bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of intergeneric coaggregation among oral bacteria by cetylpyridinium chloride, chlorhexidine digluconate and octenidine dihydrochloride
Authors: Smith Richard N. , Andersen Roxanna N. , Kolenbrander Paul E.
Published: July 2006

The potential inhibitory effect of chlorhexidine digluconate on the intergeneric coaggregation of 11 pairs of Gram‐positive organisms was compared to its ability to inhibit coaggregations of 14 pairs comprised of both a Gram‐positive and a Gram‐negative cell type. Dramatic differences in the inhibitory effectiveness of the antimicrobial compound on the two kinds of coaggregating pairs were found. Gram‐positive pairs were not inhibited at a concentration of 0.25%, whereas the coaggregations involving a Gram‐negative partner were usually completely blocked at concentrations as low as 0.01%. Similar effects to chlorhexidine digluconate were found with octenidine dihydrochloride and cetylpyridinium chloride, while sodium dodecylsulfate was inhibitory only at 10‐ to 50‐fold higher concentrations. These results suggest that chlorhexidine digluconate, octenidine dihydrochloride, and cetylpyridinium chloride may be effective inhibitors of later microbial colonizers of dental plaque but may not disturb a normal healthy indigenous flora.
Multicenter evaluation of tetracycline fiber therapy. III. Microbiological response
Authors: Goodson J. M. , Tanner A. , McArdle S. , Dix K. , Watanabe S. M.
Published: July 2006

In a multicenter study of the effects of tetracycline (TC) fiber therapy, subgingival plaque samples were tested for 6 probable periodontal pathogens by DNA probe analysis. Levels of Actinobacillus actinomycetemcomitans, Eikenella corrodens, Fusobacterium nucleatum, Porphyromonas (Bacteroides) gingivalis, Prevotella intermedia (Bacteroides intermedius), and Wolinella recta were quantitatively determined in samples taken at baseline, and immediately after TC fiber removal, control fiber removal, and scaling and root planing. At untreated sites, samples were taken at baseline and 10 d later. Specificity of the DNA probe method was evaluated by testing the hybridization to 83 reference cultures. Interaction of the F. nucleatum probe with Fusobacterium periodonticum, and of the W. recta probe with Wolinella curva were the only cross‐hybridizations noted. Species were detected at an average sensitivity of 2.9 × 104 organisms per sample. Approximately 70% of sites were initially infected with P. gingivalis and F. nucleatum; 50% with P. intermedia and E. corrodens; infections with W. recta and A. actinomycetemcomitans were less common (36% and 11% respectively). The average numbers of organisms found in plaque samples were highest for F. nucleatum, P. gingivalis, and P. intermedia (ca. 106). E. corrodens, W. recta, and A. actinomycetemcomitans occurred at 10‐fold lower levels. Bacterial numbers and proportions of species in subgingival sites from the five centers did not differ appreciably. Both TC fiber therapy and scaling decreased the number of sites infected with all the monitored species. The bacterial composition at untreated sites and at sites where control fibers were placed was not significantly altered. The percentage reduction of the number of sites with delectable infection varied with each species: from 86% with W. recta to approximately 40% with P. gingivalis. Significant reduction of pocket depth and bleeding occurred at TC fiber‐treated sites infected with each of the species. Significant attachment level gain occurred only at sites initially infected with P. gingivalis and treated with TC fibers.
Patterns of cytokeratin expression in human gingival epithelia
Authors: Mackenzie I. C. , Rittman G. , Gao Z. , Leigh I. , Lane E. B.
Published: July 2006

Specimens of human gingiva were collected from teenage and adult subjects and frozen sections were stained with an extensive panel of monoclonal antibodies with defined specificities for individual cytokeratins. The results indicated different and distinctive patterns of keratin expression by the oral gingival, oral sulcular and the junctional epithelia. It was observed that epithelium with staining characteristics of sulcular epithelium extended over the gingival crest onto the oral surface of the gingiva. Junctional epithelium showed the unusual pattern of co‐expression of keratins typical of the stratifying and of the simple epithelial phenotypes. The patterns of gingival keratin expression are compared with those of other mucosal epithelia. The findings are discussed in relation to mechanisms that may determine or influence the junctional epithelial phenotype.
Collagenase activity in recurrent periodontitis: relationship to disease progression and doxycycline therapy
Authors: Lee W. , Aitken S. , Kulkarni G. , Birek P. , Overall C. M. , Sodek J. , McCulloch C. A. G.
Published: July 2006

Previous reports have suggested that active progression of periodontitis may be correlated with increased collagenolytic activity, and that improved clinical conditions after tetracycline treatment may be explained by inhibition of host collagenase. Eighty‐two patients with a recent history of periodontal abscesses and/or loss of gingival attachment level (GAL) despite active periodontal therapy were enrolled in a double‐blind, randomized, placebo‐controlled trial. Clinical measurements, sampling of gingival crevicular fluid (GCF) and sub‐gingival scaling were performed every 2 months. If any site exhibited > 2 mm loss of GAL or a periodontal abscess, patients were administered either 100 mg doxycycline per day for 3 weeks or placebo. During 12 months of monitoring, 55 patients exhibited recurrent active disease and were then randomly assigned to either the doxycycline (n = 30) or placebo (n = 25) groups. Analysis of active collagenase and latent collagenase in GCF samples were determined by functional assays and quantitated after SDS‐PAGE and fluorography. Collagenase activities were assayed at sites exhibiting active destruction (study site), at sites with pocket depth comparable to the study site but without active destruction, and at healthy sites. Clinical measurements of GAL and collagenase activity were made at intervals between l wk and 7 months after completion of the drug regime. Within 7 months, 15 out of 19 patients on placebo exhibited recurrent disease compared to 13 out of 29 patients on doxycycline. Collagenase activity exhibited large variations among patients and was analyzed as presence or absence of active collagenase with a logistic model. The frequency of study sites with active collagenase was 20% higher than that of comparable sites and was 60% higher than control sites. Collagenase activity remained elevated throughout the experimental period in spile of clinical remission from active destructive disease. There was no detectable difference between placebo and doxycycline groups of collagenase activity in vivo during or after the administration of the drug. Separate tests of reproducibility demonstrated that less than 8% of the total variability of the results was due to assay error, diurnal Variation or sampling errors. These data indicate that analysis of collagenase activity could provide an effective diagnostic method to detect the presence of progressive periodontal lesions.
Immunolocalization of proteins specific for adhaerens junctions in human gingival epithelial cells grown on differently processed titanium surfaces
Authors: Hormia M. , Könönen M. , Kivilahti J. , Virtanen I.
Published: July 2006

The localization of desmoplakins 1 and 2 (DP 1&2), components of desmosomes, vinculin, and actin, was studied in gingival epithelial cells grown on cell culture glass and on titanium plates with various surface topography. The results showed that epithelial cells attached and spread more readily on smooth than on rough, sandblasted titanium surfaces. Moreover, the cells appeared to develop more granular DP 1&2 immunoreactivity at their ventral surfaces when grown on smooth or etched titanium as compared to glass. In cells grown on sandblasted titanium surfaces, DP l&2‐specific immunoreactivity was primarily located at cell‐cell contacts. Cells grown on smooth titanium surfaces harbored a fine network of actin filaments with apparent cell‐to‐cell organization. Vinculin was confined to cell‐cell contact areas. No vinculin‐containing focal adhesions could be detected, suggesting that the cells adhere either by means of close contacts, extracellular matrix contacts, or by means of hemidesmosomes. The findings suggest that smooth or finely grooved titanium surfaces could be optimal in maintaining the adhesion and specialized phenotype of gingival epithelial cells.
Inhibition of alveolar bone loss in beagles with the NSAID naproxen
Authors: Howell T. H. , Jeffcoat M. K. , Goldhaber P. , Reddy M. S. , Kaplan M. L. , Johnson H. G. , Hall C. M. , Williams R. C.
Published: July 2006

The non‐steroidal anti‐inflammatory drug(NSAID) naproxen was studied in 11 beagle dogs over a 13‐month period to determine its effect on the progression of periodontitis. Following a 6‐month pretreatment period, 5 dogs received naproxen daily at a dosage of 2.0 mg/kg for 1 month, then 0.2 mg/kg for 6 months. Six control dogs received a gelatin capsule daily as placebo. Standardized radiographs were used to measure the rate of bone loss during the pretreatment and treatment periods. In the control dogs, the rate of bone loss was seen to increase during the treatment period although the increase was not statistically significant. In dogs treated daily with naproxen, the rate of bone loss in the treatment period was significantly less at 4 months of treatment; however, at 7 months the difference, though lower than pretreatment rate, was not significant. When the percent change in rate of bone loss during the overall 7‐month treatment period was compared with pretreatment rate, the control dogs demonstrated a 38% increase in rate of bone loss during the treatment period contrasting with a 61% decrease in bone loss rate in naproxen‐treated dogs. The data indicate that the non‐steroidal anti‐inflammatory drug naproxen can significantly inhibit alveolar bone loss in beagles. At 4 months of treatment the rate of bone loss in the naproxen‐treated dogs was significantly less than pretreatment, but at 7 months of treatment the rate was no longer statistically significantly less than baseline. This probably reflects a dose response to naproxen treatment for, after 30 days of the treatment period, the naproxen dosage was reduced 10‐fold due to tolerance by the beagle.
Expression of interleukin‐2 receptor and HLA‐DR on lymphocyte subsets of gingival crevicular fluid in patients with periodontitis
Authors: Takeuchi Yoshiharu , Yoshie Hiromasa , Hara Kohji
Published: July 2006

Expression of interleukin‐2 receptor (IL2R) and HLA‐DR on lymphocytes of gingival crevicular fluid (GCF) was examined by two‐color flow cytometric analysis. GCF from 15 patients with periodontitis was collected by crevicular washing. Mononuclear cells were isolated by Ficoll‐paque gradient centrifugation from inflamed gingival tissue (GT) and peripheral blood (PB) sampled from each of the 15 patients. Lymphocyte subsets were detected by using monoclonal antibodies (mAb) of Leu 12 (CD19), Leu 4 (CD3), Leu 3a (CD4) and Leu 2a (CD8) directed to B cells, T cells, helper/inducer T cells (Th) and suppressor/ cytotoxic T cells (Ts), respectively. Anti‐IL2R (CD25) and anti‐HLA‐DR were used as lymphocyte activation markers. IL2R‐ or HLA‐DR‐positive fractions in Th, Ts and B cells were calculated. Percentage of IL2R‐positive fraction in Th (IL2R+ Th) of GCF (34.0%) was significantly higher than those of GT (18.4%) and PB (13.7%). IL2R‐positive fraction in B cells (IL2R+B) of GCF was the highest among the three groups (23.9% in GCF, 12.5% in GT, 6.3% in PB). Ts did not express IL2R regardless of the origin of the samples. Compared with PB and GT, GCF showed significantly higher HLA‐DR expression on Th and Ts in GCF (PB: 8.7% and 27.1%; GT: 27.9% and 50.3%; GCF: 44.7% and 65.3%). These results suggest that lymphocytes in GCF were highly activated and are related to the local host immune response in periodontitis.
Black‐pigmenting Gram‐negative bacteria in periodontal disease. I. Topographic distribution in the human dentition*
Authors: Mombelli Andrea , McNabb Hal , Lang Niklaus P.
Published: July 2006

The purpose of this study was to determine the distribution of black‐pigmenting Gram‐negative bacteria in the dentition of periodontitis patients and to examine differences in the microbial composition of samples taken from a series of adjacent sites. Separate subgingival samples were taken from the mesial, buccal, distal and oral aspects of every tooth in 10 subjects. Thus, a total of 927 sites, 84 to 102 per patient, were scored clinically and sampled microbiologically. P. intermedia and P. melaninogenica were found in all subjects, P. gingivalis was found in 7. The organisms tended to be distributed unevenly, giving the impression of clusters of positive samples in certain areas of the dentition. 77% of all samples positive for P. gingivalis were also P. intermedia‐positive. Premolars had lower frequencies and mean proportions of P. gingivalis than incisors and molars. In the premolar and molar region, frequencies and mean proportions of P. gingivalis increased with more posterior location. While frequencies indicated a similar topographic distribution of P. intermedia the mean proportions of this organism were more consistent at different locations. Based on a logistic regression model, it was estimated that the probability of detecting P. gingivalis was 34 times higher in any site which had at least 1 P. gingivalis‐positive neighboring site. For P. intermedia any site with at least 1 P. intermedia‐positive neighboring site had a chance 2.4 times higher of harboring the organism as well. The highest chance of detecting P. gingivalis and P. intermedia existed in deep, oral pockets of molars, which bled upon sampling.
Interleukin‐6 production by human gingival fibroblasts
Authors: Bartold P. Mark , Haynes David R.
Published: July 2006

The ability of human gingival fibroblasts to synthesize interleukin‐6 (IL‐6) was studied using in vitro and immunohistochemical techniques. Culture supernatants of human gingival fibroblasts contained significant quantities of IL‐6 activity which could be stimulated by fetal calf serum, recombinant interleukin‐1β and lipopolysaccharide. The activity in the supernatants was specifically attributed to IL‐6 since up to 97% of the activity could be inhibited by an anti‐IL‐6 antibody. Immunohistochemical studies on low‐density human gingival fibroblast cullures indicated that the cells were associated with material reactive to the anti‐IL‐6 antibody. This localization was seen on the cell surface and in the cytoplasm of the cells. Immunoreactivity towards IL‐6 was also noted in sections of human gingivae. Moderate staining was seen in the connective tissues and lower portions of the gingival epithelium, while intense staining was seen at foci of inflammation. The identification of IL‐6 with human gingival tissues and cells implicates this lymphokine in the molecular events associated with the inflammatory periodontal diseases.
Prevalence and natural history of periodontal disease in Scotland – The mediaeval period (900–1600 A. D.)
Authors: Kerr N. W.
Published: July 2006

The periodontal status of a Scottish mediaeval population was studied. No individual over the age of 11 years had an entirely healthy periodontium. While gingivitis was widespread in the younger age groups, it was essentially a “contained” gingivitis which appeared to progress towards a periodontitis at a fairly constant but slow rate. The pattern of prevalence and distribution of gingivitis and periodontitis was similar to many modern epidemiological studies on natural dentitions but did not support the view that the prevalence of periodontitis in historic material was high. A small proportion of individuals appeared to be either susceptible or resistant to periodontal disease. It was concluded that the study of historic material provides valuable information with regard to the natural history of human periodontal disease.
Synthesis of type VIII collagen by epithelial cells of human gingiva
Authors: Salonen Jukka , Oda Dolphine , Funk Sarah E. , Sage Helene
Published: July 2006

The composition of the extracellular matrix produced by epithelial cells in contact with metabolically inert substrata was studied with antibodies specific for type VIII collagen. Type VIII collagen was present in the cell layer of cultured gingival epithelial cells, and at the epithelium‐substratum interface of an explant culture model for junctional epithelium. Samples of the epithelial attachment apparatus (EAA) in vivo were collected by removing the junctional cells directly attached to the tooth (DAT cells) and the associated EAA matrix. The amount of material collected was sufficient for biochemical analysis of both intra‐ and extracellular components of the junctional cell‐EAA complex. Immunological examination of the samples revealed that type VIII collagen was associated with epithelial cells forming the EAA in vivo. We suggest that this collagen type functions in the extracellular space as an attachment‐promoting factor for gingival epithelial cells at the tooth surface.
Multicenter evaluation of tetracycline fiber therapy: I. Experimental design, methods, and baseline data
Authors: Goodson J. M. , Cugini M. A. , Kent R. L. , Armitage G. C. , Cobb C. M. , Fine D. , Fritz M. E. , Green E. , Imoberdorf M. J. , Killoy W. J. , Mendieta C. , Niederman R. , Offenbacher S. , Taggart E. J. , Tonetti M.
Published: July 2006

The study design and baseline characteristics of a multicenter trial to test the effectiveness and safety of locally delivered tetracycline for treatment of adult periodontitis are described. Local delivery was provided by 0.5 mm diameter ethylene vinyl acetate copolymer fibers loaded 25% with tetracycline hydrochloride which were placed into periodontal pockets and maintained by an adhesive for 10 (±2) days. A total of 113 subjects (56 male and 57 female; mean age 49.3 yr) at five centers participated in the study. Subjects were selected who had 4 nonadjacent teeth with 6–10 mm pockets that bled on probing. The selected sites in each subject were randomly assigned to 4 test groups: tetracycline fiber, control fiber, scaling with root planing, or untreated. A balanced experimental design was thereby established in which each subject contributed equally by providing 4 clinically comparable sites for evaluation. To provide a more specific model for testing periodontitis therapy, gingivitis was treated prior to the initiation of the study by prophylaxis with supragingival calculus removal and home care instruction. Clinical response variables measured were pocket depth reduction, attachment level gain and bleeding on controlled‐force probing measured at baseline, 30 d, and 60 d. Levels of 6 bacterial species selected as probable periodontal pathogens were measured by DNA probe analysis of plaque samples. The design of this study provided several unique analytical opportunities. Controls included a comparison with conventional treatment, analysis of vehicle effects, and effects at untreated sites. Comparison of the test group with controls permitted evaluation of the principal variables that could effect interpretation of results. The balanced design created by equal representation of each subject in each test provided means to compensate for individual differences between subjects. The combination of these factors resulted in an experimental design which addresses many of the concerns that have been expressed relating to the conduct of clinical trials of periodontal treatments.
Ultrastructural localization of alkaline and acid phosphatase activities in dental plaque
Authors: Lo Storto S. , Silvestrini G. , Bonucci E.
Published: July 2006

Ultrastructural cytohistochemical techniques showed presence of acid and alkaline phosphatases in dental plaque. Both phosphatases had intra‐ and extramicrobial localization. In the extracellular matrix, phosphatases were associated with small vesicles of bacterial origin, or were freely scattered in the matrix without apparent connection with microbial structures. Intracellularly, alkaline (AlkP) and acid (AcP) phosphatases were observed in Gram‐negative and Gram‐positive bacteria, showing a different localization. The AlkP was mainly located in the periplasmic space, while AcP had a double preferential localization: along the outer surface of the cell wall and in the periplasmic space. Less frequently an intracellular phosphatase reaction was seen in the cytoplasm.
Enhanced collagen phagocytosis by rat molar periodontal fibroblasts after topical application of lipopolysaccharide – Ultrastructural observations and morphometric analysis
Authors: Ljuhin Naokuni , Miyauchi Mutsumi , Ito Hiroshi , Takata Takashi , Ogawa Ikuko , Nikai Hiromasa
Published: July 2006

To investigate the effect of lipopolysaccharide (LPS) on phagocytic activity of collagen fibrils by periodontal fibroblasts, we studied rat molar gingival connective tissue and periodontal ligament under light and electron microscopy after topical application of LPS (5 mg/ml in physiological salt solution (PS)) on the gingival sulcus. Phagocytic activity of collagen fibrils by fibroblasts was evaluated by counting the number of collagen‐containing vacuoles inside fibroblasts that were present within a defined area (1200 μm2). Values obtained from fibroblasts in the subepithelial connective tissue, the region near the alveolar crest, and the middle region of periodontal tissue were compared. Periodontal ligament fibroblasts showed increased phagocytosis of the collagen fibrils from 3 hours to 1 day after topical LPS application, but no differences were observed in the gingival tissue. The intracytoplasmic vacuoles containing collagen fibrils were of various sizes and shapes, showing positive for acid phosphatase and/or alkaline phosphatase reaction. Collagen phagocytic activity of the fibroblasts in the middle region of the periodontal ligament also increased after PS treatment. However, this was significantly less than that observed in LPS‐treated animals (p<0.01). This study indicates that LPS may enhance the degradation of collagen by stimulating the phagocytic activity of the periodontal ligament fibroblasts.
Immunoglobulin‐degrading enzymes in localized juvenile periodontitis
Authors: Gregory R. L. , Kim D. E. , Kindle J. C. , Hobbs L. C. , Lloyd D. R.
Published: July 2006

Previous reports have indicated the association of periodontal diseases with elevated levels of serum immunoglobulin G (IgG) antibodies to periodontally relevant bacteria. Recent results from this laboratory suggest that enzymes proteolytic for immunoglobulins are important virulence factors of several periodontal bacteria. Specifically, enzymes from Porphyromonas (Bacteroides) gingivalis culture supernatant fluid (SF) cleaved human IgG (4 subclasses), IgAl and IgA2, IgM, IgD and IgE. Proteolytic enzymes from Actinobacillus actinomycetemcomitans culture SF cleaved IgG, IgA and IgM. An enriched Ig proteolytic preparation from Capnocytophaga ochracea culture SF was shown to extensively cleave all 4 subclasses of human IgG. Extensive degradation of IgG and IgA in crevicular fluid samples on SDS‐PAGE from periodontal disease sites of localized juvenile periodontitis (LJP) patients in comparison to little degradation in healthy sites indicated the potential role the proteolytic enzymes from periodontopathogenic bacteria may play in situ. Treatment of IgG with P. gingivalis, A. actinomycetemcomitans and C. ochracea SF resulted in similar patterns of degradation. LJP patients had significantly higher levels of IgG and IgA proteolytic activity in whole saliva than age, sex, and race‐matched periodontal disease‐free controls. However, not all of the proteolytic activity could be ascribed to Bacteriol proteases since neutrophils are also present in large numbers at diseased sites. Using similar techniques, lysates of neutrophils from healthy controls cleaved IgG, IgA and IgM. The observation of enhanced Ig cleavage activity in crevicular fluid and saliva in LJP patients suggest a role for Ig proteolytic enzymes in LJP.
Periotest for measuring periodontal characteristics–Correlation with periodontal bone loss
Authors: Schulte W. , D'Hoedt B. , Lukas D. , Maunz M. , Steppeler M.
Published: July 2006

The Periotest measures the reaction of the periodontium to a defined percussive force. The percussion is applied to the tooth by an electronically controlled tapping head. Information on structural change is obtained by measurement of both the elastic and viscous characteristics of the periodontium. The latter prevent oscillations of the tooth in the alveolar bone. A value is calculated and is displayed as a “Periotest value”. The following research report shows the relation of Periotest values to bone loss. Bone loss was quantitatively determined for 2312 teeth from orthopantomographic radiographs and for 900 teeth exposed to intra‐oral films using the standard paralleling technique. A differentiation was made between vertical and horizontal bone loss. Clinical mobility index, pocket depth, gingival recession and papillary hemorrhagic index were also measured. There was a strong association between the Periotest value and bone loss. These results suggest that Periotest evaluation provides an objective indication of the extent of periodontal bone loss.
Morphology of neural endings in the human periodontal ligament: An electron microscopic study
Authors: Lambrichts I. , Creemers J. , van Steenberghe D.
Published: July 2006

The ultrastructure of sensory nerve endings in the human periodontal ligament from 43 extracted teeth was studied using serial sections. Three types of nerve endings were found: free nerve endings (FNE), Ruffmi‐like endings and lamellated corpuscles. Free nerve endings stem from unmyelinated or from myelinated nerve fibers. The endings contain neurotubuli, neurofilaments and vesicles. Ruffini‐like receptors were mostly found in the apical part of the periodontal ligament. In these Ruffmi‐like receptors a particularly abundant concentration of mitochondria appears. In some cases desmosome‐like junctions are present between neurite and ensheathing cell. Lamellated corpuscles were also found in the periodontal ligament. The lamellae are extremely endocytotic and are in close contact with each other.
Effects of NSAIDs on beagle crevicular cyclooxygenase metabolites and periodontal bone loss
Authors: Offenbacher S. , Williams R. C. , Jeffcoat M. K. , Howell T. H. , Odle B. M. , Smith M. A. , Hall C. M. , Johnson H. G. , Goldhaber P.
Published: July 2006

This investigation focuses on the changes in the concentrations of cyclooxygenase (CO) products present within the crevicular fluid in naturally‐progressing periodontitis in the beagle and the effects of various non‐steroidal anti‐inflammatory drugs (NSAIDs) on these metabolite levels and disease progression. Six groups of 5–6 beagles with periodontitis were followed for 6 months to determine the pretreatment rate of radiographic bone loss. At baseline, groups of animals were placed on soft chow to promote disease progression. Groups were treated with either placebo, three different formulations of systemic ibuprofen, systemic naproxen or topical flurbiprofen. During the 6‐month treatment phase, crevicular fluid (CF) samples and radiographs were taken at regular intervals. Radioimmunoassay of CF samples from untreated animals demonstrated a steady increase in prostaglandin E2 (PGE 2) over baseline values. At 1 month, CF‐PGE2 levels increased 2‐fold over baseline and, by 6 months, had reached a 5‐ to 6‐fold elevation. Crevicular fluid thromboxane B2 (CF‐TxB2) levels rapidly reached a 4‐ to 5‐fold peak over baseline at 1 month and subsequently dropped to a 2‐fold elevation for the remainder of the study. The rate of bone loss (BLOSS) in untreated animals increased 38% during the 6‐month period, as compared to baseline pretreatment BLOSS rates. Overall, there was a significant depression in the CF levels of both PGE2 and TxB2 in all NSAID‐treated groups. All NSAID treatments significantly retarded BLOSS, ranging from 21.0–36.9% of the control BLOSS rate. The topical application of flurbiprofen was as effective in depressing CF levels of PGE2 and TxB2 as systemic or sustained release formulations of other NSAIDs. The data further substantiate the concept that much of the BLOSS that occurs in periodontal disease is mediated by products of the cyclooxygenase pathway. Furthermore, CO activation represents a major regulatory step in bone destruction and may thereby serve as an important site for pharmacological modulation.
The periodontal differentiation in the phylogeny of teeth–an overview
Authors: Gaengler P. , Metzier E.
Published: July 2006

During the evolution of teeth, different types of periodontal attachment have been developed. On the basis of the comparative histology of periodontal tissues, protoacrodontal, acrodontal, acro‐protothecodontal, pleurodontal and thecodontal structures can be distinguished that depend upon the area of attachment (crestal, marginal or socketed type) and the mode of attachment (ankylosis, fibrous or combined type). Due to “phylogenetic memory”, changes of the peri‐odontium in health and disease could be interpreted as copies of phylogenetically older patterns. The greatest variations in tooth attachment have originated in acrodont bony fishes and in pleurodont reptiles, whereas the selection for a single thecodont or socketed type was an important event in the evolution of mammals. The detailed structures of cementum, of the fiber apparatus and of the junctional epithelium vary from type to type and within one type. These principal structures are decisive for reaction patterns of degeneration and regeneration. Therefore, comparative periodontology could be an important adjunct to help interpret the natural history of periodontal diseases, to help in the selection of experimental animals and to help provide treatment strategies in both human and veterinary situations.
Influence of oral hygiene on elastase concentration of gingival crevicular fluid
Authors: Meyle J. , Zell St. , Brecx M. , Heller W.
Published: July 2006

PMN elastase concentration of gingival crevicular fluid (GCF) was investigated in 11 healthy volunteers before professional tooth cleaning and after a 5‐week period of intensive oral hygiene. GCF was collected using filter paper strips and the enzyme concentration was evaluated by the ELISA‐technique. Intensive daily oral hygiene led to a considerable improvement in the clinical indices and to a reduction in the concentration of elastase in GCF. Despite the changes in the oral hygiene status, functional elastase was still present in the samples at the end of the experiment. This could mean that even at clinically healthy sites there is a lack of alpha‐1‐proteinase inhibitor, the major serum protein inactivating PMN elastase.
Volatile sulfur compounds in mouth air from clinically healthy subjects and patients with periodontal disease
Authors: Yaegaki K. , Sanada K.
Published: July 2006

Volatile sulfur compounds (VSC) in mouth air were estimated by gas chromatography. The amount of VSC and the methyl mercaptan/ hydrogen sulfide ratio were significantly increased in patients with periodontal disease. These two parameters also increased in proportion to the bleeding index and probing depth. A study was also done on the effect of removal of tongue coating on VSC concentrations in mouth air from patients with periodontal involvement. VSC and the methyl mercaptan/hydrogen sulfide ratio were reduced to 49% and 35%, respectively, by removal of the tongue coating. The average amount of tongue coating removed from patients with periodontal disease was significantly higher than from controls (90.1 mg vs. 14.6 mg, p < 0.01). Estimated production of VSC from tongue coating was 4 times higher than the control value, and the methyl mercaptan/hydrogen sulfide ratio was also markedly increased. However, a saliva putrefaction study suggested that saliva does not contribute to the elevated ratio of methyl mercaptan in mouth air. These results strongly suggest that, in addition to periodontal pockets, tongue coating has an important role in VSC production, in particular leading to an elevated concentration of methyl mercaptan, which is more pathogenic than hydrogen sulfide.
Effect of interleukin‐1β on gene expressions and functions of fibroblastic cells derived from human periodontal ligament
Authors: Takeshita Akira , Niu Zhon Gying , Hanazawa Shigemasa , Takara Iwao , Higuchi Hiroaki , Katayama Ikuemon , Kitano Shigeo
Published: July 2006

The present study shows the effect of interleukin‐1β (IL‐1β) on some gene expressions and functions of fibroblastic cells (HPLF) derived from human periodontal ligament. HPLF were used at passages number 5 to 10. IL‐1β increased DNA synthesis in both a dose‐ and an incubation time‐dependent manner. IL‐1β in combination with tumor‐necrosis factor α or transforming growth factor β synergistically stimulated the DNA synthesis in the cells. Since many studies have shown that the c‐myc oncogene is involved in cell proliferation and differentiation, the effect of IL‐1β on c‐myc messenger RNA (mRNA) level in HPLF was examined. IL‐1β induced a marked c‐myc mRNA level in the cells at 90 minutes after initiation of the cytokine treatment. On the other hand, IL‐1β significantly inhibited alkaline phosphatase (ALP) activity of the cells in a dose‐dependent manner. Also an inhibitory effect was observed on the liver/bone/kidney ALP mRNA level of the cells, and this inhibition by IL‐1β was dose‐ and incubation time‐dependent. These results suggest that IL‐1β is a regulatory cytokine involved in the regeneration of the human periodontal ligament.
Neutrophil modulation by Actinobacillus actinomycetemcomitans I. Chemotaxis, surface receptor expression and F‐actin polymerization
Authors: Ashkenazi Malka , White Robert R. , Dennison David K.
Published: July 2006

Localized juvenile periodontitis is an early onset periodontitis, usually localized to molars and incisors. Patients usually present with decreased chemotaxis of systemic neutrophils (PMNs) and infection with Actinobacillus actinomycetemcomitans. The pathogenic mechanisms involved have not been clarified. The purpose of this study was to determine if an extract of A. actinomycetemcomitans could induce changes in PMN chemotaxis similar to those reported in LJP patients. It was demonstrated that the bacterial extract was chemotactic for neutrophils. When neutrophils were pre‐incubated with the bacterial extract, chemotaxis toward zymosan‐activated serum, FMLP and the bacterial extract was inhibited in two different chemotaxis assays (Boyden chamber and under‐agarose). Bacterial extract had no effect on random migration in either assay. Pre‐incubation with the extract induced increased expression of CD11b/CD18 (Mac‐l), Gp110, and FMLP receptors and increased F‐actin polymerization following FMLP or PMA stimulation compared to cells not treated with the extract. Treatment of the bacterial extract with proteinase K or phenol extraction reversed the PMN chemotaxis inhibition activity, but increased significantly the random migration of PMNs. Heating the bacterial extract to 56°C had no effect on its activity. The component(s) in the bacterial extract that inhibits chemotaxis is therefore a protein(s), not sensitive to 56 C, and is not endotoxin. This study suggests that A. actinomycetemcomitans may contribute to the pathogenesis of localized juvenile periodontitis by inhibiting chemotaxis. Interference with chemotaxis by A. actinomycetemcomitans, however, occurs through a mechanism other than inhibition of actin assembly, reduction of CD1 lb/CD18 or Gp110 expression, or blockage/downregulation of FMLP receptors.
Platelet‐derived and insulin‐like growth factors stimulate regeneration of periodontal attachment in monkeys
Authors: Rutherford R. B. , Niekrash C. E. , Kennedy J. E. , Charette M. F.
Published: July 2006

Regeneration of cementum, ligament, bone and new attachment was achieved by introducing mixtures of recombinant human platelet‐derived growth factor and insulin‐like growth factor into debrided lesions of experimentally induced periodontitis in monkeys. This growth factor therapeutic regimen induced the regeneration of nearly 50% of the lost attachment within 4 weeks. New attachment in some cases included regeneration of horizontally resorbed interdental septa. These observations suggest that predictable, clinically significant gains in new attachment may be possible through the use of highly purified human recombinant growth factors delivered to debrided lesions of adult periodontitis in appropriate, inert carrier vehicles.
Distribution of ICAM‐1, LFA‐3 and HLA‐DR in healthy and diseased gingival tissues
Authors: Crawford John M.
Published: July 2006

Cell adhesion molecules are involved in recognition and effector aspects of the host response, including the control of migration of leukocytes into inflammatory sites. In this study we have demonstrated that the distribution of three cell‐surface molecules involved in cell interactions, ICAM‐1, LFA‐3 and HLA‐DR is distinct and different in healthy and diseased gingival tissue. ICAM‐1 was consistently expressed by junctional epithelial cells in healthy gingiva and by pocket epithelium in diseased gingiva but was not detectable on the majority of keratinocytes in external gingival epithelium. ICAM‐1 was also expressed by endothelial cells of gingival blood vessels and a subset of leukocytes in the infiltrated connective tissue in both healthy and diseased gingiva. HLA‐DR and LFA‐3 were also expressed by epithelial cells and endothelial cells but in patterns which were distinctly different from ICAM‐1.
General design issues in efficacy, equivalency and superiority trials
Authors: Fleiss Joseph L.
Published: July 2006

Critical discussion is offered of design issues pertinent to three categories of clinical trials: efficacy trials, in which an experimental intervention is compared to an inert control, and equivalency and superiority trials, in which an experimental intervention is compared to an active control. The issues discussed are sample‐size determination and power, problems in designing and analyzing multicenter trials, broad versus concentrated sampling of patients, the need (or not) for a placebo control group in an active control trial, the possible appropriateness of crossing patients over from one regimen to another, various methods of randomization, the intention‐to‐treat principle in repeated measurements studies, and possible logical conflicts between inferences from superiority trials and inferences from equivalency trials.
Biological and measurement issues critical to design of gingivitis trials
Authors: Caton Jack
Published: July 2006

Chronic plaque‐induced gingivitis is usually of little consequence, thus the concern about prevention and treatment must stem from the belief that pre‐existing gingivitis is necessary for periodontitis to develop. When clinical signs of gingivitis are present, an inflammatory infiltrate can be found upon histological evaluation. When clinical signs are absent, however, significant inflammation may still be present within the gingival tissues. Therefore, multiple clinical evaluations should be made, with special attention given to the visually inaccessible midinterdental area. The “gold standard” for evaluation of gingivitis is histological evaluation and other measurements should be evaluated against this standard. The significance of clinical severity measurements of gingivitis is not well‐understood relative to onset of periodontitis; therefore, it is suggested that consideration be given to gingival evaluations based on the presence or absence of clinical signs of inflammation. Furthermore, equivalency and superb ority of antigingivitis agents or devices should be predicated, at least in part, on their ability to prevent the onset of periodontitis.
Design issues specific to studies of periodontitis
Authors: Page R. C. , DeRouen T. A.
Published: July 2006

Guidelines for clinical trials demonstrating equivalence or superiority for treatments for periodontitis are badly needed because of the great variety of drugs, agents, and devices now being developed. This paper focuses on three design issues. These are primary outcome variables and their measurement, disease‐active vs disease‐inactive sites and patients, and study duration. Determinants for selection of outcome variables include the biologic events to be observed, changes that are specific for periodontitis, and methods chosen to detect those changes. The primary outcome variables specific for periodontitis and appropriate for use in clinical trials are periodontal attachment level and alveolar bone status. Improved methods for measurement of both with excellent accuracy and reproducibility are now becoming available. Studies performed on untreated patients over the past decade demonstrate clearly that disease‐active and disease‐inactive pockets exist, at any given point in time most are inactive, disease progression is episodic and in most patients infrequent, and a rather small portion of the population—possibly around 5%—are unusually susceptible to rapid disease progression. These observations need to be taken into account in enrolling subjects into periodontitis clinical trials. Conducting a prestudy to identify actively diseased sites and susceptible subjects, or screening to enrich the proportion of active sites, is recommended. Determination of study duration is a very complex issue. It is related to the length of time required for maximal change and stabilization to occur in the biological events to be observed, the outcome variable(s) used to detect change, and the nature of the therapeutic interventions to be studied. No single duration is applicable to all periodontitis clinical trials. Large gaps in our knowledge about the design of periodontitis trials still exist, and additional research is needed.
Correlation between tumor necrosis factor‐α (TNF‐α)‐induced cytoskeletal changes and human collagenase gene induction
Authors: Gronowicz G. , Hadjimichael J. , Richards D. , Cerami A. , Rossomando E. F.
Published: July 2006

Tumor necrosis factor‐alpha (TNF‐α) has been shown not only to induce the biosynthesis and secretion of collagenase but also to change the organization of cytoskeletal components. In the present study we explore the correlation between the biosynthesis of collagenase (by mRNA hybridization, indirect immuno‐fluorescence and collagenolytic activity), and cytoskeletal reorganization (by rhodamine‐phalloidin staining of F‐actin) induced in fibroblasts by recombin‐ant TNF (rTNF). In the concentration range of 1–100 ng/ml, rTNF increased extracellular collagenase activity 8‐fold and collagenase mRNA 4‐fold. In addition, whereas the collagenase mRNA was detected as early as 24 h post‐treatment, the appearance of extracellular collagenase activity required 48 h. Using phalloidin to follow the organization of the cytoskeleton we observed that rTNF disrupted the parallel array of stress fibers normally observed in the perinuclear region. In contrast to the time required to affect collagenase synthesis, the effect of rTNF on stress fiber organization occurred as early as 6 h post‐treatment. Finally, while the number of cells exhibiting this change increased with increasing concentrations of rTNF, a maximum of about 30% of the cells showed this effect. Interestingly, double staining studies demonstrated that both stress fiber changes and procollagenase production occurred in the same cells. This finding, together with the observation that the cytoskeletal disorganization preceded collagenase gene induction by at least 18 h is consistent with the conclusion that the organizational status of the microfilaments may have a role as a regulator of procollagenase gene expression.
Relationship between bacterial counts, microbial vitality and the accumulation of supragingival dental plaque in humans
Authors: Weiger R. , Netuschil L. , Brecx M.
Published: July 2006

Comparisons between plaque index (PII) and bacterial counts have been made already; however, these did not take into account the area used for plaque sampling. The objective of the present study was to determine the correlation between the PII score, the number of bacteria and the bacterial plaque vitality when dental plaque was repeatedly sampled from the same area in each subject during early plaque accumulation. Between intervals of optimal oral hygiene, 10 participants refrained from all oral hygiene measures for periods of 1, 2, 3, 4 and 5 days. The PII was recorded on the vestibular surface of all first premolars as local PII:LS. For statistical reasons, the scores of the independent variable LS were added for each subject giving LS* values ranging from 0 to 8. The plaque sampled from this specific surface was circumscribed by the marginal gingiva and an acrylic splint, giving reproducible areas for plaque collection. Total microscopic bacterial counts (BC), colony forming units of anaerobes (CFUan) and aerobes (CFUae), and proportions of vital bacteria (VF) were compared with LS* values. BC and LS* values were strongly correlated. CFUan and CFUae increased significantly with LS*, but this increase was higher for LS* 0 to 4 than for LS* 4 to 8. The ratio between vital and dead microorganisms, assessed by two different methods, was low when an LS* of 0 was recorded, with higher ratios registered for LS* values 4 and 8.
Vascular reaction in plaque‐induced gingivitis: A quantitative approach
Authors: Bergström Jan
Published: July 2006

The clinical diagnostic features of gingivitis such as redness, swelling and bleeding are based on vascular changes. It would be desirable to directly make use of the vascular changes in the clinical evaluation of gingival inflammation. In the present study, capillary microscopy was used for quantitative evaluation of the vascular reaction of the marginal gingiva in response to experimental plaque formation in 6 healthy students. Low power stereomicroscopy was used and the number of vessel endings was evaluated from stereophotographs. A gradual increase in the number of visible vessel endings was observed over time of plaque accumulation. The mean ± SEM at baseline was 24.0 ± 6.30 as compared to 77.0 ± 10.02 at day 28. After removal of plaque and re‐institution of oral hygiene measures, a return toward pre‐experimental numbers was observed. Throughout the test the number of vessel endings within the proximal‐papillary part of the marginal gingiva was less than that within the basal‐labial part. The results indicate that low power stereophotomicroscopy is a useful tool for the clinical study of inflammatory changes in the gingival vasculature.