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Biomedical subjects

L Shapira

Publications and source records attributed to L Shapira.

At least 19 recordsLinked to original sources

Use of antimicrobial agents during supportive periodontal therapy.

Individual susceptibility to periodontal breakdown involves an interplay of genes, periodontal pathogens and other modulating factors. Anti-infective treatment, which includes oral hygiene measures, mechanical debridement, pharmacologic intervention and surgery, has been shown to be effective in arresting the progression of periodontal disease. Nevertheless, due to the chronic nature of the disease, susceptible individuals who are not maintained in a supervised recall program subsequent to the active treatment phase, show signs of recurrent destruction. Supportive periodontal therapy (SPT) is an integral part of periodontal treatment for patients with history of periodontitis, and is needed to prevent recurrence of disease in susceptible individuals. To prevent re-infection with periodontal pathogens, SPT includes elimination of dental plaque and bacteria from the oral cavity, thereby preventing the recurrence of pathogens into the gingival area. For individuals at risk of developing periodontitis, SPT should combine self-performed and professional anti-infective therapy, using mechanical and pharmacological means. The existing evidence suggests that the adjunctive use of antimicrobial pharmacologic therapy during SPT may enhance the results of mechanical debridement. The use of antimicrobials varies between patients, and is dependent on risk assessment and longitudinal monitoring of the clinical status of the periodontium.

Anti-Bacterial Agents↗

Interferon-gamma deficiency attenuates local P. gingivalis-induced inflammation.

Infection with the periodontal pathogen Porphyromonas gingivalis causes a strong local inflammatory reaction. Using IFNgamma-deficient mice, we tested the hypothesis that the absence of IFNgamma would result in a reduction of the local pro-inflammatory response to P. gingivalis. Cytokine secretion by macrophages from IFNgamma(-/-) animals was significantly attenuated. Addition of IFNgamma restored cytokine secretion. In vivo injection of P. gingivalis into subcutaneous chambers increased the intra-chamber leukocyte counts and TNFalpha and IL-1beta levels. This increase was significantly lower in the IFNgamma(-/-) mice. Local reconstitution of IFNgamma(-/-) mice at the site of inflammation with the IFNgamma gene increased the levels of TNFalpha and decreased the IL-10 levels. Anti-P. gingivalis IgG1 levels, a marker of Th2 response, were higher in immunized IFNgamma(-/-) than in IFNgamma(+/+) mice. The results suggest that lack of IFNgamma reduced the amplitude of the local pro-inflammatory response without decreasing the humoral protective response. The higher IgG1/IgG2a ratio observed supports the possibility of a Th2-dominant response in IFNgamma-deficient animals.

Animals↗

Immunization to Porphyromonas gingivalis enhances the local pro-inflammatory response to subcutaneous bacterial challenge.

BACKGROUND, AIMS: Human and animal studies have suggested that immunization to P. gingivalis might be beneficial for controlling periodontitis, by the induction of protective antibody response. The present study was designed to examine the effect of immunization on the local cellular, cytokine and antibody response to P. gingivalis in mice. METHODS: Subcutaneous chambers were implanted in 3 groups of mice. 2 groups were then immunized with P. gingivalis in either incomplete Freund's (IFA) or an Alum-based adjuvant. The 3rd group served as the control. At baseline, all mice were challenged with an intra-chamber injection of P. gingivalis. Chamber exudates were sampled at baseline, 1 and 7 days post-challenge, following by determination of leukocyte counts and the cytokines TNF-alpha, IFNgamma (pro-inflammatory) and IL-10 (anti-inflammatory). IgG levels to P. gingivalis were analyzed in both the exudates and serum. RESULTS: Leukocyte accumulation increased in the chambers over the study period and was more marked in the immunized groups. P. gingivalis challenge induced the expression of the tested cytokines in all groups. Levels of IFNgamma showed a significantly greater increase in the immunized groups on day 1 post-challenge. By day 7, the levels in the controls had reached those of the immunized groups. IL-10 levels were significantly higher in the control group compared to the immunized groups on day 1 and by day 7 they were reduced significantly in all groups to barely detectable levels. While there were no significant differences in TNF-alpha levels between IFA and control groups, they were significantly higher in the Alum group on day 0 and 7. Both immunization protocols induced anti-P. gingivalis IgG. The Alum group achieved the highest antibody levels, which were due to the increased expression of IgG1, a marker of a Th2-response. CONCLUSIONS: The results suggest that immunization to P. gingivalis results in enhanced expression of pro-inflammatory, tissue-destructive cytokines in the inflammatory site. The nature of the adjuvant used for immunization allows manipulation of the T-cell response, and alum was more effective in reducing the inflammatory response than IFA.

Adjuvants, Immunologic↗

Genetic polymorphism of the tumor necrosis factor (TNF)-alpha promoter region in families with localized early-onset periodontitis.

Tumor necrosis factor (TNF)-alpha is a potent proinflammatory cytokine that is able to induce tissue destruction and bone resorption. A G-to-A polymorphism at the -308 position of the TNF-alpha promoter region was suggested to influence TNF-alpha production. We had previously shown that monocytes of patients with localized early-onset periodontitis (EOP) secrete high levels of TNF-alpha compared to matched controls. The aim of the present study was to investigate the possible link between the -308 polymorphism in the TNF-alpha gene and EOP. Genomic DNA was extracted from the blood of 64 individuals from 11 nuclear families with EOP. The TNF-alpha polymorphism at -308 was assessed using allele-specific polymerase chain reaction. 77% of the tested adolescents were found to have the G/G genotype, and 23% had the A/G genotype. In the diseased subjects, 81% were with G/G genotype and 19% with A/G genotype. The healthy children had 74% G/G genotype, while 26% had A/G genotype. The differences between the disease group and the healthy group were not statistically significant. In summary, the present results could not demonstrate any link between EOP and genetic polymorphism in the -308 position of the TNF-alpha promoter.

Adenine↗

[Preliminary results of short-term follow-up after MIS screw-type implants with rough surface].

The present article describes the preliminary results of a short-term follow up retrospective study of 104 external hex, screw-type MIS implants with rough surface that were consecutively implanted in 34 patients. The implants were followed up between 1 to 3 years. 49 implants were placed in the maxilla and 55 in the mandible. Bone regenerative procedures were carried out simultaneously in the time of implant placement in 21 of the implants. A total of 6 implants failed (5.7%) during the observation period, all in the first year after implant placement. Two implants failed in the same diabetic patient, and one in a heavy smoker. Two of the failed implants were placed together with bone regenerative procedures, and another one was with no initial stability at the time of implant placement. This short-term follow up report has shown that the success rate of MIS screw-type implants with rough surface is similar to the success rate reported for other implant systems. However, long-term follow up is needed to verify the long-term success MIS implant system.

Bone Regeneration↗

[Single-stage implants in areas of maxillary sinuses that were augmented with allograft. Case reports].

Demineralized freezed dried bone allograft (DFDBA) is known as a bone inductive material, and used widely in periodontal and bone regeneration procedures. DFDBA can also be used for sinus floor augmentation prior or with implant placement. The present manuscript described cases of single-stage implants that were used successfully in areas where the maxillary sinus was augmented with DFDBA simultaneously with implant placement (Case 1) or in a second procedure, 18 months following grafting of the sinus (Case 2). These cases demonstrated the ability to use single-stage implants in the augmented maxillary sinus, in a separated or simultaneous procedure.

Bone Regeneration↗

Repeat bacterial challenge in a subcutaneous chamber model results in augmented tumour necrosis factor-alpha and interferon-gamma response, and suppression of interleukin-10.

The present study compared the effect of a single or a repeat challenge with the Gram-negative pathogen Porphyromonas gingivalis on the local inflammatory response within subcutaneous chamber model in mice. Subcutaneous chambers were implanted 2 weeks prior to the final challenge. The repeat-challenge (REP) group received two intrachamber bacterial injections 14 days apart, while the single-injection group (SIN) received only a single bacterial challenge. Injection of saline was used as the control. The cellular contents of the chamber exudates were used for differential cell counts, and the supernatants were analysed for tumour necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin (IL)-10 levels. Immunoglobulin G1 (IgG1) and IgG2a levels to P. gingivalis in the exudates were also determined. The results showed that the leucocyte counts increased significantly post-challenge, and the REP group showed the highest number of lymphocytes and neutrophils. Both P. gingivalis-challenged groups exhibited significant increase in TNF-alpha and IL-10 levels at day 1 post-challenge. TNF-alpha levels in the chamber exudate were threefold higher in the REP group compared with the SIN group on day 1 post-challenge (P < 0.05). In contrast, IL-10 levels were significantly lower in the REP group 1 day post-challenge compared with the SIN group. The REP group had significantly higher levels of IFN-gamma at baseline, and this difference remained significant 1 day post-challenge. Analysis of antibody levels to P. gingivalis showed that while the control and the SIN groups had no anti-P. gingivalis IgG in the chamber exudate during the 7-day study period, the REP group showed high anti-P. gingivalis IgG levels. In addition, the titres of IgG2a were fivefold higher than the IgG1 titres. The results showed that a repeat local challenge with P. gingivalis augmented the proinflammatory cytokines TNF-alpha and IFN-gamma, while inhibiting the accumulation of the anti-inflammatory cytokine IL-10. This shift towards a T helper 1 (Th1)-dominant response was reflected in the relatively high anti-P. gingivalis IgG2a titres in the local inflammatory environment 7 days post-challenge.

Animals↗

Haim-Munk syndrome and Papillon-Lefèvre syndrome are allelic mutations in cathepsin C.

Of the many palmoplantar keratoderma (PPK) conditions, only Papillon-Lefèvre syndrome (PLS) and Haim-Munk syndrome (HMS) are associated with premature periodontal destruction. Although both PLS and HMS share the cardinal features of PPK and severe periodontitis, a number of additional findings are reported in HMS including arachnodactyly, acro-osteolysis, atrophic changes of the nails, and a radiographic deformity of the fingers. While PLS cases have been identified throughout the world, HMS has only been described among descendants of a religious isolate originally from Cochin, India. Parental consanguinity is a characteristic of many cases of both conditions. Although autosomal recessive transmission of PLS is evident, a more "complex" autosomal recessive pattern of inheritance with phenotypic influences from a closely linked modifying locus has been hypothesised for HMS. Recently, mutations of the cathepsin C gene have been identified as the underlying genetic defect in PLS. To determine if a cathepsin C mutation is also responsible for HMS, we sequenced the gene in affected and unaffected subjects from the Cochin isolate in which both the PLS and HMS phenotypes appear. Here we report identification of a mutation of cathepsin C (exon 6, 2127A--> G) that changes a highly conserved amino acid in the cathepsin C peptide. This mutation segregates with HMS in four nuclear families. Additionally, the existence of a shared common haplotype for genetic loci flanking the cathepsin C gene suggests that affected subjects descended from the Cochin isolate are homozygous for a mutation inherited "identical by descent" from a common ancestor. This finding supports simple autosomal recessive inheritance for HMS in these families. We also report a mutation of the same exon 6 CTSC codon (2126C-->T) in a Turkish family with classical PLS. These findings provide evidence that PLS and HMS are allelic variants of cathepsin C gene mutations.

Alleles↗

The interactions of human neutrophils with the constituents of an experimental dental biofilm.

Despite the antibacterial properties of neutrophils, their ability to prevent colonization of the dental biofilm by pathogenic bacteria is limited. The present study examined the ability of human neutrophils to attach to an experimental dental biofilm and tested their antibacterial functions following adhesion. Neutrophil adhesion was greatest to hydroxyapatite (HA) in the absence of biofilm. Among the biofilms, glucosyltransferase or fructosyltransferase adsorbed onto saliva-coated HA showed the highest adhesion of cells. The adhesion of neutrophils was directly related to their initial concentration in the solution and to the duration of incubation. Plasma was found to reduce neutrophil attachment significantly, while stimulation of the cells had no effect. Stimulation of attached neutrophils induced superoxide secretion with levels significantly lower than that secreted by suspended cells. The presence of neutrophils on the biofilm reduced the number and the viability of Streptococcus mutans attached to the beads. The present findings suggest that neutrophils are able to attach to dental biofilms and that the attached neutrophils retained their antibacterial activity.

Adult↗

Experimental stress suppresses recruitment of macrophages but enhanced their P. gingivalis LPS-stimulated secretion of nitric oxide.

BACKGROUND: Epidemiological studies have suggested that stress can alter the onset and progression of periodontal disease. However, the mechanisms involved are not clear. The present study was designed to examine whether the functional response of mouse macrophages stimulated by Porphyromonas gingivalis lipopolysaccharide (LPS) is affected by experimental stress, and to investigate the role of corticosterone (CS) in the stress-related effects. METHODS: Two models of stress were used: emotional (isolation) and physical (cold). We measured thioglycollate-induced macrophage recruitment in vivo, and LPS-induced nitric oxide (NO) secretion by the macrophages in vitro. Two groups of mice were exposed to the stress conditions: isolation or cold. A third group was injected daily with CS, and a fourth group was used as a control (no stress). After 3 days of stress conditions, thioglycollate was injected into the peritoneal cavity. Four days later, peritoneal macrophages were isolated, counted, and cultured. The secretion of NO by the cultured cells was evaluated with and without P. gingivalis LPS stimulation. RESULTS: The number of cells in the peritoneal lavage of stressed mice was significantly reduced in comparison to macrophages isolated from non-stressed animals. The number of macrophages from CS-treated mice did not differ from controls. NO secretion from unstimulated macrophages did not differ between the stressed and control groups. Stimulation of the macrophages with P. gingivalis LPS significantly enhanced NO secretion by macrophages from the control and stressed animals, but not by the CS-treated group. NO levels secreted by P. gingivalis-stimulated cells from the two stressed groups were significantly higher than the levels secreted by controls, and the isolation group released significantly higher levels than the cold group. Stimulation of the macrophages with P. gingivalis LPS and interferon (IFN)-gamma resulted in enhanced NO secretion in the 4 groups compared to LPS alone, with no significant differences between the groups. CONCLUSIONS: The results suggest that experimental stress modulates the response of macrophages to inflammatory stimulants, and that CS is not the sole mediator involved. The presence of IFN-gamma in the culture may mask the functional differences induced by stress. The stress-induced upregulation of NO secretion might be involved in the accelerated periodontal destruction in stressed subjects.

Analysis of Variance↗

Using the PerioChip in treating adult periodontitis: an interim report.

Multicenter clinical trials have established that the adjunctive use of the subgingival controlled release of chlorhexidine, in the form of the PerioChip, significantly reduces pocket probing depth, improves probing attachment levels, and reduces bleeding on probing compared to scaling and root planing alone, for periods up to 9 months. The purpose of the present study was to report on the adjunctive use of the PerioChip for the long-term management of adult periodontitis for 2 years. A total of 836 patients with adult periodontitis from private dental offices were recruited into the trial. This interim report is on the first 72 patients to have completed the 2-year study. Treatments included initial definitive therapy followed by PerioChip placement in pocket sites with a pocket probing depth of > or = 5 mm after 1 month. Subsequently, the patients received routine periodontal maintenance therapy together with the placement of a PerioChip in pockets with pocket probing depths > or = 5 mm every 3 months. Results indicated that there was a continuous decrease in pocket probing depth over the 2 years (1.26 +/- 0.77 mm). This decrease in pocket probing depth was marked over the first 9 to 12 months, and then appeared to be less marked over the next 12 months. At 2 years, 60% of the patients had at least 2 pockets showing a reduction of 2 mm or more, and only 10% of the patients showed no change or increased pocket probing depth. The results indicate that adjunctive PerioChip use is a clinically effective treatment option for dental professionals and their patients for the long-term management of adult periodontitis.

Adult↗

The effect of extracellular polysaccharides from Streptococcus mutans on the bactericidal activity of human neutrophils.

Extracellular polysaccharides (PS) synthesized by oral bacteria constitute one of their major virulence factors. The PS, synthesized from sucrose, facilitate adhesion and colonization by bacteria to tooth surfaces. The study was designed to test the effect of in situ production of extracellular PS by Streptococcus mutans on the bactericidal activity of human neutrophils. These effects were tested on bacteria pre-exposed to sucrose (PS-positive Strep. mutans) and compared to bacteria not exposed to sucrose (PS-negative Strep. mutans). The interactions between neutrophils and Strep. mutans were tested in suspension and on bacteria in an experimental model of dental plaque. Viability of Strep. mutans was measured by [3H]-thymidine incorporation into the bacteria. Degranulation of neutrophils was evaluated by the release of lysozyme, and the production of reactive oxygen products was measured by chemiluminescence. When neutrophils were incubated with suspended bacteria, the viability of PS-negative Strep. mutans was 20% of that of bacteria not incubated with neutrophils (control), while the viability of PS-positive Strep. mutans was 40% of the control. In the experimental dental-plaque model, 50% of the PS-negative Strep. mutans were killed by neutrophils while the viability of PS-positive Strep. mutans was not different than of the control. Degranulation of neutrophils was not affected by the presence of extracellular PS of Strep. mutans. Artificial stimulation of neutrophils with phorbol myristate acetate also did not enhance the bactericidal effect of neutrophils on PS-positive Strep. mutans. However, PS-positive Strep. mutans elicited oxygen-reactive products from neutrophils, 2-fold less than with PS-negative Strep. mutans. The results indicate that in situ production of bacterial extracellular polysaccharides might be a major virulence factor of Strep. mutans, enabling PS-positive Strep. mutans in the dental-plaque biofilm to evade killing by human neutrophils.

Anti-Bacterial Agents↗

A laboratory assessment of enamel hypoplasia of teeth with varying severities of dental fluorosis.

The effect of lifelong exposure to drinking-water containing fluoride on tooth enamel microhardness was investigated. Dental fluorosis of teeth from adult subjects, who lived continuously since birth in areas characterized by the hot climate of India, supplied by drinking-water containing between 0.5 and 8.7 parts/10 F, was estimated by the Dean score. Tooth enamel sections were examined from the enamel surface towards the dentino-enamel junction (DEJ) for microhardness. Separated enamel crowns were pulverized and analysed for fluoride. Regarding the distribution of the fluoride concentrations in the drinking-water, we selected a partition below and above 0.8 parts/10 F as a criterion for comparison between the results. Tooth enamel of humans from Israel living in a drinking-water area containing about 0.5 parts/10 F was also examined. Positive associations were evident between fluoride in drinking-water, fluoride concentrations in the bulk enamel and fluorosis selection. A significantly high inverse relationship was evident between the fluoride concentration of the drinking-water and the subsurface enamel microhardness. In similar fluoride-concentration drinking-water areas of India and Israel the microhardness of the subsurface enamel was less for the Indian teeth. The microhardness of the enamel near the DEJ for the three different water fluoride-concentration areas was not significantly different.

Adult↗

Differentiation of monocytes to macrophages primes cells for lipopolysaccharide stimulation via accumulation of cytoplasmic nuclear factor kappaB.

During infection, circulating blood monocytes migrate from the vasculature to the extravascular compartments where they mature into tissue macrophages. The maturation process prepares the cell to actively participate in the inflammatory and the immune responses, and many transcription factors have been found to be involved. Here we report on a novel role for nuclear factor kappaB (NF-kappaB) in this process. Its accumulation in the cytoplasm of differentiated macrophages is responsible for the enhanced ability of the cell to respond to lipopolysaccharide (LPS) stimulation, as determined by tumor necrosis factor alpha (TNF-alpha) secretion. Differentiation of the human monocytic cell line THP-1 into macrophage-like cells was induced by exposure of the cells to phorbol myristate acetate. DNA-bindable NF-kappaB was not detected in the cytoplasm of undifferentiated THP-1 cells but accumulated in the cytoplasm of the cells following differentiation. No TNF-alpha was detected in the media of resting differentiated and nondifferentiated THP-1 cells. Stimulation with LPS of differentiated cells induced the production of higher levels of TNF-alpha than stimulation of nondifferentiated cells. This hyperresponsiveness to LPS was found in the mRNA and secreted TNF-alpha levels. Furthermore, stimulation with LPS induced the translocation of NF-kappaB from the cytoplasm into the nucleus. This translocation process was more rapid in the differentiated cells than in the nondifferentiated cells, and the resultant accumulated levels of NF-kappaB in the nucleus were higher. The DNA-bindable NF-kappaB was identified as a heterodimer of p65 and p50. The results suggest that NF-kappaB accumulation in the cytoplasm during maturation of monocytes to macrophages primes the cells for enhanced responsiveness to LPS and results in the rapid secretion of inflammatory mediators, such as TNF-alpha, by mature macrophages following LPS challenge.

Cell Differentiation↗

Activation of murine macrophages by lipoprotein and lipooligosaccharide of Treponema denticola.

We have recently demonstrated that the periodontopathogenic oral spirochete Treponema denticola possesses membrane-associated lipoproteins in addition to lipooligosaccharide (LOS). The aim of the present study was to test the potential of these oral spirochetal components to induce the production of inflammatory mediators by human macrophages, which in turn may stimulate tissue breakdown as observed in periodontal diseases. An enriched lipoprotein fraction (dLPP) from T. denticola ATCC 35404 obtained upon extraction of the treponemes with Triton X-114 was found to stimulate the production of nitric oxide (NO), tumor necrosis factor alpha (TNF-alpha), and interleukin-1 (IL-1) by mouse macrophages in a dose-dependent manner. Induction of NO by dLPP was at 25% of the levels obtained by Salmonella typhosa lipopolysaccharide (LPS) at similar concentrations, while IL-1 was produced at similar levels by both inducers. dLPP-mediated macrophage activation was unaffected by amounts of polymyxin B that neutralized the induction produced by S. typhosa LPS. dLPP also induced NO and TNF-alpha secretion from macrophages isolated from endotoxin-unresponsive C3H/HeJ mice to an extent similar to the stimulation produced in endotoxin-responsive mice. Purified T. denticola LOS also produced a concentration-dependent activation of NO and TNF-alpha in LPS-responsive and -nonresponsive mouse macrophages. However, macrophage activation by LOS was inhibited by polymyxin B. These results suggest that T. denticola lipoproteins and LOS may play a role in the inflammatory processes that characterize periodontal diseases.

Animals↗

The effect of stress on the inflammatory response to Porphyromonas gingivalis in a mouse subcutaneous chamber model.

BACKGROUND: The impact of emotional stress on the outcome of infectious diseases was studied in animal models and humans, but data related to the effect of stress on periodontal infection are limited. Using the subcutaneous chamber model in mice, the present study was carried out to investigate the effect of stress on the host response to Porphyromonas gingivalis. METHODS: Mice with subcutaneous chambers (2 per animal) were divided into 4 treatment groups: cold-stress; isolation-stress; corticosterone (CS)-injected; and controls. On the third day of stress conditions, heat-killed P. gingivalis were injected into the chambers. The chambers were sampled 1 and 5 days later and analyzed for leukocyte number, tumor necrosis factor (TNF)-alpha levels, and interferon (IFN)-gamma levels. RESULTS: Injection of P. gingivalis induced the migration of leukocytes into the chambers and increased the intrachamber levels of IFN-gamma and TNF-alpha. There were no significant differences in cell number and IFN-gamma levels between the different treatment groups, but the levels of TNF-alpha were significantly lower in the isolation-stress and cold-stress groups compared to control animals. CS-injected animals were not different from controls. In addition, the levels of TNF-alpha in the stressed animals were lower on the fifth day post-injection than on the first day, but not in the CS and control group. CONCLUSIONS: The results suggest that the levels of TNF-alpha induced by P. gingivalis in the infection site are downregulated in stressed animals, and CS is not the sole mediator responsible. The stress-induced reduction in TNF-alpha levels might have an impact on the pathogenesis of periodontal disease in humans experiencing emotional stress.

Animals↗

Effect of amine fluoride-stannous fluoride containing toothpaste (Meridol) on plaque and gingivitis in adults: a six-month clinical study.

Treatments that aim to reduce the accumulation of bacteria on dental surfaces are considered today as the most efficient way of treating gingivitis and the resultant destruction of periodontal tissues. Mechanical plaque removal was found to be very effective in the control of gingival inflammation for most patients, but the supplement of toothpastes and mouthwashes with anti-plaque properties may benefit individuals with unperfected plaque control. The aim of the present study was to investigate the long-term effect of amine fluoride/stannous fluoride (AmF/SnF2) toothpaste on plaque levels and gingivitis in adults, as an additional measure to standard oral hygiene. One hundred and three adult subjects with gingivitis were divided into two randomised groups. One group used NaF toothpaste (control) and the second group AmF/SnF2 (Meridol) toothpaste. The subjects were examined every two months under double-blind conditions. The recorded parameters were plaque index (PlI), gingival index (GI) and bleeding on probing. The differences in PlI between baseline and the end of the study were statistically significant for both treatments, and no significant differences were found between the two treatment groups. There was a significant drop in GI between baseline and the concluding examination only for the AmF/SnF2 group, but the differences between the two treatment groups were not significant. A significant reduction in the percentage of bleeding sites during the six-month study period was found in the AmF/SnF2 group, but not in the control group. The results of the present study suggest that the long-term use of AmF/SnF2 toothpaste in adults may be of benefit to gingival health.

Adult↗

In vivo exposure to Porphyromonas gingivalis up-regulates nitric oxide but suppresses tumour necrosis factor-alpha production by cultured macrophages.

The present study was designed to test whether the functional response of mouse macrophages elicited by chronic exposure to bacteria will be different from that of cells elicited by a non-bacterial irritant. Macrophage elicitation was conducted by Porphyromonas gingivalis, a major periodontal pathogen, in comparison to a standard elicitation by thioglycollate (TG). We measured lipopolysaccharide (LPS)-induced nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) secretion by the elicited macrophages, and the expression of inflammatory cytokines in the whole elicited cell population. In addition, we tested the response of TG-elicited macrophages to pretreatment with P. gingivalis LPS in vitro. Mouse peritoneal macrophages were harvested 4 days after intraperitoneal injection of TG or heat-killed P. gingivalis. TG-elicited macrophages produced undetectable levels of TNF-alpha and approximately 0.5 microM of NO. The stimulation of the macrophages with LPS resulted in the secretion of NO and TNF-alpha in a dose-dependent manner. The P. gingivalis-elicited macrophages produced basal levels of approximately 5 microM NO, but TNF-alpha was not detectable. LPS stimulation of these cells further increased the secretion of NO eightfold while TNF-alpha remained undetectable. The NO secretion by P. gingivalis-elicited cells was significantly higher than that by TG-elicited cells. Examination of cytokine expression in the whole elicited cell population revealed that both P. gingivalis-elicited cells and TG-elicited cells expressed messenger RNA for interleukin-2 (IL-2), TNF-alpha and interferon-gamma (IFN-gamma), but not for IL-4. IL-6 was expressed in P. gingivalis-elicited cells only. Pretreatment of TG-elicited macrophages with P. gingivalis LPS for 24 hr prior to a second LPS challenge resulted in down-regulation of TNF-alpha secretion and up-regulation of NO secretion, a response similar to that seen in P. gingivalis-elicited peritoneal macrophages. The results suggest that the in vivo exposure of resident macrophages to P. gingivalis induces functional changes in peritoneal macrophages. These changes might be due to the effect of P. gingivalis LPS.

Animals↗