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Real-time PCR quantification of cytomegalovirus in aggressive periodontitis lesions using TaqMan technology.

BACKGROUND: Herpesviruses are implicated in the pathogenesis of human periodontitis. However, the quantity of herpesviruses in periodontal sites remains unknown. OBJECTIVE: The aim of this study was to compare levels of subgingival human cytomegalovirus (HCMV) in aggressive periodontitis patients and in periodontally healthy subjects. METHODS: A total of 16 consecutive subjects with aggressive periodontitis and 15 healthy control subjects were included in the study. Subgingival specimens were collected by a periodontal curette. TaqMan real-time polymerase chain reaction (PCR) assay was used to quantify HCMV. RESULTS: HCMV was detected in 68.8% of aggressive periodontitis lesions but not in any of the periodontally healthy study sites. HCMV viral load in positive subgingival specimens ranged from 5 x 10(2) to 7.4 x 10(3) copies/ml. CONCLUSIONS: The TaqMan real-time PCR technology seems to provide a rapid and sensitive method for quantifying HCMV in periodontal pockets. The present findings confirm the frequent presence of HCMV in aggressive periodontitis lesions. Determining HCMV levels in different types of periodontitis may help elucidate the periodontopathic role of the virus and advance our understanding of the disease pathogenesis.

Adolescent↗

Periodontal disease in American Indians and Alaska Natives.

OBJECTIVE: The primary purpose of this paper is to provide information on the periodontal disease status of Native Americans using a variety of data sources. The impact of periodontal disease on the provision of dental care within the Indian Health Service (IHS) is also discussed. METHODS: Four data sources were used to evaluate the periodontal disease status of Native Americans: IHS periodontal disease monitoring system (1962-78), 1984 IHS Patient Oral Health Survey, 1990 WHO community-based survey (ICS-II), and the 1991 IHS Patient Oral Health Survey. RESULTS: There appears to be a trend toward a higher prevalence of incipient and overt periodontal disease among Native Americans over time. The prevalence of overt periodontal disease (periodontal pockets > 5.5 mm) is higher among Native American diabetic patients than nondiabetic patients (34% vs 19%). CONCLUSIONS: Due to the variety of indices used by the IHS during the last 20 years, it is difficult to make direct comparisons of the available periodontal disease data. However, it appears that the prevalence of periodontal disease among Native Americans is increasing. Type II diabetes accounts for significant increases in periodontal disease and tooth loss in Native American populations. Certain forms of early onset periodontal disease also may pose significant threats to the oral health of Native Americans.

Adult↗

Epidemiology of periodontal disease: a review and clinical perspectives.

The purpose of this paper is to assimilate epidemiological evidence for the prevalence of periodontal disease in human populations, and for comprehensive understanding of the disease for health care providers. Periodontal disease is a pathological condition affecting the supporting structures of teeth. It is characterised by a bacterial challenge that can instigate a destructive host response leading to periodontal attachment loss, bone loss and ultimately, possible tooth loss. The specifics of the disease process are obscured by our incomplete understanding of the role of various risk factors. Periodontal epidemiology literature lacks consistency in methodology of research, which includes various definitions for periodontal disease and health; different approaches to measuring periodontal indices of pocket depth, and attachment loss; inconsistent study designs and lack of adjustments to known risk factors. These inconsistencies do not allow for effective comparison of epidemiological studies, which is essential to find strong associations of risk factors with periodontal disease, which in turn is necessary for the interpretation of risk and causality. This paper will address several areas within the topic of periodontal disease epidemiology, including definitions of periodontal disease instituted by researchers, approaches to epidemiological studies in periodontitis, and risk factors in periodontal disease. Consideration is given to aspects of design and analyses relevant to evaluation of reports in the literature. For the clinical practitioner this review provides a theoretical framework to approach patients with comprehensive knowledge of not only the disease presentation, but also the environmental factors that govern past history, present condition and future response to treatments and interventions.

Alveolar Bone Loss↗

Transplantation of labeled periodontal ligament cells promotes regeneration of alveolar bone.

Regeneration of damaged periodontal tissues is mediated by periodontal cells, but a major sub-population comprises highly differentiated cells that do not renew. To overcome the loss of specialized cell types caused by disease, various therapeutic approaches including cell transplants have been developed to promote cell re-population in periodontal tissues. As previous transplantation studies used unlabeled cells, that are indistinguishable from host cells, it has been difficult to assess the contributions of transplanted cells to the healing processes. To track the fate and differentiation of rat periodontal cells transplanted into periodontal wounds, we used collagen-coated fluorescent beads as a permanent endocytosed marker, or cells constitutively expressing beta-galactosidase. We assessed osteogenic cell differentiation with immunohistochemical staining for osteopontin and bone sialoprotein. Cells were transplanted into periodontal wounds created in Sprague--Dawley male rats that are null for beta-galactosidase. Defects were allowed to heal spontaneously (controls), or were closed with collagen implants mixed with beta-galactosidase-positive (Lac-Z) periodontal cells, or closed with collagen implants mixed with periodontal cells loaded with fluorescent beads. Animals were killed at 1 and 2 weeks after surgery and tissues were prepared for morphometric assessment and immunostaining for osteopontin (OPN) and bone sialoprotein (BSP). Transplanted cells were easily distinguished by fluorescent beads or by beta-galactosidase-positive expression and were distributed throughout the regenerating periodontal ligament (PL) and alveolar bone. At 1 week after wounding, animals treated with beta-galactosidase-positive cells exhibited a slightly higher percentage of labeled cells in the PL compared with the fluorescent bead-labeled cell implant group (2% vs. 1% respectively; P > 0.2). At Week 2 percentages of labeled cells were slightly increased in the regenerating PL (approximately 3% for both groups, P > 0.2). In regenerating alveolar bone at 1 week, animals that were treated with beta-galactosidase-positive cells and fluorescent bead-loaded cells exhibited approximately 30% and 25% of labeled cells respectively. At 2 weeks after wounding there was an increase in the percentage of transplanted beta-galactosidase-positive cells (approximately 39% at week 2; P < 0.05), but not of transplanted cells with fluorescent beads (approximately 25% at week 2). In sites with transplanted cells there were higher percentages of OPN positive and BSP positive cells in nascent bone and more newly formed bone than in controls (>40%; P < 0.05). Transplantation of beta-galactosidase-positive cells or cells loaded with fluorescent beads is a useful method for assessing the fate and differentiation of periodontal cells in vivo. Fluorescent beads, however, are diluted at mitosis and this method underestimates the percentage of transplanted cells. As transplanted periodontal cells in both groups promoted regeneration of alveolar bone, cell transplantation could improve the restoration of periodontium destroyed by periodontitis.

Alveolar Bone Loss↗

Serum IgG reactivity to subgingival bacteria in initial periodontitis, gingivitis and healthy subjects.

BACKGROUND/AIMS: Established periodontal diseases may be associated with antibody responses to periodontal pathogens, but it is not known at which stage of disease this antibody response is initiated. This study aimed to characterize the host systemic response in initial periodontitis, gingivitis, and periodontal health, to evaluate whether elevated serum antibodies to subgingival species could be detected in initial periodontitis. METHOD: Human systemic immune response were evaluated to 40 subgingival bacterial species in 16 healthy, 21 gingivitis, 11 initial periodontitis and 5 progressing recession adults. Subjects had minimal periodontal attachment level (AL) loss at baseline. Disease categories were determined after 12 months monitoring at three-month intervals. Increased AL loss > or = 1.5 mm (disease activity) at interproximal sites defined initial periodontitis, recession was characterized by AL loss at buccal sites. Serum IgG antibodies were evaluated semi-quantitatively by immunoblot from blood taken at baseline, active and final visits. RESULTS: No antibody was detected from 55% of reactions. When detected, levels were below those reported for advanced periodontitis subjects. There were no major differences in serum antibody levels between healthy, gingivitis and initial periodontitis subjects, despite differences in the subgingival microbiota. Serum antibodies for more species were detected in recession subjects, compared with the other study subjects. No changes in antibody levels were detected between baseline, active, and final visits. No systematic association between species colonization and presence of systemic antibody was observed. CONCLUSIONS: This study did not detect differential elevation of mean serum antibody levels in initial periodontitis subjects, suggesting that serum antibody levels are not sensitive risk markers for initial periodontitis.

Adult↗

Herpesviruses in HIV-periodontitis.

BACKGROUND/AIMS: Human herpesvirus-associated diseases exhibit elevated morbidity and mortality in patients infected with human immunodeficiency virus (HIV). This study aimed to investigate the occurrence of herpesviruses in HIV-periodontitis. METHOD: Gingival biopsies from periodontitis lesions of 21 HIV-patients and 14 non HIV-patients were studied. Nested-polymerase chain reaction methods were employed to detect human cytomegalovirus, Epstein-Barr virus type 1 and 2 (EBV-1, EBV-2), herpes simplex virus, human herpes virus (HHV)-6, HHV-7 and HHV-8. RESULTS: Gingival biopsies from HIV-periodontitis lesions showed on average 4.0 herpesvirus species and gingival biopsies from HIV periodontitis lesions of non-HIV patients revealed an average of 1.9 herpesvirus species (p<0.001). Occurrence of 4 to 6 different herpesviruses was more common in HIV- than in non HIV-gingival biopsies (71% vs. 7%) (p<0.001). EVB-2 was detected in 12 (57%) biopsies from HIV-periodontitis but was absent in non HIV-periodontitis biopsies (p= 0.002). HHV-6 also occurred in significantly higher frequency in HIV-periodontitis (71%) than in non HIV-periodontitis (21%) (p=0.01). HHV-8 was detected only in biopsies from HIV-periodontitis lesions.. CONCLUSION: HIV-periodontitis seems to be associated with elevated occurrence of EBV-2, HHV-6 and herpesvirus co-infections compared to periodontitis in non-HIV-patients. The periodontopathic significance of herpesviruses in HIV-periodontitis constitutes a research topic of considerable interest.

AIDS-Related Opportunistic Infections↗

Changes in vasoactive intestinal peptide in gingival crevicular fluid in response to periodontal treatment.

AIMS: To evaluate the role of the anti-inflammatory neuropeptide vasoactive intestinal peptide (VIP) in periodontal health and disease and to determine the effects of periodontal treatment, resulting in a return to periodontal health, on the levels of VIP in gingival crevicular fluid (GCF). METHODS: At baseline, 10 subjects with periodontitis (nine females, one male, mean age 43.0, SD 7.3) started a course of non-surgical periodontal treatment. Clinical indices were measured at one periodontitis and one clinically healthy site at an initial visit and at 8 weeks after the completion of treatment in each subject. A 30-s sample of GCF was collected from each test site using perio paper strips. The volume of GCF was measured and each sample subsequently analysed for VIP by radioimmunoassay. One healthy site was sampled from each member of a control group (10 females, mean age 29.9, SD 8.2 years) with clinically healthy gingiva and no periodontitis. RESULTS: The clinical condition of all periodontitis sites improved as a result of periodontal treatment. The levels of VIP (pg/30 s sample) in periodontitis-affected sites fell significantly from 302.0 (SD 181.2) at the initial visit to 78.0 (54.4) after treatment, p = 0.007. The reduction in the concentration of VIP (pg/ micro L) in GCF from 524.3 (322.3) to 280.8 (280.2) was not statistically significant. The levels of VIP in clinically healthy sites fell from 115.5.5 (74.3) to 77.8 (32.3), n.s. and the concentration changed little from 883.8 (652.1) to 628.7 (323.3), n.s. There were substantially smaller amounts of VIP (25.8, SD 12.8) pg in healthy sites sampled from control subjects. CONCLUSIONS: VIP is present in GCF in greater quantities in periodontitis-affected than clinically healthy sites. In addition, the reduction in inflammation resulting from effective periodontal treatment is associated with a reduction in the levels of VIP in gingival crevicular fluid.

Adult↗

Effective, safe, practical and affordable periodontal antimicrobial therapy: where are we going, and are we there yet?

Several important trends are noticeable in the management of periodontal disease. Searching for specific risk factors for periodontal disease permits therapy planning with the intention of doing less for low-risk patients and increasing the preventive and therapeutic modalities for high-risk patients. Also, significant progress in the area of chemotherapeutic development enables dentists to increase the number of periodontitis patients receiving nondisruptive antimicrobial therapy and decreases the need for surgical treatment. Use of anti-infective chemotherapeutic and antibiotic agents has become a specialized and increasingly effective means of preventing and treating destructive periodontal disease. Local care, including subgingival application of some type of antiseptics, is widely accepted. The use of systemic antibiotics is not routine and should be reserved for aggressive and refractory periodontal infections. In general, it is better to be thoroughly familiar with a limited number of drugs and treatment methods and use them properly than to try to master a plethora of antimicrobial therapies. Combating periodontal infections is best accomplished by combined mechanical and chemotherapeutic efforts of the dental professional and the patient. The trend during recent years has been to treat periodontal infections aggressively, employing short-course antimicrobial therapy using a battery of safe and affordable antimicrobial agents, each exhibiting high activity against various periodontal pathogens and administered in ways to concurrently affect pathogens residing in different oral ecological niches, followed by regular maintenance visits having a strong anti-infective emphasis. At the beginning of therapy, patients should be assigned self-help tasks having maximal antimicrobial effectiveness, with a focus on control of the subgingival periodontopathic microbiota. When patients see positive clinical results from their daily oral hygiene efforts, they are motivated to remain active participants in managing their periodontal condition. This article emphasizes anti-infective periodontal therapies that are effective and, when properly administered, are essentially nontoxic; are widely available around the world to dentists as well as to patients; and are acceptable to most patients in terms of methods of application, supporting oral hygiene efforts and financial costs. We believe that, with improved knowledge of the periodontopathic microbiota, with the availability of microbiological tests to identify periodontal pathogens and optimal therapy, with various safe and affordable yet effective antimicrobial agents and therapies and, eventually, with the development of one or more effective vaccines, the future looks very bright for patients at risk for or suffering from destructive periodontal disease.

Anti-Bacterial Agents↗

Does periodontitis reflect inflammation and malnutrition status in hemodialysis patients?

BACKGROUND: Chronic infection and inflammation, including periodontitis, is linked to an increased risk for atherosclerosis. To investigate the possible adverse effects of periodontitis in maintenance hemodialysis patients, we compared periodontal severity with malnutrition and inflammation, which are associated with poor atherosclerotic outcome in hemodialysis patients. METHODS: Two hundred fifty-three hemodialysis patients were included in this study to evaluate clinical periodontal status by using the Plaque Index, Gingival Index, and Periodontal Disease Index. Geographic, hematologic, biochemical, and dialysis-related data also were collected. Values for nutritional and inflammatory markers, such as albumin, blood urea nitrogen, creatinine, transferrin, absolute lymphocyte count, normalized protein catabolic rate, high-sensitivity C-reactive protein, and ferritin, were included for analysis with the Periodontal Index. RESULTS: Poor oral health status was shown by 80.6% of hemodialysis patients with periodontal disease. In an analysis of geographic and disease-related parameters, we found that aging, smoking, diabetes, and longer dialysis duration were associated with severity of periodontitis. Parameters of malnutrition and inflammation also were associated with poor periodontal status. We next conducted multiple regression analysis and found that age, diabetes, smoking, albumin level, and dialysis duration were associated independently with periodontitis severity in hemodialysis patients. According to the severity of periodontitis, there were higher percentiles of patients with malnutrition (chi-square = 13.055; P = 0.005) and inflammation (chi-square = 10.046; P = 0.018) in the severe group. CONCLUSION: Periodontal health is poor in hemodialysis patients and correlates with markers of malnutrition and inflammation. Its diagnosis and treatment deserve better awareness.

Aged↗

Update on human cytomegalovirus in destructive periodontal disease.

AIM: Human cytomegalovirus (HCMV), a herpesvirus, is discussed in this review as it relates to destructive periodontal disease in humans. RESULTS: HCMV genomic sequences, detected by polymerase chain reaction identification, occur with elevated frequency in severe adult periodontitis, localized and generalized aggressive (juvenile) periodontitis, Papillon-Lefèvre syndrome periodontitis, acute necrotizing ulcerative gingivitis, and periodontal abscesses. DISCUSSION: Herpesviruses establish lifelong persistent infections. HCMV infection involves an asymptomatic latent phase interrupted by periods of recrudescence where viral replication and possibly clinical disease become manifest. HCMV reactivation is triggered by a number of immunosuppressive factors, some of which have been shown also to be risk factors/indicators of periodontitis. HCMV periodontal infection may cause release of tissue-destructive cytokines, overgrowth of pathogenic periodontal bacteria, and initiation of cytotoxic or immunopathologic events. CONCLUSIONS: A growing body of data supports the concept that HCMV contributes to severe types of periodontal disease. HCMV infection of the periodontium may alter the immune control of resident microorganisms and be important in a multistage pathogenesis of periodontitis involving viral activation, periodontopathic bacteria, and host immune responses. Understanding the significance of HCMV and other herpesviruses in the development of periodontal disease may have important therapeutic implications. Vaccines against HCMV, which are in various stages of development, need to be evaluated for their ability to decrease the incidence of destructive periodontal disease.

Animals↗

Elevated serum IgG titer and avidity to Actinobacillus actinomycetemcomitans serotype c in Japanese periodontitis patients.

AIM: The purpose of this study was to characterize serum antibody responses to different serotypes of Actinobacillus actinomycetemcomitans strains in various forms of periodontitis and to determine whether any specific type of A. actinomycetemcomitans was associated with any specific form of periodontitis in a Japanese population. METHODS: Sonicated whole cell and autoclaved serotype antigens of A. actinomycetemcomitans were used. Serum IgG titer and avidity to A. actinomycetemcomitans were measured by enzyme-linked immunoabsorbant assay (ELISA) and ammonium thiocyanate-dissociation ELISA, respectively, in 46 aggressive periodontitis patients (8 localized, 38 generalized), 28 chronic periodontitis patients, and 18 periodontally healthy subjects. The presence of A. actinomycetemcomitans in plaque and saliva samples was determined using polymerase chain reaction. RESULTS: Generalized aggressive and chronic periodontitis patients exhibited significantly higher IgG titers than healthy subjects to both sonicated and autoclaved antigens of serotype c strains, while IgG titer to serotype b (Y4) was significantly higher in localized aggressive periodontitis patients compared to healthy subjects. No A. actinomycetemcomitans was detected in localized aggressive periodontitis patients. A. actinomycetemcomitans-positive patients exhibited significantly higher IgG titer and avidity to serotype c than A. actinomycetemcomitans-negative patients. In A. actinomycetemcomitans-positive patients, a significantly positive correlation was observed between antibody titer and avidity to serotype c. A. actinomycetemcomitans-positive patients with generalized aggressive periodontitis showed lower IgG avidities to serotype c than those with chronic periodontitis, though no statistically significant difference was found. CONCLUSION: A. actinomycetemcomitans serotype c may play a significant role in chronic and generalized aggressive periodontitis, while A. actinomycetemcomitans serotype b may be associated with localized aggressive periodontitis in a Japanese population.

Actinobacillus Infections↗

The onset age of periodontal destruction.

In the present paper, the onset age of periodontal destruction is discussed. Results of epidemiological studies have shown that with increasing age, the prevalence of periodontitis in a population increases. Data show that after the age of 40 years, the % of the population affected by periodontitis remains rather constant. If it is supposed that the incidence of periodontitis after the age of 40 is zero (no new cases), then extractions resulting in edentulousness due to periodontitis should lead to a decrease of the prevalence of periodontitis. However, after the age of 40 years, the prevalence of periodontitis remains about the same, whereas edentulousness due to periodontitis increases. This suggests that even at a relatively old age, the onset of periodontitis may occur. On the other hand, periodontal destruction has also been found in the primary dentition. Especially on the basis of family studies and studies on localized juvenile periodontitis patients, it can be supposed that in a substantial part of the population, periodontal destruction starts early in life.

Adolescent↗

Aspects of adaptive host response in periodontitis.

OBJECTIVE: To review host response in periodontitis with respect to cellular composition of lesions, T cell receptor (TCR) gene expression, cytokine profiles of T-helper (Th) cells and autoimmune components. MATERIAL AND METHODS: The studies included were confined to human material (biopsies, gingival crevicular fluid, blood from subjects with periodontitis). RESULTS AND CONCLUSIONS: In periodontitis lesions, plasma cells are the most common cell type and represent about 50% of all cells, while B cells comprise about 18%. The proportion of B cells is larger than that of T cells and Th cells occur in larger numbers than T cytotoxic cells. Polymorphonuclear cells and macrophages are found in fractions of less than 5% of all cells. Lesions in aggressive and chronic forms of periodontitis exhibit similar cellular composition. Differences in disease severity, however, may reflect increases in plasma cell and B cell densities. B cells serve as important antigen-presenting cells in periodontitis. The periodontitis lesion expresses a unique TCR gene repertoire that is different from that in blood. The role of superantigens in periodontitis is unclear. There are few studies using comparative designs and unbiased quantitative methods regarding Th-1 and Th-2 cells in periodontitis. The relative dominance of B cells and plasma cells in periodontitis lesions cannot entirely be explained by enhanced Th-2 functions but maybe because of an imbalance between Th-1 and Th-2. Autoimmune reactions are evident in periodontitis lesions. The role of auto-antibodies in the regulation of host response in periodontitis, however, needs to be clarified. Auto-reactive B cells occur in larger proportions in subjects with periodontitis than in healthy controls.

Acute Disease↗

Validation of self-reported periodontal disease: a systematic review.

Self-report is an efficient and accepted means of assessing many population characteristics, risk factors, and diseases, but has rarely been used for periodontal disease (chronic periodontitis). The availability of valid self-reported measures of periodontal disease would facilitate epidemiologic studies on a much larger scale, allow for integration of new studies of periodontal disease within large ongoing studies, and facilitate lower-cost population surveillance of periodontitis. Several studies have been conducted to validate self-reported measures for periodontal disease, but results have been inconsistent. In this report, we conducted a systematic review of the validation studies. We reviewed the 16 studies that assessed the validity of self-reported periodontal and gingivitis measures against clinical gold standards. Seven of the studies included self-reported measures specific to gingivitis, four included measures only for periodontitis, and five included both gingivitis and periodontal measures. Three of the studies used a self-assessment method where they provided the patient with a detailed manual for performing a self-exam. The remaining 13 studies asked participants to self-report symptoms, presence of periodontal disease itself, or their recollection of a dental health professional diagnosing them or providing treatment for periodontal disease. The review indicates that some measures showed promise, but results varied across populations and self-reported measures. One example of a good measure is, "Has any dentist/hygienist told you that you have deep pockets?", which had a sensitivity of 55%, a specificity of 90%, positive predictive value of 77%, and negative predictive value of 75% against clinical pocket depth. Higher validity could be potentially obtained by the use of combinations of several self-reported questions and other predictors of periodontal disease.

Adolescent↗

Evidence-based care in orthodontics and periodontics: a review of the literature.

BACKGROUND: In this article, the author reviews the evidence-based literature in the fields of periodontics and orthodontics to clarify the relationship between orthodontic tooth movement and various types of common periodontal disorders. TYPES OF STUDIES REVIEWED: The first section is a review of the literature on common periodontal disorders. The second is a review of evidence-based studies in the combined fields of orthodontics and periodontics, with a focus on orthodontic treatment possibilities, limitations and risks inherent in patients with periodontal disorders, particularly active periodontal disease. RESULTS: The literature on orthodontic tooth movement as it relates to periodontal disease shows that proper orthodontic treatment in patients with excellent oral hygiene and the absence of significant periodontal disorders should not pose any significant periodontal risk. In the presence of poor oral hygiene, however, and under circumstances of certain types of periodontal disorders, fixed orthodontic appliances and tooth movement can contribute to significant deleterious periodontal consequences. CLINICAL IMPLICATIONS: This review provides a clear understanding of what is known about orthodontic treatment possibilities, limitations and inherent risks in patients who may have certain types of periodontal disorders. It also underscores the importance of teamwork among the restorative dentist, periodontist and orthodontist when planning treatment for these patients. The author also offers a specific patient management protocol for this interdisciplinary dental team to follow.

Clinical Protocols↗

Sensory innervation of the periodontal ligament in the incisor and molar of the monkey, Macaca fuscata. An immunohistochemical study for neurofilament protein and glia-specific S-100 protein.

Nervous elements in the periodontal ligament of the monkey, Macaca fuscata were investigated by means of immunohistochemistry for neurofilament protein (NFP) and S-100 protein. Thick nerve bundles with NFP-immunoreactivity entered the periodontal ligament through slits at the bottom of the alveolar socket, whereas thinner bundles, also NFP-immunoreactive, penetrated the ligament from the lateral wall of the alveolar socket. The NFP-immunopositive nerve fibers were densely distributed around the root apex in both incisors and molars. In the upper incisors, another dense distribution of NFP-positive nerves was found in the apical half of the lingual periodontal ligament and in the coronal half of the labial periodontal ligament. The periodontal nerve fibers in the incisors ramified in a dendritic fashion, terminating as free nerve endings within the periodontal ligament. Immunostaining for S-100 protein demonstrated the Schwann sheaths of nerves which showed the same distribution pattern as that of the NFP-immunopositive fibers in the periodontal ligament of the incisors. In molars, immunostaining for NFP and S-100 showed that nerves were numerous in the apical region of the periodontal ligament. However, NFP-immunopositive nerves were fewer than the S-100-positive nervous elements in the apical region in molars. This discrepancy suggests the presence of NFP-immunonegative nerves. Immunostaining for S-100 is thus useful for demonstration of neural elements in the periodontal ligament of molars. The S-100-immunoreactive neural elements in the periodontal ligament were more numerous in incisors than in molars. In addition to the free nerve endings, a small population of coiled nerve endings was observed in the periodontal ligament of molars. Most of the nerve fibers and cell bodies in the trigeminal ganglion showed NFP-immunoreactivity, whereas all in the mesencephalic nucleus of the trigeminal nerve were negative in NFP-reaction. This finding suggests that the periodontal ligament of molars receives a dual innervation from the trigeminal ganglion and mesencephalic nucleus.

Animals↗

Periodontal host modulation with antiproteinase, anti-inflammatory, and bone-sparing agents. A systematic review.

BACKGROUND: The use of modulating agents, including inhibition of matrix metalloproteinases (MMPs) with antiproteinases, blocking production of proinflammatory cytokines and prostaglandins with anti-inflammatory drugs, and inhibiting activation of osteoclasts with bone-sparing agents, has been postulated to be of therapeutic value as an adjunctive therapy to the management of chronic periodontitis. RATIONALE: The objective of this systematic review of the literature was to assess the adjunctive efficacy of antiproteinase, anti-inflammatory, and bone-sparing host-modulating agents in the treatment of gingivitis, aggressive periodontitis, and chronic periodontitis. FOCUSED QUESTIONS: 1. In patients with periodontal diseases, what is the effect of host-modulation agents, alone or combined with conventional therapy, compared to conventional therapy alone as assessed by clinical, radiographic, adverse, and patient-centered outcomes? 2. In patients with dental implants, what is the effect of host-modulation agents on implant success assessed by clinical, radiographic, adverse, and patient-centered outcomes? SEARCH PROTOCOL: MEDLINE, Embase, and the Cochrane Library databases were searched without language restrictions through April 1, 2002 for studies that used tetracycline (TET)-related matrix metalloproteinase (MMP) inhibitors, or non-steroidal anti-inflammatory drugs (NSAIDs) and bisphosphonate anti-osteolytic agents. The investigation also included hand searching of journals and contacting authors and industry experts. SELECTION CRITERIA INCLUSION CRITERIA: Only human studies (randomized controlled clinical trials, cohort studies, case-control studies, cross-sectional studies, and case series) were selected. Studies were on subjects with gingivitis, aggressive or chronic periodontitis, or dental implants. Interventions included TET-related MMP inhibitors, NSAIDs, or bisphosphonate anti-osteolytic agents. EXCLUSION CRITERIA: Studies that used MMP tissue inhibitors as diagnostic or prognostic indicators of periodontal disease or that evaluated short-term systemic antibodies or locally delivered levels of drugs with antiproteinase activity were excluded. DATA COLLECTION AND ANALYSIS: The primary outcomes for assessment were changes in bone or clinical attachment levels (CAL); secondary outcomes included clinical measures of plaque, gingival inflammation, probing depth (PD), and mobility. Summary data appropriate for meta-analysis were pooled using a weighted average and analyzed using a standardized difference; the results were checked with both fixed-effects and random-effects models. MAIN RESULTS: 1. A meta-analysis done on the studies reporting changes in CAL and PD following administration of sub-antimicrobial doses of doxycycline (SDD) in conjunction with scaling and root planing (SRP) in patients with periodontitis showed a statistically significant beneficial adjunctive effect. 2. There were insufficient data to provide meta-analyses on periodontal patients treated with other host-modulating agents; descriptive tables are included. 3. NSAIDS show promise in their ability to slow periodontal disease. 4. Preliminary data on bisphosphonate agents indicate there is a potential role for these agents in periodontitis management. 5. There are a very limited number of studies on host-modulating agents and dental implants and no analyses were possible. 6. Because the treatment methodologies and clinical variables differed considerably among the studies, it is difficult to summarize the information and identify a reliable total patient population. REVIEWERS' CONCLUSIONS: 1. Large multi-center trials are needed to evaluate the role of host-modulating agents in the treatment of periodontitis. 2. NSAIDS and bisphosphonate drugs may have a potential adjunctive role in periodontal therapy. 3. The adjunctive use of SDD with SRP is statistically more effective than SRP alone in reducing PD and in achieving CAL gain.

Anti-Inflammatory Agents, Non-Steroidal↗

Non-human primates used in studies of periodontal disease pathogenesis: a review of the literature.

The inability to examine initiation and progression of periodontal disease and to assess certain therapies in humans has led to a great interest in the use of animal models in periodontal research. Some of the most prominent animals used are non-human primates. This article reviews the characteristics of non-human primate models in periodontal health, in the transition from health to gingivitis to periodontitis, and in experimental gingivitis and periodontitis. Where possible, the results of these studies are compared with results from human studies. Only a few studies have compared in detail the anatomy, physiology, immunology, and tissue interactions in monkeys with those of humans. With the exceptions of differences and variations in size of the dentition, the number of each tooth type as well as larger canines, presence of diastemata between anterior teeth, and an edge-to-edge relationship of the incisors, the dental and periodontal anatomy of non-human primates seem quite similar to that of humans. Clinically healthy gingiva can be established and maintained in non-human primates, and gingivitis as well as periodontitis occur in these animals. It is possible to induce experimental periodontitis by placement of peri-dental silk ligatures or orthodontic elastics as well as by surgical removal of alveolar bone. Although the most appropriate model for studies of periodontal disease pathogenesis in non-human primates appears to involve the application of silk ligatures, some difficulties may occur in establishing periodontal break-down by using this model. Many clinical, histological, microbiological, and immunological characteristics of spontaneous and experimental marginal inflammation in most non-human primates are similar to those in humans. The most significant differences between small non-human primates and humans are the very limited number of lymphocytes and plasma cells in the inflammatory infiltrate of squirrel monkeys (Saimiri sciureus) and marmosets. Therefore, the use of squirrel monkeys and marmosets may not be appropriate in many studies of periodontal disease pathogenesis. The most significant microbial differences between macaque species and humans are a lower proportion of Actinomyces species, the presence of a catalase-producing Prevotella melaninogenica strain, and the high carrier rate for Actinobacillus actinomycetemcomitans in subgingival plaque of macaque species. The significance of these differences is presently unknown. It is concluded that the use of many non-human primate species due to the apparent close anatomic and biologic similarities to humans is appropriate in experimental studies of periodontal disease, provided the use of laboratory animals is requisite and lower species are not applicable.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗