Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0031099 (periodontitis)
 12,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is no doubt that plaque bacteria are necessary to initiate disease and drive the chronic inflammatory response in the periodontal tissues. At the same time, there is strong evidence that destructive processes occurring as part of the host inflammatory response are responsible for the majority of the hard- and soft-tissue breakdown leading to the clinical signs of periodontitis. The characteristic clinical signs of chronic periodontitis occur mainly as a result of activation of host-derived immune and inflammatory defense mechanism. IL-1 and TNF induce expression of other mediators that amplify the inflammatory response, such as prostaglandins, and lead to production of lytic enzymes and stimulate the production of chemokines. Investigations on the soluble protein delivery of antagonists to IL-1 and TNF in animal models have shown promising results. Collectively, the clinical, radiographic, and biochemical findings of these experiments show that IL-1 and TNF-alpha antagonists block the progression of the inflammatory cell infiltrate towards the alveolar crest and the recruitment of osteoclasts, and prevent the periodontal lesions may destroy the soluble cytokine antagonists prior to their peak activity, which may necessitate more frequent administration of the active agents to the defects. Thus, gene transfer of TNF receptor antagonists and IL-1ra may offer a more efficient mode of delivery of disease controlling agents to the periodontal structures. Periodontal treatment through the ages has focused on the reduction of bacterial infection by mechanical removal of infectious agents (i.e., SRP). Attempts at elimination of infectious agents often do not represent a definitive therapy in periodontitis, necessitating the administration of more sophisticated biological treatment modalities. A thorough understanding of the host inflammatory response in periodontal pathogenesis presents the opportunity for exploiting new treatment strategies for periodontitis by means of host response modulation. The rationale behind this approach is to aid the host in its fight against infectious agents by supplementing the natural inherent defense mechanism or to modify its responses by changing the course of inflammatory systems. Therefore, pharmaceutical inhibition of host response pathways that mimic endogenous anti-inflammatory mechanisms may prove to be an effective strategy for treating periodontal diseases. This would require the development of polypharmaceutical approaches controlling all pathways associated with inflammation and tissue destruction. Current research has focused on the use of SDD as a treatment modality, and SDD is the only systemically used host modulatory drug approved by the United States Food and Drug Administration.
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PMID:Pathogenesis of periodontitis: role of cytokines in host response. 2097 18

In 1983, it was first reported that tetracyclines (TCs) can modulate the host response, including (but not limited to) inhibition of pathologic matrix metalloproteinase (MMP) activity, and by mechanisms unrelated to the antibacterial properties of these drugs. Soon thereafter, strategies were developed to generate non-antibacterial formulations (subantimicrobial-dose doxycycline; SDD) and compositions (chemically modified tetracyclines; CMTs) of TCs as host-modulating drugs to treat periodontal and other inflammatory diseases. This review focuses on the history and rationale for the development of: (a) SDD which led to two government-approved medications, one for periodontitis and the other for acne/rosacea and (b) CMTs, which led to the identification of the active site of the drugs responsible for MMP inhibition and to studies demonstrating evidence of efficacy of the most potent of these, CMT-3, as an anti-angiogenesis agent in patients with the cancer, Kaposi's sarcoma, and as a potential treatment for a fatal lung disease (acute respiratory distress syndrome; ARDS). In addition, this review discusses a number of clinical studies, some up to 2 years' duration, demonstrating evidence of safety and efficacy of SDD formulations in humans with oral inflammatory diseases (periodontitis, pemphigoid) as well as medical diseases, including rheumatoid arthritis, post-menopausal osteopenia, type II diabetes, cardiovascular diseases, and a rare and fatal lung disease, lymphangioleiomyomatosis.
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PMID:Non-antibacterial tetracycline formulations: clinical applications in dentistry and medicine. 2307 96