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Chemically modified tetracyclines: Novel therapeutic agents in the management of chronic periodontitis

机译:化学修饰的四环素:治疗慢性牙周炎的新型治疗剂

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摘要

Chronic periodontitis is a complex infection initiated by gram-negative bacteria which destroy the supporting structures of the tooth. Recently, it has been recognized that it is the host response to bacterial infection which causes greater destruction of the connective tissue elements, periodontal ligament and alveolar bone in periodontitis. This has led to the development of various host modulating approaches to target cells and their destructive mediators involved in tissue degradation. Chemically modified tetracyclines (CMTs) are derivatives of tetracycline group of drugs which lack antimicrobial action but have potent host modulating affects. They inhibit pathologically elevated matrix metal loproteinases, pro-inflammtory cytokines and other destructive mediators. Bone resorption is also suppressed due to their combined anti-proteinase and apoptotic affects on osteoblasts and osteoclasts, respectively. Development of resistant bacteria and gastrointestinal toxicity seen with parent tetracyclines is not produced by CMTs. Hence, CMTs are viewed as potential therapeutic agents in the management of chronic diseases like periodontitis that involve destruction of connective tissue and bone.
机译:慢性牙周炎是由革兰氏阴性细菌引发的复杂感染,这种细菌会破坏牙齿的支撑结构。最近,已经认识到,对细菌感染的宿主反应导致牙周炎中结缔组织成分,牙周韧带和牙槽骨的更大破坏。这导致针对靶细胞及其参与组织降解的破坏性介质的多种宿主调节方法的发展。化学修饰的四环素(CMT)是四环素类药物的衍生物,缺乏抗菌作用,但具有有效的宿主调节作用。它们抑制病理上升高的基质金属蛋白酶,促炎性细胞因子和其他破坏性介质。由于它们分别结合抗蛋白酶和凋亡对成骨细胞和破骨细胞的影响,因此也抑制了骨吸收。 CMT不会产生亲代四环素所产生的抗药性细菌和胃肠道毒性。因此,CMT被视为治疗诸如牙周炎之类的慢性疾病的潜在治疗剂,这些疾病涉及结缔组织和骨骼的破坏。

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