吲哚美辛糊剂治疗牙周炎效果的临床观察

<正>牙周病是牙齿缺失的主要原因。阻断牙周炎症仅占及牙槽骨吸收是治疗牙周病,保留患牙的重要环节。临床观察和病理实验发现前列腺素(PG)能够促进牙槽骨吸收,而非类固醇抗炎药物(NSAID)能够阻断列腺素合成过程,从而阻断牙槽骨吸收,动物试验也证实了这一发现。前列腺素能促进骨吸收,还能促进白细胞游走,使血管通透性增加,认为PG参与各种组织产生炎症的发病机理,而NSAID阻断了PG的合成,从而控制炎     

应用于骨科领域的缓控释药物载体材料

缓控释药物释放系统（DDS）是近年来国内外研究的热点。以各种骨修复材料为载体的药物缓控释体系是一种新型的给药方式,将DDS植人生物体内骨骼后,载体所承载的药物能够持续、稳定、高效地缓慢释放,达到修复骨缺损和药物治疗的双重目的。在治疗骨髓炎、骨肿瘤、骨结核、骨折、骨不连和人工关节置换等领域,缓控释药物载体发挥着不可低估的作用。目前在骨科治疗中使用的载体可分为非生物降解型缓控释药物载体和可生物降解型缓控释药物载体。此外,为弥补某些单一材料的缺陷,达到优势互补的目的,复合型材料逐渐成为骨科药物载体材料的研究方向之一。     

2004～2006年我院口服缓控释药物应用分析

目的:评估我院口服缓控释药物应用情况及发展趋势。方法:对我院2004～2006年口服缓控释药物的用药金额、用药频度及日均费用进行统计、分析。结果:缓控释药物用药金额、占全部用药金额的比例均呈上升趋势;循环系统用药金额、DDDs大于中枢神经系统用药,平均日限定费用中枢神经系统用药高于循环系统用药。结论:缓控释剂型能够充分发挥药物的治疗作用,减少毒副作用,具有广阔的临床前景。     

异种骨移植物BIO-OSS治疗牙周角形骨缺损58例体会

牙周炎可以导致牙周附着丧失、牙槽骨吸收和破坏。植骨术治疗是采用骨或骨替代品来修复因牙周炎造成的牙槽骨缺损,使牙槽骨恢复原有的形态,并促进牙周软硬组织的生物性结合,形成新附着。BIO-OSS是一种具有多孔结构的高纯度骨无机材料。本文的目的是评估BIO-OSS天然骨无机材料治疗深度骨吸收的疗效。     

2007—2009年我院门诊口服缓、控释药物应用分析

目的了解医院门诊口服缓、控释药物的使用情况和发展趋势。方法对2007年至2009年门诊常用口服缓控释药物使用品种、用药金额,采用金额排序和用药频度排序、日均费用进行统计分析。结果口服缓控释药物的用药金额均呈上升趋势;年用药频度硝苯地平缓释片连续3年位居首位。结论缓控释药物临床疗效明显,毒副作用小,具有广阔的临床应用前景。     

中药缓控释制剂的研究现状

缓控释制剂是很具临床意义的一类制剂,是指药物在规定释放介质中,按要求缓慢的非恒速释放。与相应的普通制剂比较,每24小时用药次数应从3～4次减少至1～2次的制剂,它是近年来制剂研究开发的热点。本文就近年来中药缓控释制剂的研究现状综述如下。1.缓控释制剂特点减少给药次数;提高病人的依从性;降低药品的不良反应;维持持久药效。是一种能提供比较平稳血药浓度的制剂,主要应用于病程较长、需长时间用药的慢性病人,特别是肿瘤患者。2.用于缓控释制剂的辅料将药物制成任何一种剂型的制剂均必须使用一定的辅料,甚至同时需要几种辅料,因此辅料…     

缓释控释浅析

缓释控释给药为当前国际上药剂学研究的重点之一,这类制剂要求平稳血药浓度达到以提高病人在疾病状态下的药效为目标。1缓释、控释给药的特点: 1．1适宜于制成缓控释制剂的药物范围广泛。首过作用强的药物中已有不少被研制成缓释及控释制     

口服缓控释剂的临床评价

目的:口服缓/控释剂与普通制剂药剂学原理、制备工艺及药效特点有所不同,加强认识有利于合理用药的开展.方法:通过收集文献资料了解我国目前常用口服缓/控释剂的运用及临床评价.结果:口服缓/控释剂多是由普通常释剂经剂型改进而来,药理作用与常释剂相同,而药效作用要优越.结论:正确认识缓/控释剂的用药特点及药物优势有利于临床合理选择药物及治疗方案.     

牙周康泰胶囊对实验性牙周炎牙槽骨的影响

目的:观察牙周康泰胶囊对实验性牙周炎牙槽骨的影响.方法:采用泼尼松龙加结扎法建立牙周炎大鼠模型,将50只wistar大鼠随机分为正常组、模型组、牙周宁对照组、牙周康泰高低剂量组,每组10 只.连续用药8周,于用药第0,1,2,4和8周各组随机取2只动物处死,拍上下颌骨软射线片,并做病理切片.观察动物的一般状况,牙槽骨吸收情况,以及牙周组织病理学变化,并测量牙槽骨高度.结果:牙周康泰高、低剂量组大鼠用药后全身症状很快得到改善,牙槽骨高度在用药4周以后均高于模型组(P＜0.05),用药第8周,牙周康泰髙剂量组高于牙周宁组(P＜0.05),组织病理学观察见牙周组织内炎症减轻,代之以新生的纤维结缔组织.结论:牙周康泰能抑制实验性牙周炎大鼠的牙槽骨吸收,促进牙周组织新生.     

细胞色素P450底物缓控释药品临床使用的安全性和有效性

目的:提高缓控释制剂临床用药的安全性和有效性.方法:从主要影响P450底物缓控释制剂代谢的因素方面进行探讨.结果:机体因素、生活因素及联合用药3个方面因素能通过P450同工酶渠道影响缓控释底物药品的吸收和代谢.结论:医师掌握影响P450缓控释底物药品吸收和代谢的因素,可提高缓控释制剂临床用药的安全性和有效性.     

Pharmacological topics of bone metabolism: a novel bisphosphonate for the treatment of periodontitis

It has been reported that the pharmacological characteristics of bisphosphonates vary depending on the side chain attached to the carbon atom of the P-C-P bond. TRK-530 is a novel synthetic bisphosphonate with an anti-oxidant methylthio-phenylthio side chain. This compound has been suggested to have both anti-inflammatory and anti-bone-resorbing effects. Such a compound could be effective for the treatment of diseases with excessive bone resorption accompanied by inflammation. We have been studying this compound as a potential therapeutic agent for periodontitis. To date, we have found that 1) TRK-530 inhibited osteoclastic bone resorption in animals and in bone organ culture, 2) both systemic and topical administration of TRK-530 prevented alveolar bone loss in animals with experimental periodontitis, 3) TRK-530 prevented prostaglandin E(2) synthesis by inhibiting the expression of cyclooxygenase (COX)-2 mRNA, and 4) TRK-530 inhibited the formation of dental calculus. The above results suggest that TRK-530 might be useful for the treatment of alveolar bone loss in periodontitis.     

Pleiotropic effects of statins on the treatment of chronic periodontitis – a systematic review

Aim

Statins are inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase and are an important group of hypolipidaemic drugs, widely used in the treatment of hypercholesterolaemia and cardiovascular disease. Some studies have shown that statins are able to modulate inflammation and alveolar bone loss.

Methods

In order to evaluate whether statins could influence periodontal treatment, improving the clinical and radiographic parameters in chronic periodontitis, a systematic review was conducted in the databases PUBMED and BIREME, searching for articles in English and Portuguese, published between the years 2004 and 2014, using the combined keywords statin, periodontal disease, periodontitis and alveolar bone. Studies regarding the treatment of chronic periodontitis in humans, blind or double-blind, retrospective cohort or randomized controlled trials that used statins topically or systemically were selected.

Results

Statins have important anti-inflammatory and immune effects, reducing levels of C-reactive protein and matrix metalloproteinases and their intermediate products, such as tumour necrosis factor-α, and are also able to inhibit the adhesion and extravasation of leukocytes, which block the co-stimulation of T cells. Statins reduce bone resorption by inhibiting osteoclast formation and lead to increased apoptosis of these cells. The effect of statins on bone formation is related to the increased gene expression of bone morphogenetic protein in osteoblasts.

Conclusion

Although we found biological mechanisms and clinical results that show lower alveolar bone loss and reduction of clinical signs of inflammation, further studies are needed to evaluate the clinical applicability of statins in the routine treatment of chronic periodontitis.     

Electrosprayed minocycline hydrochloride-loaded microsphere/SAIB hybrid depot for periodontitis treatment

Minocycline hydrochloride (MINO) has been one of the most frequently used antibiotics in the treatment of periodontitis due to its antibacterial activity and osteogenesis effects; however, high levels of MINO administered during the treatment halt the formation of new bone. Therefore, the purpose of the present study was to prepare a MINO-microsphere/sucrose acetate isobutyrate (SAIB) hybrid depot to reduce the burst release of MINO and ensure antibacterial and osteogenesis effects of MINO in the treatment of periodontitis. Uniform microspheres, approximately 5 µm size, with a slightly rough surface and different MINO loading (10, 12, and 14%) were prepared, and the microspheres were added into SAIB, after which the burst release significantly decreased from 66.18 to 2.92%, from 71.82 to 3.82%, and from 73.35 to 4.45%, respectively, and the release from all the MINO-microspheres/SAIB hybrid depots lasted for 77 days. In addition, cytotoxicity test showed that the MINO-microsphere with 12% drug loading promoted the proliferation of osteoblasts the most and was subsequently used in vivo experiments. Moreover, in the model of ligatured-induced periodontitis in SD rats, the MINO-microsphere/SAIB hybrid depot not only significantly increased the alveolar bone height and bone volume but also reduced the inflammation of the periodontal tissue. Additionally, it also inhibited the expression of the receptor activator of nuclear factor-kappa B ligand (RANKL) and promoted the expression of osteoprotegerin (OPG).. These results indicated that the MINO-microsphere/SAIB hybrid depot might be promising in the treatment of periodontitis.     

Baicalin inhibits toll-like receptor 2/4 expression and downstream signaling in rat experimental periodontitis

Periodontitis is a severe inflammatory response, leading to characteristic periodontal soft tissue destruction and alveolar bone resorption. Baicalin possesses potent anti-inflammatory activity; however, it is still unclear whether baicalin regulates toll-like receptor (TLR) 2/4 expression and downstream signaling during the process of periodontitis. In this study, the cervical area of the maxillary second molars of rats was ligated and inoculated with Porphyromonas gingivalis (P. gingivalis) for 4 weeks to induce periodontitis. Some rats with periodontitis were treated intragastrically with baicalin (50, 100 or 200 mg/kg/day) or vehicle for 4 weeks. Compared with the sham group, the levels of TLR2, TLR4 and MyD88 expression and the p38 MAPK and NF-κB activation were up-regulated in the experimental periodontitis group (EPG), accompanied by marked alveolar bone loss and severe inflammation. Treatment with 100 or 200 mg/kg/day baicalin dramatically reduced the alveolar bone loss, the levels of HMGB1, TNF-α, IL-1β, and MPO expression, and the numbers of inflammatory infiltrates in the gingival tissues. Importantly, treatment with 100 or 200 mg/kg/day baicalin mitigated the periodontitis-up-regulated TLR2, TLR4 and MyD88 expression, and the p38 MAPK and NF-κB activation. Hence, the blockage of the TLR2 and TLR4/MyD88/p38 MAPK/NF-κB signaling by baicalin may contribute to its anti-inflammatory effects in rat model of periodontitis. In conclusion, these novel findings indicate that baicalin inhibits the TLR2 and TLR4 expression and the downstream signaling and mitigates inflammatory responses and the alveolar bone loss in rat experimental periodontitis. Therefore, baicalin may be a potential therapeutic agent for treatment of periodontitis.     

A novel inhibitor of vacuolar ATPase, FR202126, prevents alveolar bone destruction in experimental periodontitis in rats

An acidic microenvironment formed by vacuolar ATPase (V-ATPase) expressed in plasma membranes of osteoclasts is thought to be indispensable for bone resorption. This study examined the efficacy of a novel V-ATPase inhibitor, FR202126, in reducing alveolar bone loss caused by experimental periodontitis in rats. FR202126 inhibited H+ transport in plasma membrane vesicles of murine osteoclasts, whereas FR202126 exerted no effect on H+ transport of mitochondrial ATPase or gastric H+,K+-ATPase, indicating that FR202126 is a specific inhibitor of V-ATPase. As expected from the mechanism, FR202126 remarkably inhibited in vitro bone resorption whatever bone resorptive factors were added. Moreover, FR202126 was also able to exert an inhibitory effect on in vivo bone resorption. Experimental periodontitis was induced by ligature wire tied around the contact between the first and second maxillary molars. Insertion of ligature wire for 7 days induced alveolar bone destruction by activating osteoclasts. Oral administration of FR202126 (u.i.d.) significantly prevented alveolar bone loss in experimental periodontitis which may offer a new approach to treatment of periodontal disease.     

Using tetracyclines to treat osteoporotic/osteopenic bone loss: From the basic science laboratory to the clinic

Periodontitis (progressive inflammatory disease characterized by alveolar bone loss, a major cause of tooth loss worldwide) is associated with both systemic osteoporosis and its milder form, osteopenia. Tetracyclines, by virtue of their non-antimicrobial pro-anabolic and anti-catabolic properties, are excellent candidate pharmaceuticals to simultaneously treat these local and systemic disorders. This paper reviews the foundational basic science and translational research which lead to a pivotal multicenter randomized clinical trial in postmenopausal women with both periodontitis and systemic (skeletal) osteopenia. This trial was designed primarily to examine whether subantimicrobial dose doxycycline (SDD) could reduce progressive alveolar (oral) bone loss associated with periodontitis and, secondarily, whether SDD could reduce systemic bone loss in the same subjects. This paper describes the efficacy and safety findings from this clinical trial and also outlines future directions using this promising and novel approach to manage both oral and systemic bone loss.     

Effects of calcium gluconate on experimental periodontitis and alveolar bone loss in rats

We examined the effects of calcium gluconate, an anti-inflammatory calcium salt, on ligature-induced experimental periodontitis and related alveolar bone loss. Calcium gluconate was orally administered daily for 10 days at 250, 125 or 62.5 mg/kg, beginning 1 day after ligation. We recorded changes in body-weight and alveolar bone loss and quantified the anti-inflammatory effects of calcium gluconate by measuring levels of myeloperoxidase (MPO), IL-1β and TNF-α. We also evaluated inducible nitric oxide synthase (iNOS) activity and malondialdehyde (MDA) concentration as a measure of antioxidant effects. Ligature placement produced a marked decrease in body-weight, increased alveolar bone loss, and led to increased MPO, IL-1β, TNF-α and MDA concentrations, as well as elevated iNOS activity, increased inflammatory cell infiltration and decreased collagen fibre content in gingival tissue. Histopathology revealed decreased alveolar bone volume, increased osteoclast cell numbers and activity, and an elevated percentage of osteclasts on the alveolar bone surface. The effects of ligature placement were significantly and dose-dependently inhibited by 10 days of daily oral treatment with 250 and 125 mg/kg of calcium gluconate. The results suggest that 10 days daily oral treatment with calcium gluconate effectively inhibits ligature placement-induced periodontitis and related alveolar bone loss via antioxidant effects.     

黄芪注射液治疗大鼠牙周炎作用研究

目的:研究黄芪注射液对大鼠牙周炎的治疗作用。方法:采用牙龈划割剥离加高糖饲料和高糖饮水喂养的方法复制大鼠牙周炎模型,以血液生化指标和临床观察指标考察黄芪注射液8.0g·kg-1剂量下连续给药10d的治疗作用。结果:黄芪注射液能显著降低牙周炎大鼠的血清白细胞、中性粒细胞等指标含量,对红细胞、血小板、血红蛋白无降低作用;同时能显著降低牙周炎大鼠的龈沟出血指数、菌斑指数、牙槽骨吸收值、牙齿松动度,而对探针深度、丧失值、牙周骨支持率等指标无明显改善。结论:黄芪注射液对大鼠牙周炎有一定的治疗作用。     

Histone deacetylase inhibitors as suppressors of bone destruction in inflammatory diseases

Objectives Despite progress in developing many new anti‐inflammatory treatments in the last decade, there has been little progress in finding treatments for bone loss associated with inflammatory diseases, such as rheumatoid arthritis and periodontitis. For instance, treatment of rheumatic diseases with anti‐tumour necrosis factor‐alpha agents has been largely successful in reducing inflammation, but there have been varying reports regarding its effectiveness at inhibiting bone loss. In addition, there is often a delay in finding the appropriate anti‐inflammatory therapy for individual patients, and some therapies, such as disease modifying drugs, take time to have an effect. In order to protect the bone, adjunct therapies targeting bone resorption are being developed. This review focuses on new treatments based on using histone deacetylase inhibitors (HDACi) to suppress bone loss in these chronic inflammatory diseases. Key findings A number of selected HDACi have been shown to suppress bone resorption by osteoclasts in vitro and in animal models of chronic inflammatory diseases. Recent reports indicate that these small molecules, which can be administered orally, could protect the bone and might be used in combination with current anti‐inflammatory treatments. Summary HDACi do have potential to suppress bone destruction in chronic inflammatory diseases including periodontitis and rheumatoid arthritis.     

Local Application of Pyrophosphorylated Simvastatin Prevents Experimental Periodontitis

Purpose

Simvastatin (SIM), a HMG-CoA reductase inhibitor widely prescribed for hypercholesterolemia, has been reported to ameliorate inflammation and promote osteogenesis. Its clinical applications on these potential secondary indications, however, have been hampered by its lack of osteotropicity and poor water solubility. To address this challenge, we propose to design and evaluate the therapeutic efficacy of a novel simvastatin prodrug with better water solubility and bone affinity.

Method

The prodrug (SIM-PPi) was synthesized by directly conjugating a SIM trimer to a pyrophosphate (PPi). It was characterized and evaluated in vitro for its water solubility, osteotropicity, toxicity, anti-inflammatory and osteoinductive properties. It was then tested for anti-inflammatory and osteoinductive properties in vivo by three weekly injections into gingiva of a ligature-induced experimental periodontitis rat model.

Results

In vitro studies showed that SIM-PPi has greatly improved water-solubility of SIM and shows strong binding to hydroxyapatite (HA). In macrophage culture, SIM-PPi inhibited LPS-induced pro-inflammatory cytokines (IL-1β, IL-6). In osteoblast culture, it was found to significantly increase alkaline phosphatase (ALP) activity with accelerated mineral deposition, confirming the osteogenic potential of SIM-PPi. When tested in vivo on an experimental periodontal bone-loss model, SIM-PPi exhibited a superior prophylactic effect compared to dose equivalent SIM in reducing inflammatory cells and in preserving alveolar bone structure, as shown in the histological and micro-CT data.

Conclusion

SIM-PPi may have the potential to be further developed for better clinical management of bone loss associated with periodontitis.