Subantimicrobial dose doxycycline efficacy as a matrix metalloproteinase inhibitor in chronic periodontitis patients is enhanced when combined with a non-steroidal anti-inflammatory drug.

BACKGROUND: Administration of subantimicrobial dose doxycycline (SDD) to chronic periodontitis (CP) patients has repeatedly been found to reduce mammalian collagenase and other matrix metalloproteinase (MMP) activity in gingival tissues and crevicular fluid, in association with clinical efficacy, without the emergence of antibiotic-resistant bacteria either orally or extra-orally. More recently, SDD adjunctive to repeated mechanical debridement resulted in dramatic clinical improvement in patients (>50% smokers) with generalized aggressive periodontitis. As an additional pharmacologic approach, non-steroidal anti-inflammatory drugs (NSAIDs) can reduce gingival inflammation and alveolar bone resorption, at least under experimental conditions. In the current study, we determined the effect of administering a combination (combination) of these two host-modulating drugs (SDD plus low-dose NSAID) to CP patients, on selected neutral proteinases in gingiva, enzymes believed to mediate periodontal breakdown. Earlier preliminary studies in humans with bullous pemphigoid, which is also associated with excessive levels of host-derived proteinases including MMPs, indicated improved clinical efficacy of combination therapy. METHODS: Nineteen CP patients, scheduled for mucoperiosteal flap surgery bilaterally in the maxillary arch, were randomly distributed into three experimental groups administered either 1) low-dose flurbiprofen (LDF) alone, 50 mg q.d.; 2) SDD (20 mg b.i.d.) alone; or 3) a combination of SDD plus LDF (combination). The gingival tissues were biopsied during surgery from right and left maxillary posterior sextants, before and after a 3-week regimen of medication, respectively. The tissues were then extracted, the extracts partially purified, then analyzed for the endogenous proteinase inhibitor, alpha1-PI, and its breakdown product, and for host-derived matrix metalloproteinases (i.e., collagenases, gelatinases) and neutrophil elastase activities. RESULTS: Short-term therapy with SDD alone produced a significant reduction and LDF alone produced no reduction in host-derived neutral proteinases. However, the combination therapy produced a statistically significant synergistic reduction of collagenase, gelatinase, and serpinolytic (alpha1-PI degrading) activities (69%, 69%, and 75% reductions, respectively) and a lesser reduction of the serine proteinase, elastase (46%). CONCLUSIONS: Consistent with previous studies on animal models of chronic destructive disease (e.g., rheumatoid arthritis), the SDD and NSAID combination therapy synergistically suppressed MMP and other neutral proteinases in the gingiva of CP patients. A mechanism, suggested by earlier animal studies, involves the NSAID, in the combination regimen, increasing the uptake of the tetracycline-based MMP inhibitor in the inflammatory lesion, thus synergistically enhancing the efficacy of this medication.

Differences in risk factors among clinical types of oral candidiasis in the Women's Interagency HIV Study.

OBJECTIVES: The purpose of this study was to determine the prevalence and concurrence/associations of oral candidiasis types and multiple risk factors in women. STUDY DESIGN: A cross-sectional analysis of baseline data for 577 human immunodeficiency virus (HIV)-seropositive and 152 HIV-seronegative women from the Women's Interagency HIV Study was conducted. Pseudomembranous candidiasis (PC) and erythematous (EC) candidiasis, angular cheilitis (AC), and denture stomatitis (DS) were studied, and bivariate and multivariate regression analyses were performed. RESULTS: Prevalences were 8% for PC, 7% for EC, 18% for DS, and 3% for AC; all except AC usually occurred alone. HIV seropositivity was associated with PC, EC, and DS, but not AC. Among HIV-seropositive women, low CD4 cell counts were associated with PC, but not with EC or DS. Heroin/methadone use was associated with PC and EC; salivary hypofunction was associated with PC; high viral load was associated with EC, and poor oral hygiene, with EC and DS. CONCLUSIONS: Risk factors varied among candidiasis types, suggesting differences in pathogenic mechanisms and usefulness as markers of HIV infection/progression.