I collagen with and without the addition of metronidazole in the GTR method of treatment of periodontal disease. 756 Feb 38

Dental plaque is the major aetiological factor in periodontal diseases and contains several proteolytic enzymes. The origin of these proteinases is, however, poorly studied. This study was undertaken to characterize collagenase present in dental plaque of adult periodontitis patients. Vertebrate-type rather than bacterial-derived collagenase activity was detected in extracts of both supra- and subgingival dental plaque extracts of adult periodontitis patients. Dental plaque collagenase was found to exist predominantly in autoactive form. Dental plaque collagenase from periodontally healthy individuals existed in latent from. Latent dental plaque collagenase from periodontitis lesions could be activated by a 95 kD chymotrypsin-like proteinase from Treponema denticola and human leukocyte cathepsin G but not by human plasmin. Incubation of purified latent leukocyte collagenase with whole cells of Fusobacterium nucleatum, Eubacterium saburreum, Prevotella buccae and Porphyromonas gingivalis, however, did not result to the activation of the enzyme. Doxycycline in vitro inhibited dental plaque collagenase with an IC50-value of 20 microM. Dental plaque collagenase degraded more efficiently type I and II collagens than type III collagen. Western-blot analysis with specific anti-human neutrophil collagenase-antibody revealed that both in supra- and subgingival dental plaque extracts dental plaque collagenase had undergone proteolytic conversion from an 80 kD proform to a 58 kD active form which is associated with catalytic autoactivity as measured by functional collagenase assay. This reflects proteolytic activation of leukocyte collagenase in dental plaque probably by other proteases derived from potent periodontopathogenic bacteria such as T. denticola or other PMN proteases such as cathepsin G.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cellular source, activation and inhibition of dental plaque collagenase. 759 2

Periodontitis is characterized by asymptomatic periodic collagen degradation, which is accompanied by the formation of granulation tissue induced by bacteria. The lesions sometimes contain micro-organisms and/or micro-abscesses that are of unknown significance. The aim of this study was to determine whether bacteria in a sterile granulation tissue could enhance its collagenolytic capacity. The formation of granulation tissue was induced by implanting a cellulose sponge in the subcutaneous tissue in the back of the rat. Bacteria were injected every other day into the sponge from day 8 to day 18. The cell-dependent degradation of a homologous 3H-collagen powder enveloped in the sponge was measured by the radioactivity of the urine excreted 8-18 days after the implantation. The injections increased the excretion of radioactivity by about 40% compared with the controls (n = 8, p < or = 0.005), but caused no clinical signs of acute infection or inflammation. On day 18, 2 days after the last injection of bacteria, no bacteria or increased cell infiltration were observed in the granulation tissue. The appearance of the latter could not be distinguished from that of the control tissues injected with buffer alone. It seems reasonable to assume that the increased collagen degradation results from enhanced activity of phagocytes, which may also be related to an increased release of tissue-destructive proteases and free oxygen radicals into the extracellular space. In conclusion, brief recurrent episodes of bacteria in granulation tissue can increase its collagen degrading-capacity. The latter may be due to augmented cell activity in the tissue. This response seems to have some features comparable to the pathogenesis of episodic periodontitis, e.g., by mimicking the collagen degradation.
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PMID:Increased collagen degradation by experimentally-induced granulation tissue inoculated with bacteria. 762 34

Tetracycline hydrochloride treatment of cementum and dentin surfaces derived from human teeth not affected by periodontitis resulted in the removal of the smear layer and uncovered a fibrillar collagen substrate. In cementum specimens, the amount of exposure of the organic matrix appeared to be more related to morphologic structure of the cementum and mechanical instrumentation of the root surface rather than to concentration and time of application of tetracycline solution. Time-dependent changes were observed in dentin surfaces, the intertubular "matted" collagen matrix being evident only in the 4-minute specimens.
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PMID:Nondiseased cementum and dentin root surface following tetracycline hydrochloride conditioning: SEM study of the effects of solution concentration and application time. 775 Nov 12

We previously reported that low-dose doxycycline (DOXY) therapy reduces host-derived collagenase activity in gingival tissue of adult periodontitis (AP) patients. However, it was not clear whether this in vivo effect was direct or indirect. In the present study, inflamed human gingival tissue, obtained from AP patients during periodontal surgery, was extracted and the extracts partially purified by (NH4)2SO4 precipitation. The extracts were then analyzed for collagenase activity using SDS-PAGE/fluorography/laser densitometry, and for gelatinase activity using type I gelatin zymography as well as a new quantitative assay using biotinylated type I gelatin as substrate. DOXY was added to the incubation mixture at a final concentration of 0-1000 microM. The concentration of DOXY required to inhibit 50% of the gingival tissue collagenase (IC50) was found to be 16-18 microM in the presence or absence of 1.2 mM APMA (an optimal organomercurial activator of latent procollagenases); this IC50 for DOXY was similar to that exhibited for collagenase or matrix metalloproteinase (MMP)-8 from polymorphonuclear leukocytes (PMNs) and from gingival crevicular fluid (GCF) of AP patients. Of interest, Porphyromonas gingivalis collagenase was also inhibited by similar DOXY levels (IC50 = 15 microM), however the collagenase activity observed in the gingival tissue extracts was found to be of mammalian not bacterial origin based on the production of the specific alpha A (3/4) and alpha B (1/4) collagen degradation fragments. In contrast, the inhibition of collagenase purified from culture media of human gingival fibroblasts (MMP-1) required much greater DOXY levels (IC50 = 280 microM). The predominant molecular forms of gelatinolytic activity presented in the AP patients gingival tissue extracts were found to closely correspond to the 92 kD PMN-type gelatinase (MMP-9) although small quantities of 72 kD fibroblast-type gelatinase (MMP-2), and some other low molecular weight gelatinases, were also detected. The IC50 of DOXY versus gingival tissue gelatinolytic activity was estimated at 30-50 microM measure using either type I gelatin zymography or the biotinylated type I gelatin assay. We conclude that MMPS in inflamed gingival tissue of AP patients, like those in GCF, originate primarily from infiltrating PMNs rather than resident gingival cells (fibroblasts and epithelial cells) or monocyte/macrophages, and that their pathologically-elevated tissue-degrading activities can be directly inhibited by pharmacologic levels of doxycycline.
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PMID:Doxycycline inhibits neutrophil (PMN)-type matrix metalloproteinases in human adult periodontitis gingiva. 777 65

A redox dye, methylene blue, was compared with subgingival root surface debridement and sterile water in the treatment of adult periodontitis. Plaque and gingival indices, bleeding on probing, and microbiological samples were obtained at baseline, and at 1, 4, 8 and 12 weeks following treatment. All subjects had matched pockets in each of the 4 quadrants, of 5 mm or more. One treatment consisted of 0.1% methylene blue gel irrigated professionally at 0, 1 and 4 weeks, and by subjects at days in between up to 4 weeks, at chosen sites within a randomly selected quadrant (split-mouth design). A 2nd treatment was sterile water irrigation as above. A 3rd quadrant received subgingival debridement, and sites in the 4th received methylene blue incorporated into a slow-release device of a biodegradable collagen alginate vicryl composite. All sites showed improvements in clinical and microbiological parameters. However, no statistically significant differences between treatment types were found for clinical measurements. Although plaque index tended to increase after week 1, gingival index was reduced, as was the papilla bleeding index. Probing depth reductions were approximately 1.2 mm for all treatments. Microbiological variables showed an increase in cocci and a decrease in motile organisms for all groups, the latter reaching statistical significance for subgingival debridement. The reductions in spirochaetes were significant for subgingival debridement and methylene blue by slow-release. Culture demonstrated an increase in the aerobe:anaerobe ratio for all groups, which was statistically significant initially (weeks 1 and 4) for subgingival debridement. Methylene blue was also effective statistically in improving this ratio, both by irrigation and slow-release (week 4). Methylene blue also significantly reduced the numbers of black-pigmented anaerobes during the trial period, both by irrigation and slow-release, which sterile water and subgingival debridement failed to do. No serious adverse experiences were seen, however, significantly greater morbidity was associated with subgingival debridement. These results clearly demonstrate that in altering the microflora to one that is more compatible with periodontal health, methylene blue treatment is comparable, or even better, than the currently standard treatment of subgingival debridement, and is better tolerated.
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PMID:Evaluation of the efficacy of a redox agent in the treatment of chronic periodontitis. 785 14

We investigated the expression of membrane alkaline phosphatase (ALP) activity on fibroblasts in inflamed gingiva from 7 patients with adult periodontitis. ALP activity was ultrahistochemically detected by a cerium-based capture method. The degree of ALP activity was estimated by morphometric analysis of the percentage of the perimeter on which ALP reaction product was deposited. Fibroblasts in the non-inflammatory connective tissue were surrounded by bundles of collagen fibrils, and the majority of these fibroblasts showed ALP-negative or weakly ALP-positive reaction. By contrast, fibroblasts in the inflammatory connective tissue were either surrounded by a non-collagenous substance or in contact with inflammatory cells, and the majority of these fibroblasts showed a strong ALP-positive reaction. These results suggest that the expression of membrane ALP activity on gingival fibroblasts is induced by microenvironmental changes associated with the loss of contact between the cells and the extracellular collagenous matrix during inflammatory reactions.
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PMID:Expression of membrane alkaline phosphatase activity on gingival fibroblasts in chronic inflammatory periodontal disease. 793 19

Cellular and biochemical observations were made of fibroblasts harvested from ligature-induced periodontitis and treated gingivitis areas in four adult female cynomolgus monkeys (Macaca fascicularis) to define the changes that occur in the early periodontitis lesion. Compared with fibroblasts from the treated sites, fibroblasts from the diseased areas had a significantly higher rate of proliferation, produced about two-thirds the amount of total protein and collagen, and failed to respond to TGF-beta, which normally stimulates extracellular matrix formation in mesenchymal cells. The diseased cells were also deficient in the activity of poly(ADP-ribose) synthetase, an enzyme involved in the repair of DNA breaks such as occur from the insults of superoxide and other active radicals present in inflamed areas. Although the precise nature of these biochemical defects is not fully elucidated, they may have an important bearing on chronic periodontitis cases with a "downhill" course.
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PMID:Alterations of fibroblast metabolism in early ligature-induced periodontitis in the cynomolgus monkey. 796 54


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