Biomedical subjects

W A Soskolne

Publications and source records attributed to W A Soskolne.

At least 19 recordsLinked to original sources

PubMed2002

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↗

PubMed2001

The relationship between periodontal diseases and diabetes: an overview.

Diabetes mellitus, caused by the malfunction of insulin-dependent glucose and lipid metabolism, presents with the classical triad of symptoms: polydypsia, polyuria, and polyphagia which are often accompanied by chronic fatigue and loss of weight. Complications of diabetes mellitus include retinopathy, nephropathy, neuropathy, and cardiovascular disease. Periodontal diseases are infections affecting the periodontium and resulting in the loss of tooth support. The association between diabetes mellitus and periodontitis has long been discussed with conflicting conclusions. Both of these diseases have a relatively high incidence in the general population (diabetes 1% to 6% and periodontitis 14%) as well as a number of common pathways in their pathogenesis (both diseases are polygenic disorders with some degree of immunoregulatory dysfunction). On the one hand, numerous reports indicate a higher incidence of periodontitis in diabetics compared to healthy controls, while other reports fail to show such a relationship. Clarification of this dilemma is occurring as the diagnostic criteria for periodontitis and diabetes mellitus improve, controlled studies with increased sample sizes are carried out, and the studies take into account major confounding variables that impact on the pathogenesis of both diseases. Current studies tend to support a higher incidence and severity of periodontitis in patients with diabetes mellitus. The overview looks at the bidirectional relationship between periodontitis and diabetes. An analysis of the National Health and Nutrition Examination Survey (NHANES) III data set confirms the previously reported significantly higher prevalence of periodontitis in diabetics than in non-diabetics (17.3% versus 9%). The analysis of the data also shows that the prevalence of diabetes in patients with periodontitis is double that seen in the non-periodontitis patients (12.5% versus 6.3%) and that this difference is also statistically significant. The pathogenesis of the 2 diseases is reviewed with an emphasis on common genetic and immune mechanisms. On the basis of the overview, 2 hypotheses for testing the relationship between periodontitis and diabetes are discussed. The first proposes a direct causal or modifying relationship in which the hyperglycemia and hyperlipidemia of diabetes result in metabolic alterations that may then exacerbate bacteria-induced inflammatory periodontitis. The second hypothesis proposes that a fortuitous combination of genes (gene sets) could result in a host who, under the influence of a variety of environmental stressors, could develop either periodontitis or diabetes or both.

Diabetes Complications↗

PubMed2000

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↗

PubMed2000

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↗

PubMed1998

Delayed immediate implants: alveolar bone changes during the healing period.

Delaying the placement of immediate fixtures by 6-8 weeks after extraction of the natural dentition allows for the elimination of associated infective processes, the achievement of maximum osteoblastic activity that theoretically could help the osseointegration process and complete wound covering that simplifies the placement of grafts or membranes. This study examines the healing associated with 21 fixtures in 14 patients. The fixtures were placed into sockets 6-8 weeks after tooth extraction without the use of barrier membranes or bone substitutes. Measurements were taken immediately prior to fixture placement and 3-6 months later at the abutment placement. Alveolar bone height, the remaining socket depth and diameter and the depth to which a 3.75 mm fixture could be inserted into the socket were measured. After fixture placement the vertical and horizontal measurements from the cover screw to the surrounding alveolar bone and the distance from the cover screw to the CEJ of the adjacent tooth were recorded. All fixtures were integrated at exposure with 1 failure during the follow-up period. The distance from the cover screw to the buccal plate decreased by a mean of 2.17 mm. There was an increase in the mean vertical bone height at all 4 surfaces. When horizontal defects were present, the mean vertical distance decreased from 2.5 +/- 0.37 mm to 0.36 +/- 0.64 mm. When horizontal defects were absent, the mean vertical distance decreased from 3.86 +/- 0.58 mm to 0.48 +/- 0.25 mm. There was also a marked decrease in the horizontal distance between the bone margin and the surface of the fixture from 1.6 +/- 1.73 mm to 0.02 +/- 0.02 mm. These results indicate a strong tendency for the defects to fill-in the horizontal plane and for bone growth to occur in the vertical plane to the height of the cover screw. In conclusion the delayed immediate placement of fixtures has a good short-term prognosis with bone regeneration occurring around the defect without the use of barrier membranes or bone substitutes.

Adolescent↗

PubMed1998

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.

Adolescent↗

PubMed1998

An in vivo study of the chlorhexidine release profile of the PerioChip in the gingival crevicular fluid, plasma and urine.

The release profile of chlorhexidine from the PerioChip (Chip), a biodegradable local delivery system that contains 2.5 mg of chlorhexidine gluconate (CHX) in a cross-linked hydrolyzed gelatin matrix, into the gingival crevice, was evaluated in an in vivo, open label, single-center, 10-day pharmacokinetic study conducted on 19 volunteers with chronic adult periodontitis. Each volunteer had a single chip inserted into each of 4 selected pockets, with probing pocket depths of between 5-8 mm, at time 0. Gingival crevicular fluid (GCF) samples were collected using filter paper strips prior to Chip placement and at 2 h, 4 h, 24 h and 2, 3, 4, 5, 6, 8, and 9 days post-Chip placement. The GCF volume was measured using a calibrated Periotron 6000. Blood samples were collected at times 0, 1, 4, 8, 12 h and 5 days post-dosing. Urine was collected as a total 24-h specimen immediately post-dosing and 2 single samples at time 0, prior to dosing, and 5 days. The CHX was eluted from the paper strips and the CHX levels in GCF, blood and urine quantified using HPLC. The results indicate an initial peak concentration of CHX in the GCF at 2 h post-Chip insertion (2007 microg/ml) with slightly lower concentrations of between 1300-1900 microg/ml being maintained over the next 96 h. The CHX concentration then progressively decreased until study conclusion with significant CHX concentrations (mean=57 microg/ml) still being detectable at study termination. CHX was not detectable in any of the plasma or urine samples at any time point during the study. These results indicate that the PerioChip can maintain clinically effective levels of CHX in the GCF of periodontal pockets for over 1 week with no detectable systemic absorption.

Adult↗

PubMed1998

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.

Acute-Phase Reaction↗

PubMed1998

Epidemiological and clinical aspects of periodontal diseases in diabetics.

The association between diabetes mellitus and periodontal disease has long been discussed, with conflicting conclusions. On the one hand, numerous reports indicate a high prevalence of periodontal disease in diabetics compared to healthy controls, while others fail to show such a relationship. Clarification of this dilemma has been occurring as the diagnostic criteria for periodontal disease destruction improve and the number and size of the populations surveyed grow. This review is based on a selective review of the literature from the present decade. To date, based mainly on an extensive study of the Pima Indians who have an extremely high incidence of non-insulin-dependent diabetes mellitus (NIDDM), it seems to be clear that patients with NIDDM have a higher prevalence and severity of periodontal disease destruction than non-diabetics in the same population. However, it must be borne in mind that these data are for a special population. Studies on patients with insulin-dependent diabetes mellitus (IDDM) indicate results similar to those found in studies on NIDDM. There is an increase in prevalence and severity of periodontitis compared to controls. For both IDDM and NIDDM, there does not appear to be any correlation between the prevalence or the severity of periodontal disease and the duration of diabetes. Well-controlled diabetic patients as measured by blood glycated hemoglobin levels have less severe periodontal disease than poorly controlled diabetics. The principles of treatment of periodontitis in diabetics are the same as those for non-diabetic patients and are consistent with our approach to all high-risk patients who have already developed periodontal disease. The major efforts should be directed at the prevention of periodontitis in patients at risk of developing diabetes. Another important clinical question relates to the influence of periodontal disease on the control of the diabetic state. Here again the literature is unclear; however, a recent development suggests that effective control of periodontal infection in patients with diabetes reduces the level of advanced glycosylation end products in the serum. If future studies can confirm this effect, then periodontal infection control must be considered an integral part of diabetic control.

Diabetes Complications↗

PubMed1997

Bacterial lipopolysaccharide induces early and late activation of protein kinase C in inflammatory macrophages by selective activation of PKC-epsilon.

Experiments from our and other laboratories have shown that specific inhibitors of protein kinase C (PKC) inhibited the secretion of nitric oxide, TNF alpha, and IL-1 beta from lipopolysaccharide (LPS)-stimulated macrophages, suggesting an important role for PKC in the inflammatory response. The present study was designed to investigate the mechanism whereby LPS stimulates PKC activity in inflammatory macrophages. Mouse macrophages were stimulated with 0-1 microgram/ml LPS for 0-18 hours, and PKC activity was detected in cell lysates. PKC isoform specificity was determined by blocking PKC activity with isoform-specific antibodies. Treatment of macrophages with 1 microgram/ml LPS induced a two-fold increase in PKC activity within 15 minutes and an additional more significant peak of PKC activity appeared 3 hours post-LPS stimulation. A lower dose of LPS (10 ng/ml) induced the later peak only. The enhancement in PKC activity induced by LPS occurred in both the cytosol and membrane fractions, but the enhancement in the membrane fraction was significantly greater than in the cytosol. The increase in PKC activity in both peaks was abolished only by the addition of anti-PKC-epsilon antibody. The present experiments suggest that PKC activation is an important pathway in the LPS-induced secretory response of macrophages and that PKC-epsilon is the major isoform involved.

Animals↗

PubMed1997

The effects of 17 beta-estradiol on chondrocyte differentiation are modulated by vitamin D3 metabolites.

Both 17 beta-estradiol (17 beta) and the vitamin D metabolites, 1,25-(OH)2D3(1,25) and 24,25-(OH)2D3(24,25), regulate endochondral bone formation in vivo and in vitro. The effects of 17 beta are sex-specific and cell maturation-dependent. Similarly, the effects of 1,25 and 24,25 are cell maturation-dependent, with 1,25 affecting growth zone chondrocytes (GC) and 24,25 affecting resting zone chondrocytes (RC). This study examined whether the response of chondrocytes to 17 beta is altered after pretreatment with 1,25 or 24,25. Cells were isolated from the costochondral cartilage of male or female rats. Confluent, fourth-passage GC and RC cultures were pretreated with 1,25 or 24,25, respectively, for 24 or 48 h followed by treatment with 17 beta for an additional 24 h. At harvest, cell proliferation ([3H]-thymidine incorporation), differentiation (alkaline phosphatase specific activity [ALPase]), general metabolism ([3H]-uridine incorporation), and proteoglycan production ([35S]-sulfate incorporation) were determined. 1,25 enhanced the inhibitory effect of 17 beta on [3H]-thymidine incorporation by female GC cells; in contrast, no effect was observed in GC cells obtained from male rats. When male RC cells were treated with 17 beta, [3H]-thymidine incorporation was inhibited; however, when these cells were pretreated with 24,25 for 48 h, 17 beta stimulated [3H]-thymidine incorporation 24,25 had no effect on 17 beta-dependent [3H]-thymidine incorporation by female RC cells. 17 beta stimulated ALPase in female GC cells, but had no effect on male GC cells. 1,25 pretreatment of female GC cells inhibited the stimulatory effect of 17 beta on ALPase, but had no effect on ALPase in male GC cultures. 17 beta had no effect on male RC cell ALPase and stimulated ALPase in female RC cells. This was not affected by pretreatment with 24,25. Pretreatment with 1,25 increased the basal level of sulfate incorporation only in female GC. No effect was found in RC cells. These results indicate that pretreatment of rat costochondral chondrocytes with vitamin D metabolites modulate the effect of 17 beta. Although the effect of vitamin D metabolites alone on these chondrocytes is maturation-dependent and not sex-specific, the influence of preincubation with vitamin D metabolites on the effect of 17 beta is hormone-specific, sex-specific, and maturation-dependent.

24,25-Dihydroxyvitamin D 3↗

PubMed1997

Genetic studies of syndromes with severe periodontitis and palmoplantar hyperkeratosis.

The Papillon-Lefèvre and Haim Munk syndromes are characterized by the presence of both palmoplantar hyperkeratosis (PPK) and severe early onset periodontitis. It is the early onset periodontal disease component that distinguishes these from other more common forms of PPK. It has been proposed that the periodontal disease component may be a casual association in individuals with PPK. Genetic syndromes with palmoplantar keratosis and severe ealry onset periodontitis may be due to specific bacterial infections in individuals with PPK. Recently, keratin gene mutations have been identified in several conditions typified by palmoplantar keratosis. The present study sought to test the hypothesis that a keratin gene defect similar to those previously identified in other PPK conditions is responsible for the Haim Munk and the Papillon. Lefèvre syndromes. We have performed genetic linkage studies to test for linkage between polymorphic DNA loci within 2 cytokeratin gene families and the disease phenotype in Haim Munk syndrome and Papillon-Lefèvre syndrome. Families with individuals segregating for the Haim Munk syndrome and the Papillon-Lefèvre syndrome were examined to determine disease status, and genotyped for microsatellite DNA markers closely linked to the acidic (type I) and the basic (type II) cytokeratin genes on chromosomes 12 and 17. Genotype data were evaluated for microsatellite allele homozygosity in affected individuals. Results of these preliminary genetic studies suggest that the gene defect in Haim Munk syndrome is not due to a gene defect in either the type I or the type II keratin gene clusters. These findings suggest that Haim Munk syndrome may be genetically distinct from other more common forms of PPK that have been linked to the cytokeratin gene families, and suggest that mutations in genes other than keratin genes are responsible. Additional family studies are needed to confirm these preliminary findings.

Adult↗

PubMed1997

Tetracycline inhibits Porphyromonas gingivalis lipopolysaccharide-induced lesions in vivo and TNF alpha processing in vitro.

Lipopolysaccharides (LPS) are considered one of the more important virulence factors related to the pathogenesis of periodontal diseases. Based on tetracycline (TTC) ability to bind divalent metal ions, the present study was designed to examine the effect of TTC on P. gingivalis LPS-induced lesions in vivo and on LPS-induced TNF alpha production in vitro. Subcutaneous injection of 50-100 micrograms of P. gingivalis LPS into BALB/C mice induced a visible lesion within 24 h with evident tissue necrosis. Daily systemic administration of TTC for the first 4 d following LPS challenge reduced the size of the lesion, and total inhibition of lesion formation was observed in 75-100% of the treated mice. A non-related broad spectrum antibiotic, ampicillin, or the IL-1 inhibitor ML-20, had no effect on the lesion size. In order to explore some aspects of the mechanism involved, we tested the effect of TTC on LPS-induced TNF alpha secretion by human monocytes in vitro. TTC (1 mM) was found to block LPS-stimulated TNF alpha secretion. Western blotting of monocyte cytoplasmic membranes for membrane-bound TNF alpha show that TTC causes the retention of membrane-associated TNF alpha on monocyte membranes, thereby preventing the release of TNF alpha into the culture media. The results suggest the TTC is an effective in vivo therapy for preventing P. gingivalis LPS-induced subcutaneous lesion formation in the murine model. The mechanism of TTC treatment probably involves blocking the activity of metalloproteinases, including TNF alpha processing enzyme, thereby preventing LPS-induced tissue destruction.

Animals↗

PubMed1997

Subgingival delivery of therapeutic agents in the treatment of periodontal diseases.

This article reviews the current status of controlled local delivery of antibacterial agents in the treatment of periodontitis. The principle of local intrapocket delivery of antibacterial agents and their delivery are discussed. The dosage forms include fibers, film/slabs, and injectable systems, some of which are degradable, while others are not and need to be removed at the termination of the treatment. The antibacterial agents used cover a range of antibiotics as well as antiseptics, and the composition of the delivery systems, their reported use, and the clinical results are summarized. The use of these systems in clinical practice is relatively recent, and therefore their application and integration into the dental office are not yet clearly defined. Clinical applications that have been tested are critically reviewed, and clinical situations in which controlled delivery of antibacterial agents may prove to be clinically useful are suggested for scientific evaluation.

Administration, Topical↗

PubMed1997

Sustained local delivery of chlorhexidine in the treatment of periodontitis: a multi-center study.

The safety and efficacy of a degradable, subgingivally placed drug delivery system containing 2.5 mg chlorhexidine (CHX) were evaluated in a randomized, blinded, multi-center study of 118 patients with moderate periodontitis. A split-mouth design was used to compare the treatment outcomes of scaling and root planing (SRP) alone with the combined use of SRP and the CHX in pockets with probing depths of 5 to 8 mm. The two maxillary quadrants were used for the two treatment arms of the study. Scaling and root planing was performed at baseline only, while the CHX was inserted both at baseline and at 3 months. Clinical and safety measurements including probing depth (PD), clinical attachment level (CAL), and bleeding on probing (BOP) as well as gingivitis, plaque, and staining indices were recorded at baseline, and at 1, 3, and 6 months. The average PD reduction in the CHX-treated sites was significantly greater than in the sites receiving SRP alone at both 3 and 6 months with a mean difference of 0.42 mm (P < or = 0.01) at 6 months. The reduction in CAL at the treated sites was greater than at the SRP sites, although the difference was statistically significant at the 6-month visit only. An analysis of patients with initial probing depths of 7 to 8 mm (n = 56) revealed a significantly greater reduction in PD and CAL in those pockets treated with CHX compared to SRP at both 3 and 6 months. The mean differences between test and control sites at 6 months were 0.71 mm and 0.56 mm PD and CAL respectively.

Adult↗

PubMed1996

Partial expression of the Papillon-Lefèvre syndrome in 2 unrelated families.

The Papillon-Lefèvre syndrome (PLS) is a rare, autosomal recessive trait that is characterized by palmar plantar keratosis (PPK) and severe, early onset periodontitis, affecting both deciduous and permanent dentitions. The clinical presentation of PLS is variable; the disease occurs so infrequently as to limit clinical cases for study. The exception is a few families with extensive consanguinity in which numerous cases occur. Of particular interest to mapping the genetic origin of the syndrome is the co-expression of the major traits of hyperkeratosis and periodontitis, and their severity. In this paper, we report 2 families with multiple affected individuals from geographically remote areas. A large extended family, from the Cochin region of India, currently residing in Israel, in which there is documented consanguinity and a family from the southwest region of Germany. In each family, 1 individual presents with hyperkeratotic lesions with the complete absence of periodontal lesions. Further, the difference in severity of the hyperkeratotic lesions between families is marked, and one sibling in the German family expressed rapid, early onset periodontitis in the absence of PPK. The genetic nature and penetrance of the genetic defect are discussed.

Adult↗

PubMed1996

Protection against endotoxic shock and lipopolysaccharide-induced local inflammation by tetracycline: correlation with inhibition of cytokine secretion.

Septic shock results from excessive stimulation of host immune cells, particularly monocytes and macrophages, by lipopolysaccharide (LPS) released from gram-negative bacteria. Macrophage-derived cytokines, such as tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1 beta), have been identified as central mediators in the pathogenesis of septic shock and the resultant mortality. Therefore, these cytokines were targets for experimental therapy for septic shock. Because of tetracycline's ability to intervene in cellular mechanisms involved in cytokine secretion, we tested the effect of tetracycline on LPS-induced septic shock and inflammatory lesions in mice. Tetracycline was found to protect mice against LPS-induced lethality and to abolish clinical signs of LPS-induced inflammatory lesions. This protection correlates with tetracycline's ability to reduce LPS-induced TNF-alpha levels in serum. Furthermore, tetracycline was found to inhibit LPS-induced TNF-alpha and IL-1 beta secretion, but not cytokine mRNA accumulation, in human monocytes in vitro. The results presented here suggest that tetracycline is a potent drug for LPS-induced pathology and that its mechanism of action involves blockage of posttranscriptional events of cytokine production.

Animals↗

PubMed1996

Prostaglandin E2 secretion, cell maturation, and CD14 expression by monocyte-derived macrophages from localized juvenile periodontitis patients.

Previous studies from our laboratory have demonstrated that freshly isolated peripheral blood monocytes from localized juvenile periodontitis (LJP) patients secrete more prostaglandin E2 (PGE2) after stimulation by lipopolysaccharide (LPS) than do monocytes from healthy subjects. However, it is not clear if the altered function of LJP monocytes is intrinsic to the cells or is induced by the persistent infection of the periodontium. The present study was designed to compare PGE2 secretion by freshly-isolated peripheral blood monocytes (FIM) from LJP and control subjects to in vitro monocyte-derived macrophages (MDM) from the same subjects. We also examined monocyte maturation into macrophage-like cells and the cell-surface expression of the LPS, receptor, CD14 during the culture period. FIM from LJP patients and controls were stimulated by different concentrations of LPS (O to 30 micrograms/ml) for 24 hours. These experiments were performed immediately after cell separation and after 10 days in culture, which allowed differentiation of monocytes into MDM. PGE2 levels in the culture media were determined using a radioimmunoassay. Cell surface expression of CD71, a cell maturation marker, and CD14 were assayed by cell-ELISA in relation to beta-2-microglobulin. LPS-stimulated FIM from LJP patients secreted 3 to 4 times more PGE2 than control FIM at all LPS concentrations tested. After 10 days in culture, the LJP MDM secretion of PGE2 reduced to control MDM level of PGE2 secretion. These levels of PGE2 secretion were comparable to PGE2 secretion from FIM of controls. Cell maturation, as verified by CD71 expression, was found not to differ between the groups. However, the expression of CD14 by LJP FIM was much lower than on control FIM (approximately equal to 50%). After 5 or 10 days in culture, MDM from both control and LJP subjects expressed comparable amounts of CD14. The results suggest that in vitro conditions reverse the hypersensitivity of LJP monocytes to LPS into control levels and CD14 expression is not correlated to the hyper-responsiveness of the cells to LPS.

Adolescent↗