tetracycline and sanguinarine

It is well recognized that periodontal diseases are bacterial in nature. An essential component of therapy is to eliminate or control these pathogens. This has been traditionally accomplished through mechanical means (scaling and root planing [SRP]), which is time-consuming, difficult, and sometimes ineffective. Over the past 20 years, locally delivered, anti-infective pharmacological agents, most recently employing sustained-release vehicles, have been introduced to achieve this goal.. This systematic review evaluates literature-based evidence in an effort to determine the efficacy of currently available anti-infective agents, with and without concurrent SRP, in controlling chronic periodontitis.. In patients with chronic periodontitis, what is the effect of local controlled-release anti-infective drug therapy with or without SRP compared to SRP alone on changes in clinical, patient-centered, and adverse outcomes?. MEDLINE, the Cochrane Central Trials Register, and Web of Science were searched. Hand searches were performed of the Journal of Clinical Periodontology, Journal of Periodontology, and Journal of Periodontal Research. Searches were performed for articles published through April 2002. In addition, investigators contacted editors of the above-mentioned journals and companies sponsoring research on these agents for related unpublished data and studies in progress.. Studies included randomized controlled clinical trials (RCT), and case-controlled and cohort studies at least 3 months long. Therapeutic interventions had to include 1) SRP alone; 2) local anti-infective drug therapy and SRP; or 3) local anti-infective drug therapy alone. Included studies had to report patient-based mean values and measures of variation for probing depth (PD) and/or clinical attachment levels (CAL) for both test and control groups.. Studies were excluded if they: 1) included data from a previously published article; 2) included daily rinsing with chlorhexidine (CHX); or 3) had unclear descriptions of randomization procedures, examiner masking, or concomitant therapies.. For the meta-analysis, PD and CAL were expressed as summary mean effects with 95% confidence intervals (CI) for the effect, and analyzed using a standardized difference between SRP alone and experimental agent groups. The results were assessed with both fixed-effects and random-effects models. Studies were ranked according to the York system.. 1. Thirty-two studies were included (28 RCT, 2 cohort, and 2 case-control), incorporating a total patient population of 3,705 subjects. 2. Essentially all studies reported substantial reductions in gingival inflammation and bleeding indices, which were similar in both control and experimental groups. 3. A meta-analysis completed on 19 studies that included SRP and local sustained-release agents compared with SRP alone indicated significant adjunctive PD reduction or CAL gain for minocycline (MINO) gel, microencapsulated MINO, CHX chip and doxycycline (DOXY) gel during SRP compared to SRP alone. 4. Use of antimicrobial irrigants or anti-infective sustained-release systems as an adjunct to SRP does not result in significant patient-centered adverse events.. 1. In some populations, anti-infective agents in a sustained-release vehicle alone can reduce PD and bleeding on probing (BOP) equivalent to that achieved by SRP alone. 2. No evidence was found for an adjunctive effect on reduction of PD and BOP of therapist-delivered CHX irrigation during SRP compared to SRP alone. 3. Additional RCTs are needed which evaluate the effectiveness of these therapies in all forms of periodontitis. 4. The study protocol for future RCTs should include appropriate statistical analyses and complete data sets to facilitate future evidence-based reviews. 5. Alternative surrogate parameters to PD and CAL need to be identified and validated such as microbial, inflammatory, or tissue-destructive markers that could be used in conjunction with clinical parameters to help determine the patient's response to emerging technologies that target the infectious and/or inflammatory aspects of periodontitis. 6. Future Phase IV clinical trials should be designed that evaluate local anti-infective therapies in conjunction with SRP in a manner consistent with current standards of care and evaluate cost-effectiveness. 7. The use of local anti-infective agents in at-risk patient populations and for the treatment of at-risk disease sites needs to be validated in randomized controlled clinical trials. 8. Several local anti-infective agents combined with SRP appear to provide additional benefits in PD reduction and CAL gain compared to SRP alone. The decision to use local anti-infective adjunctive therapy remains a matter of individual clinical judgment, the phase of treatment, and the patient's status and preferences.

Topics: Alkaloids; Anti-Bacterial Agents; Anti-Infective Agents, Local; Benzophenanthridines; Chlorhexidine; Delayed-Action Preparations; Dental Scaling; Doxycycline; Humans; Isoquinolines; Metronidazole; Minocycline; Periodontitis; Tetracycline

Antibiotic resistance has prompted efforts to discover antibiotics with novel mechanisms of action. FtsZ is an essential protein for bacterial cell division, and has been viewed as an attractive target for the development of new antibiotics. Sanguinarine is a benzophenanthridine alkaloid that prevents cytokinesis in bacteria by inhibiting FtsZ self-assembly. In this study, a series of 5-methylbenzo[c]phenanthridinium derivatives were synthesized and evaluated for antibacterial activity against Staphylococcus aureus and Enterococcus faecalis. The data indicate that the presence of a 1- or 12-phenyl substituent on 2,3,8,9-tetramethoxy-5-methylbenzo[c]phenanthridinium chloride significantly enhances antibacterial activity relative to the parent compound or sanguinarine.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Benzophenanthridines; Cytoskeletal Proteins; Enterococcus faecalis; Isoquinolines; Microbial Sensitivity Tests; Phenanthridines; Staphylococcus aureus

The effectiveness of an ideal antimicrobial agent depends on its ability to kill microbes with minimal toxicity to host cells. Depending on the treatment regimen, antimicrobial agents come into contact with host cells for various intervals of time. Sanguinarium (SANG), chlorhexidine (CHX) and tetracycline (TET) are 3 antimicrobial agents frequently used in the management of periodontal infections. However, their effects on host immune cells during different treatment regimens are not known. Due to their ability to serve as the first line of host defense against microbial infections, we have compared the effects of these antimicrobial agents on human neutrophil functions and viability. The results show that SANG is not lytic to neutrophils from peripheral blood or crevicular fluid, at all concentrations tested. However, exposures of neutrophils to very low concentrations of SANG (0.001%) inhibits neutrophil chemotaxis, oxidative metabolism and degranulation within 5 min. Increasing the exposure time results in a similar inhibition of neutrophil functions, albeit at 50-100 fold lower concentrations of SANG. CHX rapidly disrupts the cell membrane of both crevicular and peripheral blood neutrophils at concentrations above 0.005% within 5 min, and inhibition of all neutrophil functions is due to its lytic properties. While TET is least toxic to neutrophils, a dose dependent inhibition of neutrophil functions is dependent on the calcium concentrations of the cellular environment, and is observed only above 0.04% or higher concentrations in the absence of calcium. The data suggest that a critical cumulative concentration of these drugs is essential for their toxicity and inhibition of neutrophil functions. Therefore, both the length of exposure and the dose of the drug both are critical while considering the effectiveness of SANG, CHX or TET in the treatment of infections. Furthermore, due to differences in their mechanisms of action, the consequences of their effects on neutrophils may have significant bearing on tissue pathology as well as on their therapeutic efficacy.

Topics: Adult; Alkaloids; Anti-Bacterial Agents; Anti-Infective Agents, Local; Benzophenanthridines; Cell Degranulation; Cell Survival; Cells, Cultured; Chemotaxis, Leukocyte; Chlorhexidine; Dose-Response Relationship, Drug; Humans; Isoquinolines; Microbial Sensitivity Tests; Neutrophils; Respiratory Burst; Superoxides; Tetracycline

Inflammatory periodontal diseases are related to dental plaque formation. Increase in the perfusion of the inflamed tissue results in increased oxygen supply. Although oxygen has healing effects, it is bound to be a mediator of peroxidation in biological membranes. Chemotherapeutic agents such as chlorhexidine, listerine, sanguinarine, and cetylpridinium chloride and oral antibiotics such as tetracycline HCl and doxycyline were tested for their antioxidative activities. While doxycycline has the highest antioxidant activity in lower volumes (0.1 ml), sanguinarine, listerine and a pace after them, tetracycline HCl, had similar effects in higher volumes (0.3 and 0.4 ml). The results showed that in addition to their antiseptic or antimicrobial effects, these preparations have an antioxidative activity against spontaneous oxidation.

Topics: Alkaloids; Animals; Anti-Infective Agents, Local; Antioxidants; Benzophenanthridines; Brain; Cattle; Cetylpyridinium; Chlorhexidine; Dental Plaque; Doxycycline; Drug Combinations; Gingivitis; Isoquinolines; Malondialdehyde; Membranes; Mouthwashes; Oxidation-Reduction; Peroxides; Salicylates; Terpenes; Tetracycline