Bovine Bone Promotes Osseous Protection via Osteoclast Activation.

The current study aimed at investigating the long-term biological mechanisms governing bone regeneration in osseous defects filled with bovine bone (BB). Tooth extraction sockets were filled with BB or left unfilled for natural healing in a C57BL/6 mouse alveolar regeneration bone model (n = 12). Seven weeks later, the alveolar bone samples were analyzed histologically with hematoxylin/eosin and tartrate-resistant acid phosphatase staining. A separate group (n = 10) was used for RNA sequencing. Osteoclast inhibition was induced by zoledronic acid (ZA) administration at 2 wk postextraction in a third group (n = 28) for examination of osseous changes and cellular functions with micro-computed tomography and quantitative reverse transcription polymerase chain reaction, respectively. Histological and radiological osseous healing was observed in both BB-filled and normal-healing sockets. However, BB regenerated bone showed significant robust expression of genes associated with bone homeostasis and osteoclasts' function. Osteoclasts' inhibition in BB-filled sockets led to decreased bone resorption markers and reduced bone formation to a greater extent than that observed in osteoclasts' inhibition with natural healing. BB displays long-term biologically active properties, despite a naive osseous histological appearance. These include activation of osteoclasts, which in turn promotes osseous remodeling and maturation of ossified bone.

[Ridge preservation after tooth extraction: what do we know today].

Following tooth removal, varying amounts of bone resorption take place due to qualitative and quantitative changes that occur at the alveolar bone around the extraction site. Alveolar bone is a tooth dependent structure and therefore, after a tooth is extracted, dimensional bone reduction takes place both, horizontally and vertically resulting in changes that may lead to esthetic and functional problems. Such deformities of the alveolar ridge may compromise future implant placement as well as esthetic results when a fixed partial denture is constructed in a visible area. In order to preserve ridge dimensions following tooth extraction, particularly where future implant placement is planned, ridge/socket preservation is recommended. Ridge/socket preservation is any procedure undertaken at the time of or following an extraction that is designed to minimize external resorption of the ridge and maximize bone formation within the socket. In certain situations it not advisable to perform ridge preservation at the time of tooth extraction thus, preservation is delayed by few weeks (6-8). This paper reviews the various socket/ridge preservation techniques and the diverse materials used to fill those deficient tissues or prevent their collapse. Scientific literature review is discussed.

Assessing the levels of immunoglobulins in the saliva of diabetic individuals with periodontitis using checkerboard immunodetection.

BACKGROUND: Current methods for determining salivary antibodies are cumbersome for large-scale screenings. OBJECTIVES: To test checkerboard immunodetection for monitoring salivary antibodies and to profile them in diabetic individuals with periodontitis. METHODS: Salivary anti-Porphyromonas gingivalis, anti-Actinobacillus actinomycetemcomitans and total IgA levels of 10 individuals were compared using checkerboard immunoblotting and enzyme-linked immunosorbent assay (ELISA). RESULTS: Close correlation between both methods was found in anti-P. gingivalis IgA and total IgA, but not in anti-A. actinomycetemcomitans IgA, because of high background levels in ELISA. Thereafter, checkerboard immunodetection was used to compare salivary antibodies of 20 adult type II diabetic with 32 non-diabetic individuals with (n=22) or without (n=10) periodontitis. Patients with periodontitis (regardless of their diabetic condition) expressed increased levels of total IgA in both whole and parotid saliva, but reduced levels of anti-A. actinomycetemcomitans IgA in whole saliva. Consequently, the proportion of anti-A. actinomycetemcomitans IgA in the total IgA was lower in saliva of patients with periodontitis compared with healthy controls. CONCLUSIONS: Checkerboard immunodetection was reliable and economical for screening saliva samples for multiple antibody reactions. Our results support previous reports which suggested that patients with periodontitis are able to secrete high levels of salivary Ig, but are hampered in targeting their salivary response toward A. actinomycetemcomitans.

Age-dependent deficiency in saliva and salivary antibodies secretion in Down's syndrome.

OBJECTIVE: Down's syndrome (DS) individuals suffer from an increased susceptibility to infections. Here, we assessed age-related changes in the salivary-specific humoral immunity of DS subjects. DESIGN: Parotid and whole saliva were collected from a young group of DS (YDS, n=30, 23.3+/-4 years), an older group of DS individuals (ODS, n=10, 51.9+/-8 years) and compared to two age-matched groups of healthy volunteers--a young group (YC, n=29, 22.8+/-5 years) and an older group (OC, n=10, 48.4+/-9 years). The levels of total IgA, and specific antibodies to three common oral pathogens (Porphyromonas gingivalis, Actinobacillus (Aggregatibacter) actinomycetemcomitans and Streptococcus mutans) were analysed. RESULTS: The limited increases in IgA concentrations could not compensate the dramatic reduction in the salivary flow rate observed in DS individuals. Therefore, the median secretion rates of the specific antibodies in whole and parotid saliva were 70-77% and 34-60% (respectively) lower in YDS individuals as compared to YC and farther 77-100% and 75-88% (respectively) lower in ODS compared to YDS. In contrast, the antibody secretion rates were similar for parotid saliva, or even increased for whole saliva of OC, compared with YC. Consequently, a dramatic cumulative extreme reduction (>92%) in the bacterial specific salivary antibodies differentiated the adult DS individuals from to their age-matched controls. CONCLUSIONS: Our results indicate a severe immunodeficiency in the secretion rate of the specific salivary IgA response of in DS individuals which intensifies with age.

Salivary LL-37 secretion in individuals with Down syndrome is normal.

Antimicrobial peptides play an important role in the innate immune response. Deficiency in salivary LL-37 antimicrobial peptide has been implicated in periodontitis in patients with morbus Kostman syndrome. Down syndrome is associated with periodontitis, diminished salivary flow, and salivary immunoglobulin deficiency. In the present study, levels of LL-37 and its hCAP18 precursor were measured in saliva samples from young individuals with Down syndrome and compared with levels in those from age-matched healthy controls. LL-37 and human cathelicidin antimicrobial protein (hCAP18) were detected in whole but not in parotid saliva. hCAP18 was more abundant than LL-37. The concentrations of salivary hCAP18 and LL-37 were found to be higher in individuals with Down syndrome than in healthy controls, but their secretion rates were similar. We concluded that, while the adaptive immunity of individuals with Down syndrome is impaired at the oral mucosa, the secretion rate of the LL-37 component of the innate immune system is normal.

The outcome of a preventive dental care programme on the prevalence of localized aggressive periodontitis in Down's syndrome individuals.

BACKGROUND: Periodontal disease in Down's syndrome (DS) individuals develops earlier and is more rapid and extensive than in age-matched normal individuals. The present study evaluated a group of DS patients, who had been participating in a 10-year preventive dental programme, for the impact of the programme on their periodontal status. METHODS: Thirty DS patients (mean age 23.3 +/- 4 years) were compared with 28 age-matched healthy controls (mean age 22.8 +/- 5 years). The hygiene level, gingival condition and periodontal status (periodontal probing depth, clinical attachment level and radiographic alveolar bone loss) were determined. RESULTS: In spite of similar oral hygiene and gingival measures, DS patients, as opposed to the control ones, had a severe periodontal disease. The prevalence, extent and severity of periodontitis in the DS group were significantly greater than in the control group. The teeth most commonly and severely affected were the lower central incisors and the upper first molars. DS patients lost significantly more teeth due to periodontitis. CONCLUSIONS: The clinical and radiographic picture found in the present DS group is characteristic of localized aggressive periodontitis. Within the limitations of this study, it seems that the preventive dental programme had no effect on periodontal destruction progression of localized aggressive periodontitis in DS individuals and that impaired oral hygiene plays a relatively minor role in the pathogenesis of this disease. Future controlled studies are needed to assess the effectiveness of different preventive dental programmes in preventing the progression of periodontitis in DS patients.

Acid-etched and erbium:yttrium aluminium garnet laser-treated enamel for fissure sealants: a comparison of microleakage.

OBJECTIVES: A pilot study aimed to compare the microleakage of pit and fissure sealants in acid-etched and Erbium:Yttrium Aluminium Garnet (Er:YAG)-treated enamel. METHODS: Forty permanent noncarious young molars and premolars, which were extracted for orthodontic reasons, were selected. The teeth were divided into four groups, with five molars and five premolars in each group. The groups were treated as follows: (1) group A--laser irradiation of the enamel of the occlusal surface without contact and in scanning mode was carried out using an Er:YAG laser, placement of sealant material, light curing, and thermocycling between 6 degrees and 55 degrees C; (2) group B--the same as group A, but with no thermocycling; (3) group C--acid etching of the enamel surface, placement of sealant material, light curing and thermocycling; and (4) group D--the same as group C, but with no thermocycling. After being immersed in 1% methylene blue solution, all teeth were sectioned in the mesio-distal dimension into four slices. Images of the slices were then scanned to a Macintosh G3 computer and examined for marginal leakage. Leakage was measured by the degree of dye penetration. Three independent examiners evaluated the dye penetration. RESULTS: No penetration of dye material was observed in any of the slices in any of the four groups by any of the examiners. CONCLUSIONS: No difference in microleakage was seen between lasing or acid etching, and therefore, the results of the present study would suggest that the technique may be efficacious.

Comparative study of dentine permeability after apicectomy and surface treatment with 9.6 microm TEA CO2 and Er:YAG laser irradiation.

Failure of apicectomies is generally attributed to dentine surface permeability as well as to the lack of an adequate marginal sealing of the retrofilling material, which allows the percolation of microorganisms and their products from the root canal system to the periodontal region, thus compromising periapical healing. The purpose of this study was to evaluate dentine and the marginal permeability after apicectomy and surface treatment with 9.6 micro m TEA CO(2) or Er:YAG 2.94 micro m laser irradiation. Sixty-five single rooted human endodontically treated teeth were divided into five experimental groups: group I (control), apicectomy with high speed bur; group II, similar procedure to that of group I, followed by dentinal surface treatment with 9.6 micro m CO(2) laser; group III, similar procedure to group I followed by dentinal surface treatment with Er:YAG laser 2.94 micro m; group IV, apicectomy and surface treatment with CO(2) 9.6 micro m laser; and group V, apicectomy and surface treatment with Er:YAG laser 2.94 micro m. The analysis of methylene blue dye infiltration through the dentinal surface and the retrofilling material demonstrated that the samples from the groups that were irradiated with the lasers showed significantly lower infiltration indexes than the ones from the control group. These results were compatible with the structural morphological changes evidenced through SEM analysis. Samples from groups II and IV (9.6 micro m CO(2)) showed clean smooth surfaces, fusion, and recrystallized dentine distributed homogeneously throughout the irradiated area sealing the dentinal tubules. Samples from groups III and V (Er:YAG 2.94 micro m) also presented clean surfaces, without smear layer, but roughly compatible to the ablationed dentine and without evidence of dentinal tubules. Through the conditions of this study, the Er:YAG 2.94 micro m and the 9.6 micro m CO(2) laser used for root canal resection and dentine surface treatment showed a reduction of permeability to methylene blue dye.

[Lasers in dentistry. Part A--Development, characteristics, structure, principles of operation and types of lasers].

Laser technology is developing very quickly. New Lasers with a wide range of characteristics are available today and are being used in the various fields of dentistry. The search for new devices and technologies for dental procedures was always challenging and in the last two decades much experience and knowledge has been gained. The purpose of this series of articles published in the journal of the Israel Dental Association in three parts is to present the Israeli dentist a comprehensive and contemporary overview which will assist him in understanding the potential of the use of laser technology for clinical applications in dentistry. The first part will describe the history and development of lasers in dentistry, the characteristics and structure of lasers as well as their principles of operation. A description of the different types of lasers used today in dentistry will be presented in the first part. The second part will describe the interaction of lasers with biological tissues and their effect on the soft and hard tissues of the oral cavity as well as on the dental pulp. Laser safety in the dental practice will also be discussed. The third part will focus on clinical applications of Lasers in Dentistry: pits and fissures sealing, dentin desensitization, cavity preparations, composite curing, surgical procedures and tooth whitening. Current status of using lasers in periodontics, endodontics and dental implantology will be discussed and possible future clinical applications of lasers in dentistry will be presented.

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.

[Lasers in dentistry. Part B--Interaction with biological tissues and the effect on the soft tissues of the oral cavity, the hard tissues of the tooth and the dental pulp].

The interaction of laser energy with target tissue is mainly determined by two non operator-dependent factors: the specific wavelength of the laser and the optical properties of the target tissues. Power density, energy density, pulse repetition rate, pulse duration and the mode of energy transferring to the tissue are dictated by the clinician. Combination of these factors enables to control optimal response for the clinical application. Four responses are described when the laser beam hits the target tissue: reflection, absorption, transmission and scattering. Three main mechanisms of interaction between the laser and the biological tissues exist: photothermic, photoacoustic and photochemical. The effect of lasers on the soft tissues of the oral cavity is based on transformation of light energy into thermal energy which, in turn heats the target tissue to produce the desirable effect. In comparison to the scalpel used in surgical procedures, the laser beam is characterized by tissue natural sterility and by minimum bleeding during the surgical procedures due to blood vessels welding. The various effects achieved by the temperature elevation during the laser application on the soft tissue are: I. coagulation and hemostasis II. tissue sterilization III. tissue welding IV. incision and excision V. ablation and vaporization Ablation and melting are the two basic modalities by which the effect of lasers on the hard tissues of the tooth is produced. When discussing the effect of laser on dental hard tissues, the energy absorption in the hydroxyapatite plays a major role in addition to its absorption in water. When laser energy is absorbed in the water of the hard tissues, a rapid volume expansion of the evaporating water occurs as a result of a substantial temperature elevation in the interaction site. Microexplosions are produced causing hard tissue disintegration. If pulp temperatures are raised beyond 5 degrees C level, damage to the dental pulp is irreversible. Histologically, after laser ablation, presence of odontoblastic nuclei is important. Consistency and composition of the intracellular tissue is another factor influencing cell viability. If heat is intensive and exists for an extended time, the consistency of the intracellular ground substance may not be preserved. Accordingly, the application of excessive energy densities has been shown to result in significant damage to pulp tissue and in particular to odontoblasts. Studies showed that the use of Er:YAG laser to treat dental hard tissues is both safe and effective for caries removal, cavity preparation and enamel etching.

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.

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.

Dental anxiety among patients prior to different dental treatments.

The purpose of the present study was to evaluate dental anxiety among patients anticipating various dental treatments. One hundred and eighty patients who were scheduled for specific dental treatments at the School of Dental Medicine, the Hebrew University--Hadassah, Jerusalem, Israel participated in the study. Patients were anticipating one of the following dental procedures: scaling, filling, root canal therapy, preparation for crown, periodontal surgery or extraction. For each of the six dental treatments, 30 patients were selected at random. Dental Anxiety Scale (DAS) questionnaires were completed by the patients while waiting for their treatments. The results indicated that extraction caused the highest score, followed by scaling (though not significantly). Patients in the 35 to 49 year age group showed the highest total DAS scores. Women demonstrated higher total DAS scores than men. The relative influence of gender, type of treatment and age on the anxiety scores is demonstrated by using logistic regression, which revealed gender to have the strongest impact on the DAS scores, followed by the type of treatment and age.

The description of a unique population with a very high prevalence of localized juvenile periodontitis.

The reported prevalence of localized juvenile periodontitis (LJP) amongst teenagers and young adults varies greatly. The etiology of LJP has been related to Actinobacillus actinomycetemcomitans (Aa), and it has also been suggested that there may be a transmission of Aa within families resulting in the familial distribution of the disease. This study describes the high prevalence of LJP in adolescents, 12-20 years of age, from a group of nuclear families living and functioning in a closed, closely knit community. The survey was carried out on a population of teenagers that had attended the same school and their siblings. All students attending that school and their siblings were examined. They were given a periodontal examination and a questionnaire relating to their demographic details and their personal oral hygiene habits. The periodontal examination was limited to the incisors and first molar teeth. Plaque index (PlI), gingival index (GI), the presence or absence of bleeding on probing (BOP), probing pocket depth (PPD) and recession were measured. All patients having at least two of the examined sites with probing pocket depth > or =5 mm or one site > or =6 mm were considered as possible sufferers from LJP and had a full mouth periapical radiographic survey carried out using a paralleling technique to confirm the diagnosis. At the sites with probing pocket depth > or =5 mm, a Shei ruler was used to measure the % of the root coronal to the alveolar bone. A cut off point of > or =20% was used as a measure of true bone loss confirming the clinical diagnosis of LJP. 86 individuals from 30 families comprised the population of interest. There were 44 males and 42 females with a mean age of 14.7+/-2.3. Of the 86 individuals examined, 33 individuals from 15 families were diagnosed as having LJP (38.4%). None of the individuals examined showed any evidence of the generalized form of juvenile periodontitis. The mean age of the LJP patients was 15+/-2.3 yrs. with a 1:1.75 male to female ratio. Except for 2 pairs of families with genetic ties, no familial connections could be traced between the different nuclear families affected by LJP despite repeated and intensive questioning. There were no significant differences in the PlI and the GI between the groups while the LJP group had significantly higher BOP, PPD and PAL than the non-LJP group. These finding strongly suggest an environmental influence in the etiology of the disease.

Periodontal health and the role of the dental hygienist.

This study was conducted to evaluate the influence of hygienist services in an Israeli kibbutz (communal settlement) upon periodontal disease levels and periodontal treatment needs. The Periodontal Index (PI) and the Community Periodontal Index of Treatment Needs (CPITN) were utilised to examine 412 subjects of which 202 adult participants resided in a kibbutz employing a hygienist and 210 participants resided in one of three kibbutzim lacking a history of hygienist employment. Examinations were conducted by two calibrated examiners. Results revealed a gradual increase in the CPITN and PI scores with age and generally statistically significantly higher periodontal pathology and treatment need scores among the population not employing a dental hygienist (especially within the 35-44 age grouping). The results of this study suggest that employment of a dental hygienist may be an effective approach to lower the burden of periodontal disease within a community.

Clinical and antimicrobial effects of a single episode of subgingival irrigation with tetracycline HCl or chlorhexidine in deep periodontal pockets.

15 adults, each providing 4 non-adjacent untreated periodontal pockets with a probing depth (PD) exceeding 6 mm, volunteered for a randomized, split-mouth, double-blind, clinical study evaluating subgingival irrigation with chlorhexidine (CHX) or tetracycline HCl (TTC). The study protocol included oral hygiene instructions followed by scaling and root planing. Experimental and immediately adjacent teeth did not receive instrumentation. The 4 deep periodontal pockets in each patient were assigned to be irrigated with 150 ml CHX (0.12%), TTC (10 or 50 mg/ml; TTC10, TTC50), or sterile saline (control) in a single episode. Post-irrigation mechanical plaque control was supported by 2x daily CHX rinses throughout the 12-week observation interval. Recordings of oral hygiene (P1I), gingival health (GI), bleeding on probing (BoP), probing depth (PD), clinical attachment level (CAL), and microbial morphotypes from subgingival paper point samples were performed pre-irrigation, and at 1, 2, 4, 6, 8, 10, and 12 weeks post-irrigation. Mean post-irrigation P1I was low, fluctuating between 0.0 and 0.4, without significant differences between experimental groups. Mean pre-irrigation GI approximated 1.4 and reached 0.8 at the exit of study without significant differences between experimental groups. All experimental sites exhibited BoP pre-irrigation. BoP was significantly reduced in TTC50 compared to TTC10, CHX and control sites from week 8 post-irrigation. PDs were reduced for the experimental groups with TTC50 exhibiting the strongest reduction. CALs remained unaltered from pre-irrigation for TTC10, CHX and control sites over the 12-week observation interval, whereas TTC50 sites consistently improved to significantly differ from all other groups at week 10 and 12 post-irrigation. The distribution of bacterial morphotypes was significantly altered towards one of periodontal health for all experimental groups with a profound effect for TTC50 sites. Our results suggest that subgingival irrigation with TTC solutions at high concentrations may have a role in the management of adult periodontitis.

The nature and extent of jaw involvement in Gaucher disease: observations in a series of 28 patients.

A wide variety of osteoarticular pathoses plague the clinical course of many patients with Gaucher disease. Osseous lesions involving the jaws have been described, usually as isolated case reports. The purpose of this study was to ascertain the nature and extent of mandibulo-maxillofacial pathosis in 28 patients with documented Gaucher disease by means of panoramic radiography. Twenty-five of the 28 patients displayed radiographic evidence of jaw involvement. The most prevalent finding was gross widening of marrow spaces; frank radiolucencies, endosteal scalloping, cortical thinning, root resorption, and inferior displacement of the mandibular canal or effacement of its cortices were also seen. A previously unreported finding was delayed eruption of permanent teeth, which was seen in more than one half of the patients who were under 20 years of age. Osseous changes throughout the jaws may be more common than previously suspected and may alert the dentist to the presence of the disease.

Effects of tetracyclines on the pathologic activity of endotoxin: in vitro and in vivo studies.

Lipopolysaccharide (LPS) is considered to be one of the major virulence factors of Gram-negative bacteria. Recently, tetracyclines (TTCs) were found to prevent the patho-physiological changes associated with LPS in vivo and the secretion of inflammatory mediators in vitro. However, the mechanism by which TTCs prevents LPS-induced pathology in vivo is still unclear. In order to shed light on that problem, we carried out in vitro and in vivo experiments. TTC inhibited the secretion of nitric oxide (NO) and TNF alpha from LPS-stimulated macrophages and inhibited macrophage-induced thymocyte proliferation. However, TTC inhibited NO secretion with use of concentrations five-fold lower than those that inhibited TNF alpha secretion and thymocyte proliferation. The secretion of NO was inhibited by the addition of TTC to the cultures up to 6 hrs post-LPS stimulation. TTC inhibition of LPS-induced NO secretion was not reversed by the addition of recombinant TNF alpha, and TTC inhibition of LPS-induced TNF alpha secretion was not reversed by the addition of NO donor. These results suggest that the inhibition of TNF alpha by TTC is not the result of the inhibition of LPS-induced NO secretion or vice versa. In vivo experiments had shown that TTC prevented mortality in LPS-treated mice, but not in mice pre-sensitized with galactosamine prior to the LPS challenge. These results suggest that TTC activity in vivo is due not to the suppression of synthesis of inflammatory mediators but rather to the induction of acute phase-like response, which antagonizes the LPS-induced activity.