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S Offenbacher

Publications and source records attributed to S Offenbacher.

At least 91 records · Page 5Linked to original sources
PubMed1993

Diagnostic potential of host response mediators.

This review summarizes the data which relate the validation and application of host response markers as diagnostic tests for periodontal diseases. Practical considerations regarding the general application and evaluation of a diagnostic test for periodontal disease are presented. Experiments which have documented the performance of host response markers as diagnostic measures of disease activity in terms of sensitivity, specificity, and predictive values are summarized. Particular emphasis is placed on the diagnostic potential of gingival crevicular fluid (GCF) components. The considerable body of evidence supporting the potential application of GCF-PGE2 levels for predicting episodes of disease progression and reflecting disease activity is summarized and placed into perspective for the development of future diagnostic tools.

Biomarkers↗
PubMed1993

Effects of a combination therapy to eliminate Porphyromonas gingivalis in refractory periodontitis.

This report describes the clinical and microbiological features of 30 refractory patients and their response to a combined local and systemic therapy at 6 weeks and 3 years following treatment. The refractory treatment protocol (RefTx) consisted of a 2-week regimen of amoxicillin/clavulanate potassium in conjunction with professional, intrasulcular delivery of povidone iodine, and chlorhexide mouthwash rinses b.i.d. Eighty-seven percent of the patients had favorable clinical responses to the RefTx and could be divided into 3 groups (A, B, C) based upon initial flora patterns and the shifts that occurred following treatment. Pretreatment prevalence of Porphyromonas gingivalis (P.g.) was 36.7%. The RefTx was effective in reducing P.g. below detection levels in 10 of the 11 positive patients at P < 0.01; each of these 10 patients (Group A) demonstrated significant gain in attachment. Other black-pigmented Bacteroides species (OBP) were isolated from 70% of the patients at baseline. Nine of these patients did not harbor P.g., showed clinical improvement upon treatment, and were OBP negative following treatment (Group B). Group C patients (7) demonstrated clinical improvement with therapy and did not fit into either Group A or B based upon microbial patterns. Group D patients (4) did not show clinical improvement with 3 patients harboring either P.g. or OBP after treatment. The RefTx was effective at reducing probing pocket depth with a 56% decrease in the number of pockets greater than 6 mm at 6 weeks. This was accompanied by an overall gain of > or = 1 mm of probable attachment in 45% of all sites. The clinical effects of the RefTx were shown to persist at 34.3 months with an apparent attachment gain of > or = 1 mm in 41.2% of sites. These data suggest that P.g. and OBP are important pathogens in refractory periodontitis and that the RefTx protocol is an acceptable, non-invasive alternative for the management of these patients.

Adult↗
PubMed1993

Modulation of host PGE2 secretion as a determinant of periodontal disease expression.

An increasing body of evidence supports the concept that host-produced PGE2 mediates much of the tissue destruction that occurs in periodontal disease. PGE2 levels within the crevicular fluid can serve as a static assessment of ongoing disease activity; i.e., rate of attachment loss and bone resorption. New insights into the mechanisms that regulate PGE2 synthesis provide an altered paradigm of periodontal disease which places the emphasis on host response, rather than the bacterial etiology, as the principal determinant of disease expression. We described a PGE2 host response model as a hypothetical framework to discuss new, possible explanations for host susceptibility to periodontal disease.

Animals↗
PubMed1993

Defective chemotaxis and calcium response in localized juvenile periodontitis neutrophils.

Localized juvenile periodontitis (ljp) is an early onset form of periodontal disease characterized by unique localization to first molars and incisors and a high prevalence of neutrophil abnormalities, particularly chemotaxis. The intracellular transduction mechanisms that follow receptor-ligand coupling on the neutrophil surface and lead to chemotaxis are not clearly established. Chemotaxis and phagocytosis are modulated by a variety of receptors and involve several activation pathways; the role of intracellular calcium as a presumptive second messenger and mediator of these events is well established. The putative effector mechanisms for the chemotactic receptor of neutrophils also include the possible activation of a phospholipase, protein kinase C, methyltransferase, or adenylate cyclase. In normal neutrophils, a phosphoinositide pathway initiated by phospholipase C, which results in the activation of protein kinase C via diacylglycerol and the generation of IP3, has been implicated. In order to better understand the stages of neutrophil transduction, fluorescent probes were used to monitor neutrophil calcium changes. Chlorotetracycline (CTC) was used as an indirect probe of intracellular membrane-bound pool of calcium stores, and Quin-2 was used to monitor cytosolic free calcium levels of FMLP stimulated normal and LJP neutrophils. The results indicate that the early phase of the calcium response affiliated with the release of intracellularly sequestered calcium appears intact in LJP neutrophils, as the CTC fluorescence changes were similar to control values. The second phase of the calcium response, associated with membrane channel activation and an influx of extracellular calcium, appeared compromised in the neutrophils of the LJP population.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Effects of NSAIDs on beagle crevicular cyclooxygenase metabolites and periodontal bone loss.

This investigation focuses on the changes in the concentrations of cyclooxygenase (CO) products present within the crevicular fluid in naturally-progressing periodontitis in the beagle and the effects of various non-steroidal anti-inflammatory drugs (NSAIDs) on these metabolite levels and disease progression. Six groups of 5-6 beagles with periodontitis were followed for 6 months to determine the pretreatment rate of radiographic bone loss. At baseline, groups of animals were placed on soft chow to promote disease progression. Groups were treated with either placebo, three different formulations of systemic ibuprofen, systemic naproxen or topical flurbiprofen. During the 6-month treatment phase, crevicular fluid (CF) samples and radiographs were taken at regular intervals. Radioimmunoassay of CF samples from untreated animals demonstrated a steady increase in prostaglandin E2 (PGE2) over baseline values. At 1 month, CF-PGE2 levels increased 2-fold over baseline and, by 6 months, had reached a 5- to 6-fold elevation. Crevicular fluid thromboxane B2 (CF-TxB2) levels rapidly reached a 4- to 5-fold peak over baseline at 1 month and subsequently dropped to a 2-fold elevation for the remainder of the study. The rate of bone loss (BLOSS) in untreated animals increased 38% during the 6-month period, as compared to baseline pretreatment BLOSS rates. Overall, there was a significant depression in the CF levels of both PGE2 and TxB2 in all NSAID-treated groups. All NSAID treatments significantly retarded BLOSS, ranging from 21.0-36.9% of the control BLOSS rate. Furthermore, CO activation represents a major regulatory step in bone destruction and may thereby serve as an important site for pharmacological modulation.

Administration, Oral↗
PubMed1992

Neuropeptide Y and coronary vasoconstriction: role of thromboxane A2.

We previously reported that coronary constriction following neuropeptide Y (NPY) was alleviated by cyclooxygenase blockade. To determine the role of thromboxane A2 (TxA2), anesthetized dogs received two paired doses of NPY given 2 h apart. Nine control dogs received NPY alone. Nine test dogs received one of three TxA2 receptor antagonists given between the doses of NPY. Also, five dogs received NPY during which prostaglandins were measured. In controls, NPY decreased coronary blood flow and increased aortic pressure; coronary resistance was increased significantly. Heart rate fell, and myocardial oxygen consumption was unchanged. Thromboxane receptor blockers significantly relieved the coronary constrictor effect of NPY. The reduction in coronary blood flow was blunted, while heart rate, first derivative of left ventricular pressure, and myocardial oxygen consumption were unchanged. Alleviation by TxA2 receptor blockade paralleled that reported for cyclooxygenase inhibitors. Also, significant increases in coronary venous TxA2 were seen at the time of maximal increases in coronary resistance, while prostacyclin was unchanged. In summary, TxA2 appears to mediate part of the coronary constrictor effect of NPY.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1990

Inhibition of human periodontal prostaglandin E2 synthesis with selected agents.

Considerable evidence has demonstrated the importance of PGE2 synthesis in the pathogenesis of periodontal disease. Although various cyclooxygenase inhibitors have been known to block periodontal PGE2 synthesis and prevent disease progression in animal models, there are few reports comparing relative efficacies of various inhibitors of arachidonic acid (ARA) metabolism. We have developed a sensitive in vitro assay to measure PGE2 synthesis in periodontal tissues. The apparent IC50 values (i.e. the concentration of drug which causes 50% inhibition of maximum PGE2 synthesis) have been determined for a series of arachidonic acid analogues as well as competitive and non-competitive cyclooxygenase inhibitors. Periodontal tissue homogenates were incubated in the presence of 3H-arachidonic acid for 45 min at 37 degrees C. Inhibitors were tested at 10(-10)-10(-4) M and at zero concentration to measure conversion of 3H-arachidonate to 3H-PGE2. Log or half log dilutions of inhibitors were tested in triplicate for each assay. Radiolabeled PGE2 was extracted from homogenates, purified by reverse phase chromatography and quantitated by double antibody capture. RIA was performed on each homogenate to determine the amount of endogenous unlabeled PGE2 present in the sample to correct for antibody capture recovery. The apparent IC50 values were determined for each drug by averaging two or more replicate assays. Specific total enzymatic activity of periodontal tissue homogenates was typically 5-11 pg PGE2/min/mg tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

Arachidonic Acid↗
PubMed1990

Neutrophil surface protein markers as indicators of defective chemotaxis in LJP.

Abnormalities of neutrophil function have been highly correlated with severe, early onset periodontal diseases. Nonetheless, the identification of these patients and diagnosis of specific disease states, such as LJP or prepubertal periodontitis, are difficult and costly. In this report, the identification and quantification of neutrophil cell surface markers specific to LJP patients with neutrophil chemotaxis defects are described. GP110 and FMLP receptors were quantified by flow cytometry on neutrophils from LJP patients with neutrophil chemotaxis defects, LJP patients without chemotaxis defects, other patients with primary neutrophil chemotaxis defects, and controls. Results suggest that reduction of GP110 and FMLP receptor on neutrophils is specific for LJP patients who exhibit neutrophil chemotaxis abnormalities.

Adolescent↗
PubMed1989

Changes in cyclooxygenase metabolites in experimental periodontitis in Macaca mulatta.

The four principal metabolites of cyclooxygenase (CO) were examined during the progression of experimental periodontitis in the rhesus monkey Macaca mulatta. Thirty-two monkeys were divided in four disease-matched groups. Three groups were treated with flurbiprofen, a potent CO inhibitor, at either 0.027, 0.27 or 7.1 mg/kg/day delivered systemically by a subcutaneously-implanted osmotic mini-pump. We have previously described the findings indicating that flurbiprofen treatment significantly retarded clinical attachment loss (ALOSS), redness and radiographic bone loss (BLOSS). This investigation focuses on the changes in CO metabolites which occur during disease progression of ligature-induced periodontitis and on the dose-response relationship of flurbiprofen, as it relates to disease inhibition and the suppression of ARA metabolites within the crevicular fluid (CF). In untreated animals there was a statistically significant 3-fold increase in CF levels of prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) at 3 months, as compared to baseline, which positively correlated with increases in redness, bleeding, ALOSS and BLOSS. CF-PGE2 and TxB2 levels reached a 6-fold peak at 6 months and returned to baseline by 12 months. Flurbiprofen (Fb) prevented the 3-month rise in TxB2, but did not affect the increase in PGE2. At 6 months, Fb administration caused a dose-dependent inhibition of both PGE2 and TxB2. Probit analysis of the dose-response data revealed that the concentration of Fb which caused a 50% inhibition of CF-TxB2 level (the IC50 value for TxB2 synthesis) was approximately two logs lower than the IC50 value for PGE2 synthesis, i.e. TxA2-IC50 = 0.013 vs. PGE2-IC50 = 1.35 mg flurbiprofen/kg/d. The slopes of the PGE2 and TxB2 inhibition curves were identical, consistent with a similar mechanism or singular enzyme for the site of action of Fb inhibition of CO activity. However, the kinetics and sensitivity of Fb inhibition were significantly different for the CO activity responsible for TxB2 and PGE2 synthesis, perhaps due to different compartmentalization of CO within different cell types.

Animals↗
PubMed1988

Microbial colonization patterns of loosely adherent subgingival plaque in adult periodontitis.

Periodontal plaque is a complex bacterial ecosystem that carries an innate history of colonization, selection and maturation. Detailed examination of this balanced environment can reveal developmental sequences and certain interrelationships, much like an archeological record, that can provide insight in the understanding of plaque formation and maturation. For the present investigation, methods are employed which enable the retrospective elucidation of the historical data of plaque development and the nature of bacterial interactions. Nonparametric statistical methods are used to analyze risk, agreement and interdependence, following analytical techniques which are well established in medical epidemiology, but not generally employed in dentistry. The fundamental concept is that many organisms which are present in plaque prefer or require a pre-existing bacterial miliue for colonization and growth to steady-state level. Plaque samples and Ramfjord attachment level measurements were obtained from 60 adult periodontitis patients. Loosely adherent plaque was sampled and different morphotypes were enumerated by darkfield microscopy. The colonization of small spirochetes (S-SP) within the loosely adherent plaque was essential for the colonization of medium spirochetes (M-SP), odds ratio = 15.7 and filaments (FIL), odds ratio = 22.2. Thus, a temporal colonization sequence is inferred for FIL and M-SP, both requiring S-SP as a prerequisite morphotype. Medium spirochetes, in turn, are required for fusiform (FUS) colonization. M-SP also enhance the colonization of FIL and large motile rods (L-MO-R) within the loosely adherent plaque. These morphotypes were inferred to be sequentially interdependent, each preferring or requiring the presence of the preceding morphotype.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

Refractory periodontitis: mixed infection with Bacteroides gingivalis and other unusual Bacteroides species. A case report.

Host immune response and the predominant subgingival microflora were evaluated in a 47-year-old male exhibiting severe, recurrent periodontitis. The patient's neutrophils were chemotactically elevated but other functions were within normal limits. Significantly, Bacteroides gingivalis and Bacteroides zoogleoformans constituted 80% of the cultivable microflora and total cell count in subgingival plaque. The remainder of the cultivable microbiota was comprised of Fusobacterium nucleatum and Haemophillis aprophillis. The present study provides additional evidence for an association between B. gingivalis and severe, recurrent periodontal disease.

Bacteroides↗
PubMed1987

Association of an abnormality of neutrophil chemotaxis in human periodontal disease with a cell surface protein.

Localized juvenile periodontitis (LJP) is characterized by severe, early-onset, molar and incisor bone loss; neutrophil chemotaxis disorders; and a high prevalence of Actinobacillus actinomycetemcomitans infection. LJP is further characterized by significant familial aggregation of the disease. Recent work in our laboratory has demonstrated the selective depletion of a surface glycoprotein of 110,000 Mr (GP110) from LJP neutrophils by using surface labeling with [14C]formaldehyde and autofluorography. The function of GP110 is unknown; however, it does not appear to be a chemotactic factor receptor. Rather, it is bound by a monoclonal antibody (NCD-1) that recognizes a neutrophil differentiation antigen and which itself alters neutrophil chemotactic and secreting functions. To quantify GP110 on LJP and normal neutrophils, fluorescein-labeled NCD-1 was bound to neutrophils and the amount of fluorescence was evaluated by using cytofluorography. Our results indicate that there is a quantifiable reduction (40%) of GP110 on the surface of LJP and GJP neutrophils, compared with controls. Other patients with neutrophil defects express normal quantities of GP110, suggesting disease specificity. Our data suggest that GP110 may be a useful disease marker for LJP and may provide a useful probe for the study of neutrophil chemotactic function and dysfunction.

Aggressive Periodontitis↗