Clinical studies on the management of periodontal diseases utilizing subantimicrobial dose doxycycline (SDD)
ABSTRACT Periodontitis, the most common chronic inflammatory condition known to mankind, is a disease that results in the destruction of tooth supporting tissues. Periodontitis is initiated by a bacterial biofilm on the tooth surface below the gingival margin. Until fairly recently it was assumed that the bacteria were the primary cause of tissue destruction, however, a large body of research has revealed that it is the patient's immune response that is actually responsible for the majority of the breakdown of tooth supporting tissues. Contemporary thinking suggests that successful, long term management of chronic periodontitis may combine both local mechanical and antimicrobial strategies to reduce the microbial bio-burden along with modulation of the host, patient's excessive, immuno-inflammatory response to the bacterial exposure known as host modulatory therapy (HMT). Based on extensive literature documenting the enzymatic inhibition and related anti-inflammatory properties of the tetracyclines, a new drug was developed as a host modulatory agent and approved by the United States Food and Drug Administration (FDA) for use as an adjunct to conventional scaling and root planing for the treatment of chronic periodontitis. A subantimicrobial dose of doxycycline (SDD) at 20 mg (Periostat(®)) has been found to be a safe and effective adjunct when taken twice daily for at least 3 months and up to 24 months in randomized placebo controlled clinical trials. Periostat(®) is currently the only FDA approved inhibitor of the matrix metalloproteinases implicated in the plaque-induced pathologic degradation of connective tissue collagen of the periodontal supporting structures. This review paper begins with a brief description of the disease process known as periodontitis followed by an extensive review of the Phase I-IV clinical trial data that established the safety and efficacy of sub-antimicrobial dose doxycycline (SDD) as an adjunct to scaling and root planing for the treatment of periodontitis.
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ABSTRACT: Among the mammalian matrix metalloproteinases (MMPs), MMP-1,–3 and -13 are collagenases. Particularly, MMP-13 is important for the degradation of major collagens in cartilage under certain pathological conditions such as osteoarthritis. To establish a potential therapeutic strategy for cartilage degradation disorders, the effects of 11 ginseng saponins (ginsenosides Rb1, Rb2, Rc, Rd, Re, Rf, Rg1, Rg3, Rg5, Rk1 and F4) on MMP-13 induction were examined in a human chondrocyte cell line, SW1353. Among these, several saponins including ginsenoside Rc, Rd, Rf, Rg3 and F4 were found to inhibit MMP-13 expression in IL-1β-treated SW1353 cells at non-cytotoxic concentrations (1–50 μM). The most prominent inhibitors were ginsenosides F4 and Rg3. Ginsenoside F4 inhibited MMP-13 expression 33.5% (P<0.05), 57.9% (P<0.01) and 90.0% (P<0.01) at 10, 30 and 50 μM, respectively. Significantly, ginsenoside F4 was found to strongly inhibit activation of p38 mitogen-activated protein kinase in signal transduction pathways (86.6 and 100.0% inhibition at 30 and 50 μM, P<0.01). The MMP-13 inhibitory effect was also supported by the finding that ginsenosides F4 and Rg3 reduced glycosaminoglycan release from IL-1α-treated rabbit joint cartilage culture to some degree. Taken together, these results indicate that several ginsenosides inhibit MMP-13 expression in IL-1β-treated chondrocytes. Ginsenoside F4 and Rg3 blocked cartilage breakdown in rabbit cartilage tissue culture. Thus, it is suggested that certain ginsenosides have therapeutic potential for preventing cartilage collagen matrix breakdown in diseased tissues such as those found in patients with arthritic disorders.European journal of pharmacology 01/2013; DOI:10.1016/j.ejphar.2013.12.035 · 2.68 Impact Factor
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ABSTRACT: The use of antibiotics in nonsurgical periodontal treatment is indicated in cases in which scaling and root planing present important limitations. However, their use is controversial due to the secondary effects associated with them and the disagreements regarding their prescription. The aim of this study is to determine the effectiveness of systemic antibiotics in the management of aggressive and chronic periodontitis. The study was based on a search of randomized, controlled clinical trials. Common data were concentrated and evaluated by means of an analysis of variance (ANOVA), and a meta-analysis of the results was performed. The meta-analysis (P < 0.05, 95% confidence interval, post hoc Bonferroni) determined that the supplementation of nonsurgical periodontal therapy with a systemic antibiotic treatment-amoxicillin with clavulanic acid and metronidazole or subantimicrobial dose doxycycline-provides statistically significant results in patients with aggressive or chronic periodontitis under periodontal treatment, whilst increasing the clinical attachment level of the gingiva and reducing periodontal probing depth.01/2012; 2012:581207. DOI:10.5402/2012/581207
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ABSTRACT: Matrix metalloproteinase-13 (MMP-13) plays a critical role in degrading major collagens in human cartilage under some pathological conditions such as osteoarthritis. To establish the therapeutic potential against cartilage degradation, the effects of 12 naturally-occurring triterpenoids and steroids on MMP-13 induction were examined in the human chondrocyte cell line, SW1353. They included coreanoside F1, suavissimoside R1, spicatoside A, 25(S)-ruscogenin, methyl protogracillin, hederagenin, loniceroside A, loniceroside B, loniceroside C, smilaxin A, smilaxin C, and ursolic acid. Among these, only spicatoside A and 25(S)-ruscogenin were found to inhibit MMP-13 expression in IL-1β-treated SW1353 cells at a pharmacologically-relevant concentration of 10 μM. These effects were also supported by the finding that spicatoside A (20 μM) reduced glycosaminoglycan release from IL-1α-treated rabbit joint cartilage culture to some degree. When the cellular mechanisms of action of spicatoside A in MMP-13 inhibition were investigated, the blocking point was not found among the MMP-13 signaling molecules examined such as mitogen-activated protein kinases, activator protein-1, and nuclear transcription factor-κB. Instead, spicatoside A was found to reduce MMP-13 mRNA stability. All of these findings suggest that spicatoside A and 25(S)-ruscogenin have a therapeutic potential for protecting against cartilage breakdown in arthritic disorders.Archives of Pharmacal Research 02/2015; 38(6). DOI:10.1007/s12272-015-0581-z · 1.75 Impact Factor