Faculty Bibliography

Epithelia are key barriers to infections. In periodontal disease, the gingival sulcular epithelium becomes ulcerated. In this report, we test the hypothesis that short-chain carboxylic acids (SCCA) inhibit keratinocyte proliferation, increase necrosis and apoptosis, and may thus promote ulceration. SCCA produced by bacteria are present at millimolar concentrations in the periodontal pockets of subjects with periodontal disease. SCCA concentrations are higher in subjects with severe disease than in those with mild disease, and are not detectable in healthy subjects. Cell proliferation is critical for maintenance of epithelial barrier function. All SCCA tested, when neutralized, decreased epithelial cell proliferation (as measured by 3H-thymidine incorporation) in a dose-dependent manner. We found that epithelial cell viability decreased with increasing SCCA concentrations, accounting at least partly for the decreased 3H-thymidine incorporation. For all conditions we tested, SCCA-induced apoptosis preceded and exceeded necrosis. While the molecular mechanism(s) for these effects remain to be determined, the results indicate that SCCA derived from caries- or periodontal disease-associated bacteria could alter gingival barrier function.

Earlier studies in our laboratories demonstrated that particles of a number of snack foods that are retained on the dentition accumulate fermentable sugars and short-chain carboxylic acids (SCCA; acetic, formic, lactic, and propionic) to different degrees. The present study was undertaken to test the hypothesis that the accumulated SCCA can induce a gingival inflammatory response. Five periodontally and medically healthy subjects were given portions of plain doughnuts (high SCCA levels) or oatmeal cookie (low SCCA), or had the SCCA applied directly to the gingival margins of designated teeth. Subjects were given wax to chew, or nothing, as controls. Inflammation was assessed by measurements of subgingival temperature, flow rates of gingival crevicular fluid (GCF), and neutrophil emigration into GCF. Subgingival temperatures of the maxillary gingiva rose by 1.32 +/- 0.30 degrees C (mean +/- SE) 5 min after the subjects consumed the doughnuts and remained elevated for at least 1 hr. These values were significantly higher than those obtained from subjects after ingestion of oatmeal cookies (0.63 +/- 0.17 degree C; p < 0.01), consistent with the low levels of SCCA in the retained cookie particles. Wax chewing elicited a similar response, indicating a masticatory effect on the gingiva. Gingival temperatures in the unchallenged controls remained unchanged. Neutrophil emigration into the GCF was significantly elevated in subjects after doughnut consumption. Rinses with a solution of SCCA, or application of the SCCA to the gingiva, also brought about significant elevations in subgingival temperature and neutrophil emigration. The findings describe the inflammatory effects of food ingestion on the gingiva of healthy human subjects, and support the hypothesis that SCCA in the particles of retained food are at least partly responsible for the observed responses.

Evidence-based clinical practice integrates the best available evidence with clinical expertise. This article presents a clinical case scenario and, using a four-step, evidence-based approach, demonstrates how to (1) ask an evidence-based question; (2) search MEDLINE for the best evidence; (3) critically appraise the evidence; and (4) apply the evidence to the patient. The procedure is demonstrated with the sample question, Does bleaching of bonded porcelain veneers increase marginal leakage? A MEDLINE search strategy was developed for synonyms of the key words that best identify the problem, the intervention, and the outcome. The synonyms were combined using the Boolean operator "or" to identify a "sensitive" (i.e., inclusive) universe of 140,000 journal articles. These categories were then combined using the Boolean operator "and" to identify the most "specific" (i.e., exclusive) four articles from among the 140,000. Finally, to find the best evidence, the articles were limited to "humans" and "randomized controlled trials." This identified one article. Critical appraisal of the limited data in this one article indicates that the methods are valid and statistically significant, but because of the methods employed, may not be clinically important. Evidence-based methods take one to the edge of the available information universe in about 15 minutes. The results can be both exhilarating and sobering. They can indicate the depth or limits of available information and suggest gaps in the knowledge-base that require further study. Most importantly, however, the results allow practitioners to communicate incisively and truthfully with patients and to make more informed clinical choices.

Short-chain carboxylic acids are the metabolic by-products of pathogenic anaerobic bacteria and are found at sites of infection in millimolar quantities. We previously reported that propionic acid, one of the short-chain carboxylic acids, induces an increase in intracellular Ca2+ ([Ca2+]i) in human neutrophils. Here we investigate the effect of propionic acid on superoxide generation in human neutrophils. Propionic acid (10 mm) induced inositol 1,4, 5-trisphosphate (IP3) formation and a rapidly transient increase in [Ca2+]i, but not superoxide generation, whereas 1 microm formylmethionyl-leucyl-phenylalanine (fMLP), a widely used neutrophil-stimulating bacterial peptide, stimulated not only IP3 formation and Ca2+ mobilization but also superoxide generation. The IP3 level induced by propionic acid was slightly lower than that induced by fMLP. The transient increase in [Ca2+]i induced by propionic acid immediately returned to the basal level, whereas a sustained increase in [Ca2+]i, which was higher than the basal level, following a transient increase in [Ca2+]i was induced by fMLP. The peak level induced by propionic acid was lower than that with fMLP. In the absence of extracellular Ca2+, thapsigargin, a potent inhibitor of endoplasmic reticulum Ca2+-ATPase, induced an increase in [Ca2+]i even after propionic acid stimulation, but not after fMLP. The Ca2+ ionophore A23187 and thapsigargin induced superoxide generation by themselves. Propionic acid enhanced the superoxide generating effect of A23187 and thapsigargin. These results suggest that Ca2+ mobilization induced by propionic acid is much weaker than that with fMLP, and propionic acid is able to generate superoxide in the presence of a Ca2+ ionophore and a Ca2+ influx activator.