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    Michael Sela

    This study was carried out to examine the release kinetics of chlorhexidine from a sustained release device (S. R. D.) prepared from ethyl cellulose (fast S. R. D.) or ethyl cellulose with polyethylene glycol (slow S. R. D.) and to... more
    This study was carried out to examine the release kinetics of chlorhexidine from a sustained release device (S. R. D.) prepared from ethyl cellulose (fast S. R. D.) or ethyl cellulose with polyethylene glycol (slow S. R. D.) and to examine the effects on the bacterial flora of pockets in patients with periodontal disease.It was shown that fast S. R. D.'s release up to 80% of the chlorhexidine within the first 3 days in insertion in periodontal pockets, whereas the slow S. R. D.'s release 50% of the chlorhexidine content after 6 days. The release kinetics of chlorhexidine from S. R. D.'s placed in pockets as expressed by the Higuchi system (Higuchi 1963) indicate that it is diffusion controlled. The rate of chlorhexidine release is dependent on the structure of S. R. D., the drag concentration within the device, and the effective surface area.The microbial flora of sixteen pockets from 6 patients were examined using darkfield microscopy at day 0, 3, 10, and 14 after treatment with S. R. D.'s containing, chlorhexidine or placebo S. R. D.'s. The pocket depths ranged from 5–8 mm. The chlorhexidine‐treated group showed a marked decrease in the relative proportions of motile rods and spirochetes and a corresponding increase in non‐motile organisms compared to the flora prior to chlorhexidine treatment or compared to the flora of the placebo treated pockets. These differences were significant up to 10 days post treatment (P < 0.0025).The study indicated the effectiveness of ethyl cellulose polymers as S. R. D.'s in vivo and their ability to reduce the relative proportions of the motile organisms of periodontal pockets to negligible amounts.
    A Porphyromonas endodontalis ATCC 35406 protease was purified from Triton X-114 cell extracts by preparative SDS-PAGE followed by electroelution. The purified enzyme exhibits a molecular size of 88 kDa and was dissociated into two... more
    A Porphyromonas endodontalis ATCC 35406 protease was purified from Triton X-114 cell extracts by preparative SDS-PAGE followed by electroelution. The purified enzyme exhibits a molecular size of 88 kDa and was dissociated into two polypeptides of 43 and 41 kDa upon heating in the presence of sodium dodecyl sulfate with or without a reducing agent. The protease (pH optimum 7.5-8.0) degraded the extracellular matrix proteins fibrinogen and fibronectin. Collagen IV was also degraded at 37 degrees C but not at 28 degrees C. The protease also cleaved the bioactive peptide angiotensin at amino acid residue phenylalanine-8 and tyrosine-4 but failed to hydrolyze bradykinin, vasopressin and synthetic chromogenic substrates with phenylalanine or tyrosine at the P1 position. In addition, two peptidases were detected in P. endodontalis cells: a proline aminopeptidase that remained associated with the cell pellet after detergent extraction and peptidase/s that partitioned into the Triton X-114 phase after phase separation and degraded the bioactive peptides bradykinin and vasopressin. These P. endodontalis peptidases and proteases may play an important role in both the nutrition and pathogenicity of these assacharolytic microorganisms. The inactivation of bioactive peptides and degradation of extracellular matrix proteins by bacterial enzymes may contribute to the damage of host tissues accompanied with endodontic infections.
    The present study compares periodontal parameters, caries, and levels of colony forming units (CFU) of bacteria from subgingival plaque of permanent teeth, to those of primary teeth examined 4 years previously. Six children who had... more
    The present study compares periodontal parameters, caries, and levels of colony forming units (CFU) of bacteria from subgingival plaque of permanent teeth, to those of primary teeth examined 4 years previously. Six children who had periodontitis and 5 who had no periodontitis in primary teeth (groups A and B respectively) were examined. The microbial examination included the number of CFU of the total anaerobic count, Actinobacillus actinomycetemcomitans, Streptococcus mutans and Porphyromonas gingivalis. The differences in CFU values for the permanent teeth between groups A and B were not significant. Group A had significantly higher gingival inflammation values in the permanent teeth than group B. Permanent teeth had significantly higher CFU values of P. gingivalis than the primary teeth. Based on the present limited sample, the number of CFU from bacteria of the subgingival plaque of primary teeth are not an adequate predictor of periodontal disease or caries in the permanent teeth.
    In vivo adsorption of salivary albumin and α-amylase onto titanium, enamel and dentin was analysed following their exposure to the oral cavity for 2 h. Oral appliances in six adults served as a platform for carrying 4-mm discs of the... more
    In vivo adsorption of salivary albumin and α-amylase onto titanium, enamel and dentin was analysed following their exposure to the oral cavity for 2 h. Oral appliances in six adults served as a platform for carrying 4-mm discs of the three materials. Adherent proteins were eluted from the discs and the amounts of salivary albumin and α-amylase were measured by an enzyme-linked immunosorbent assay. While no significant difference between the adsorption of albumin and α-amylase onto enamel as compared with dentin was observed, adsorption onto titanium was significantly lower. A sample of whole saliva was also collected from each participant. The mean total amounts of albumin and α-amylase in the participants' whole saliva were 0.03 and 0.54 mg ml−1, respectively. Titanium adsorbed significantly less (4.43%) of the total albumin than did enamel (14.30%) or dentin (18.80%). No significant difference was found in the relative amounts of α-amylase adsorbed by the three materials. This significantly selective adsorption of proteins may enable the attachment of specific bacteria and thus alter the composition of the dental plaque and its potential pathogenicity.
    The predominant subgingival microflora, host immune response, and genetic history of a 14-year-old girl with Papillon-Lefèvre Syndrome (PLS) are reported. The patient had high counts of Actinobacillus actinomycetemcomitans and surface... more
    The predominant subgingival microflora, host immune response, and genetic history of a 14-year-old girl with Papillon-Lefèvre Syndrome (PLS) are reported. The patient had high counts of Actinobacillus actinomycetemcomitans and surface translocating bacteria. She had significantly raised levels of antibodies to five of the bacterial species studied with the levels to A. actinomycetemcomitans remaining high after antibiotic therapy. The polymorphonuclear leukocytes (PMN) also released significantly increased amounts of O2 compared to controls. The data presented support a role for A. actinomycetemcomitans and PMN dysfunction in the pathogenesis of PLS.
    The present study describes the prevalence of alveolar bone loss (ABL) in children in relation to caries, contact and space loss. In addition, the microbial composition of the subgingival plaque of 20 sites, from 5 children, is presented.... more
    The present study describes the prevalence of alveolar bone loss (ABL) in children in relation to caries, contact and space loss. In addition, the microbial composition of the subgingival plaque of 20 sites, from 5 children, is presented. Bite-wing radiographs from 500 children were examined. ABL was evident in: 99 sites from 60 children; > 1 site in 27 children; the maxilla only in 34 children; the mandible only in 17 children; both arches in 9 children; 37 sites with no caries; 4.9 percent of all sites with proximal caries; 15.8 percent of all sites with contact loss; and 20.5 percent of all sites with mesial drift. Anaerobic bacteria were cultured from all 20 sites. No significant differences in the percentages of colony forming units of Actinobacillus actinomycetemcomitans and black pigmented Bacteroides were found among sites with/without bone loss, with/without caries or probing depths smaller/equal or larger than 2.5 mm.
    Among periodontal anaerobic pathogens, the oral spirochetes, and especially Treponema denticola, have been associated with periodontal diseases such as early-onset periodontitis, necrotizing ulcerative gingivitis, and acute pericoronitis.... more
    Among periodontal anaerobic pathogens, the oral spirochetes, and especially Treponema denticola, have been associated with periodontal diseases such as early-onset periodontitis, necrotizing ulcerative gingivitis, and acute pericoronitis. Basic research as well as clinical evidence suggest that the prevalence of T. denticola, together with other proteolytic Gram-negative bacteria in high numbers in periodontal pockets, may play an important role in the progression of periodontal disease. The accumulation of these bacteria and their products in the pocket may render the surface lining periodontal cells highly susceptible to lysis and damage. T. denticola has been shown to adhere to fibroblasts and epithelial cells, as well as to extracellular matrix components present in periodontal tissues, and to produce several deleterious factors that may contribute to the virulence of the bacteria. These bacterial components include outer-sheath-associated peptidases, chymotrypsin-like and tryps...
    An endotoxin was isolated from Capnocytophaga sputigena strain 4 by a modification of the hot phenol-water method. The extraction procedure yielded a lipopolysaccharide which accounted for approximately 1.5% of the dry weight of the... more
    An endotoxin was isolated from Capnocytophaga sputigena strain 4 by a modification of the hot phenol-water method. The extraction procedure yielded a lipopolysaccharide which accounted for approximately 1.5% of the dry weight of the cells. The material was composed of 18.6% lipid (as C 15 fatty acid), 46.5% neutral sugar including 9.6% hexose, 18.3% 6-deoxy sugar, 1.0% 2-keto-3-deoxy sugar, and 4.8% heptose. Hexosamine, protein, and phosphorus were found in quantities amounting to 9.0, 2.9, and 2.0% of the dry weight, respectively. No pentose or nucleic acid was detected. Acid hydrolysis resulted in the release of the constituent sugars and the formation of an insoluble precipitate. The lipopolysaccharide was tested for numerous biological activities characteristic of endotoxins. The pyrogenicity was relatively low; the fever index 40 was 17 μg, and 10 μg was required to give the characteristic biphasic fever response. The toxicity of the extract was very low, with a 50% chicken emb...
    Degradable protein matrices containing chlorhexidine were tested as intra-pocket drug delivery systems in the treatment of periodontal diseases. The properties of the device were mainly dependent upon the degree of cross linking in the... more
    Degradable protein matrices containing chlorhexidine were tested as intra-pocket drug delivery systems in the treatment of periodontal diseases. The properties of the device were mainly dependent upon the degree of cross linking in the matrix, which could be varied according to the preparative conditions. The degree of cross linking was determined by amino acid analysis based on the amount of free lysine in the protein. The release of chlorhexidine and of the plasticizer used in the preparation of the matrix were determined. The release of chlorhexidine from the matrix was prolonged for a period of 300 hours, and the release of plasticizer ceased after four hours. Limited clinical trials suggest that one of the degradable devices--that containing the highest amount of cross-linking--causes a significant reduction in the amount of perio-pathogenic bacteria following its insertion into the periodontal pockets of patients with periodontal disease.
    The suppression of S. mutans is a predominate factor in preventing tooth decay. Sustained-release-delivery varnish of chlorhexidine was applied to dental plastic shells and administered to eight volunteers to be worn while sleeping.... more
    The suppression of S. mutans is a predominate factor in preventing tooth decay. Sustained-release-delivery varnish of chlorhexidine was applied to dental plastic shells and administered to eight volunteers to be worn while sleeping. Salivary bacterial samples were taken on days 0, 7, 14, 21, 28, 35. A statistically significant reduction in S. mutans counts was recorded during the course of the study while a non-significant reduction in the total bacterial counts was found. Our results indicate that the application of chlorhexidine in the form of slow-release varnish in plastic shells is an effective intraoral drug delivery system resulting in reduction of S. mutans.
    Localized aggressive periodontitis (LAgP) is an infectious periodontal disease which generally affects young people. Recent data suggest the involvement of different bacterial species in different populations. The causative bacterial... more
    Localized aggressive periodontitis (LAgP) is an infectious periodontal disease which generally affects young people. Recent data suggest the involvement of different bacterial species in different populations. The causative bacterial species in Israel has never been identified despite a high prevalence of LAgP in this population. The objectives of this study were to characterize the bacterial microbiota of periodontal pockets within an Israeli LAgP population who were also clinically assessed. Twenty-one LAgP patients (test) and 12 chronic periodontitis patients (control) were examined. Bacterial samples were collected from periodontal pockets and analysed by both culture and polymerase chain reaction techniques. Mann-Whitney U test and chi-square test were used to compare results between the groups. Higher levels of Parvimonas micra (>10(6) ), Aggregatibacter actinomycetemcomitans (>10(5) ), Fusobacterium nucleatum/F. periodonticum (>10(6) ), and Tannerella forsythia (leve...
    The presence of microorganisms in the inflamed pulp tissue was already demonstrated in 1894 by Miller (1), who suggested a possible linkage between oral bacteria and the etiology of pulp disease. A convincing evidence implicating bacteria... more
    The presence of microorganisms in the inflamed pulp tissue was already demonstrated in 1894 by Miller (1), who suggested a possible linkage between oral bacteria and the etiology of pulp disease. A convincing evidence implicating bacteria as an were investigated (3-7). A correlation between specific oral bacteria and the clinical manifestations of periapical disease was recently demonstrated by Sundquist (8). The prognosis of root canal therapy after achieving
    The in vitro effect of lithium (Li) on growth and adherence of Streptococcus mutans 6715 in the presence and absence of sucrose was examined by means of optical density and transmission electron microscopy. In the non-sucrose assay,... more
    The in vitro effect of lithium (Li) on growth and adherence of Streptococcus mutans 6715 in the presence and absence of sucrose was examined by means of optical density and transmission electron microscopy. In the non-sucrose assay, bacterial growth was depressed and adherence was elevated between concentrations of 1.44-11.52 mmol/L Li. At 7.20 mmol/L Li extracellular material was present on the bacterial wall. Using 11.52-28.08 mmol/L Li resulted in a perfect negative correlation between the increasing concentrations of Li and bacterial growth and adherence (rs = -0.9 and rs = -1, respectively) in both assays. This paper addresses the dichotomy between the low and high Li concentrations regarding the two bacterial parameters studied, as well as their possibly related cariogenic and cariostatic clinical relevance.
    A clinical trial to test the compound glycyrrhizin, the sweet component of licorice, was conducted on 21 dental students. A split-mouth technique of glycyrrhizin application was used. Subjects were instructed to discontinue all oral... more
    A clinical trial to test the compound glycyrrhizin, the sweet component of licorice, was conducted on 21 dental students. A split-mouth technique of glycyrrhizin application was used. Subjects were instructed to discontinue all oral hygiene procedures, but no dietary modifications were imposed. After 3 days a highly significant reduction in plaque was detected in the upper central incisors on the experimental sides compared with the control sides of students' mouths. Comparing all teeth, less plaque was found on experimental sides than on control sides of the mouths. This difference demonstrated a tendency towards statistical significance. After 4 days the quantitative differences between the two halves of the mouths (less plaque on experimental sides) were greater than after 3 days. This pilot study might indicate the potential of glycyrrhizin in controlling dental plaque.
    The effect of local applications of sustained-release delivery polymer containing chlorhexidine as an adjunct to mechanical plaque removal was studied in institutionalized children with Down's syndrome. Thirty children, ages 8-13,... more
    The effect of local applications of sustained-release delivery polymer containing chlorhexidine as an adjunct to mechanical plaque removal was studied in institutionalized children with Down's syndrome. Thirty children, ages 8-13, participated in the study. Clinical parameters (P1I, GI, papillary bleeding) were recorded and bacterial samples from selected permanent teeth were collected and processed before and following treatment. Following the registration of clinical findings and collection of plaque, all children had their teeth scaled and polished and were randomized into three treatment groups of ten subjects each: Subjects in group I had their teeth coated with ethyl cellulose containing chlorhexidine; those in group II had their teeth coated with placebo polymer and those in group III received no further treatment. Individual oral hygiene habits were not interfered with. The application of the solutions to the respective groups was done every 3 days for 21 days. Chlorhexi...
    The clinical and laboratory findings in two siblings affected with Morquio's syndrome are described. The oral findings, consisting of disturbances in the structure of the enamel in both deciduous and permanent teeth,... more
    The clinical and laboratory findings in two siblings affected with Morquio's syndrome are described. The oral findings, consisting of disturbances in the structure of the enamel in both deciduous and permanent teeth, resemble those of amelogenesis imperfecta, Type 1. Preformed crowns are recommended as the initial treatment, in order to avoid loss of vertical height. The dentist's familiarity with the oral manifestations of Morquio's disease may contribute to the early detection of this condition.
    HLA proteins are genetically determined, and account in part for individual immune response. Several studies have been performed seeking an association between HLA antigens and various forms of periodontitis with no conclusive results.... more
    HLA proteins are genetically determined, and account in part for individual immune response. Several studies have been performed seeking an association between HLA antigens and various forms of periodontitis with no conclusive results. The aim of the present study was to determine the frequency of HLA antigens of patients suffering from the localized (LJP) and the generalized (SGP) forms of early-onset periodontitis (EOP). Twenty-six EOP patients from the same ethnic group were studied in comparison to 113 race-matched controls. The EOP group included 11 LJP and 15 SGP patients. HLA-A9 and B15 antigens were found to be significantly elevated in the patient group. These differences were found to be due to the high frequency of A9 and B15 antigens in the SGP patients, with the LJP patient group showing no significant difference from the control group. The results are in agreement with previous studies in which A9 and B15 were found to be associated with EOP. However, previous studies did not differentiate between the localized and the generalized form of EOP. These results support the hypothesis that the generalized and the localized forms of EOP are under different genetic control.
    The secretion of prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) by adherent mononuclear cells (AMNC) from 28 patients with early-onset periodontitis was studied.... more
    The secretion of prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) by adherent mononuclear cells (AMNC) from 28 patients with early-onset periodontitis was studied. The early onset-periodontitis patients consisted of 12 patients with localized juvenile periodontitis (LJP) and 16 patients with severe generalized periodontitis (SGP). The AMNC responses to different concentrations of lipopolysaccharide (LPS) (E. coli) were determined in these 28 patients and compared to 14 healthy controls. Mediator levels in the supernatant were measured using radioimmunoassays for PGE2, IL-1 beta, and IL-6 determination and an enzyme linked immunosorbent assay for TNF alpha levels. The mean age of the patients was 19.9 years for the LJP group, 30.4 years for SGP, and 28.0 years for the controls. The mean number of teeth per patient with attachment loss of > 6 mm was 4.75 in the LJP patients and 17.3 in the SGP group. In the absence of LPS, LJP AMNC secreted significantly more PGE2 than unstimulated control or SGP AMNC, while similar baseline amounts of IL-1 beta, IL-6, and TNF alpha were secreted by AMNC from the 3 patient groups. LPS stimulation resulted in the dose-dependent secretion of significantly higher levels of PGE2 by LJP AMNC compared to SGP AMNC which in turn secreted significantly more than controls. TNF alpha secretion by LJP monocytes was significantly greater than the SGP and the control groups while IL-1 beta secretion by the SGP AMNC was depressed compared to the other two patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)
    ... Fig. 8. Higher magnification of a peripheral area of bridge from Fig. 7. Arrows point to-ward the large defects. X 475. ... Journal of Dentistry for Children 28, 150-153-Nyborg, H. (1955) Healing processes in the pulp on capping. Acta... more
    ... Fig. 8. Higher magnification of a peripheral area of bridge from Fig. 7. Arrows point to-ward the large defects. X 475. ... Journal of Dentistry for Children 28, 150-153-Nyborg, H. (1955) Healing processes in the pulp on capping. Acta Odontologiea Scan-dinavica 13, suppl. 16, 106. ...
    Among periodontal anaerobic pathogens, the oral spirochetes, and especially Treponema denticola, have been associated with periodontal diseases such as early-onset periodontitis, necrotizing ulcerative gingivitis, and acute pericoronitis.... more
    Among periodontal anaerobic pathogens, the oral spirochetes, and especially Treponema denticola, have been associated with periodontal diseases such as early-onset periodontitis, necrotizing ulcerative gingivitis, and acute pericoronitis. Basic research as well as clinical evidence suggest that the prevalence of T. denticola, together with other proteolytic Gram-negative bacteria in high numbers in periodontal pockets, may play an important role in the progression of periodontal disease. The accumulation of these bacteria and their products in the pocket may render the surface lining periodontal cells highly susceptible to lysis and damage. T. denticola has been shown to adhere to fibroblasts and epithelial cells, as well as to extracellular matrix components present in periodontal tissues, and to produce several deleterious factors that may contribute to the virulence of the bacteria. These bacterial components include outer-sheath-associated peptidases, chymotrypsin-like and tryps...
    Host defense peptides are innate immune effectors that possess both bactericidal activities and immunomodulatory functions. Deficiency in the human host defense peptide LL-37 has previously been correlated with severe periodontal... more
    Host defense peptides are innate immune effectors that possess both bactericidal activities and immunomodulatory functions. Deficiency in the human host defense peptide LL-37 has previously been correlated with severe periodontal disease.Treponema denticolais an oral anaerobic spirochete closely associated with the pathogenesis of periodontal disease. TheT. denticolamajor surface protein (MSP), involved in adhesion and cytotoxicity, and the dentilisin serine protease are key virulence factors of this organism. In this study, we examined the interactions between LL-37 andT. denticola. The threeT. denticolastrains tested were susceptible to LL-37. Dentilisin was found to inactivate LL-37 by cleaving it at the Lys, Phe, Gln, and Val residues. However, dentilisin deletion did not increase the susceptibility ofT. denticolato LL-37. Furthermore, dentilisin activity was found to be inhibited by human saliva. In contrast, a deficiency of theT. denticolaMSP increased resistance to LL-37. The...

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