Subantimicrobial-dose doxycycline and cytokine-chemokine levels in gingival crevicular fluid

Background: The present randomized, double‐masked, placebo‐controlled, parallel‐arm study examines the impact of adjunctive subantimicrobial‐dose doxycycline (SDD) on the local inflammatory response through cytokine and chemokine levels in gingival crevicular fluid (GCF) samples from patients with chronic periodontitis. Methods: Forty‐six patients with chronic periodontitis received scaling and root planing with or without adjunctive SDD. GCF samples were collected and clinical parameters including probing depth, clinical attachment level, gingival index, and plaque index were recorded every 3 months for 12 months. GCF tumor necrosis factor‐α, interleukin (IL)‐6, IL‐4, IL‐10, IL‐13, IL‐17, macrophage inhibitory protein 1α, macrophage inhibitory protein 1β, monocyte chemoattractant protein 1, and regulated on activated normal T‐cell expressed and secreted protein levels were determined by xMAP multiplex immunoassay. Results: Significant improvements were observed in all clinical parameters in both groups over 12 months (P <0.0125), whereas the SDD group showed significantly better reduction in gingival index, probing depth, and gain in clinical attachment compared to the placebo group (P <0.05). Decrease in IL‐6 in the SDD group was significantly higher compared to the placebo group at 6 and 9 months in deep pockets (P <0.05), whereas tumor necrosis factor‐α was significantly reduced in moderately deep pockets (P <0.05). SDD resulted in a stable IL‐4 and IL‐10 response while reducing the monocyte chemoattractant protein 1 levels at 3 months (P <0.05). Conclusions: These results show that SDD, as an adjunct to non‐surgical periodontal therapy, stabilizes the inflammatory response by promoting the suppression of proinflammatory cytokines and increasing the anti‐inflammatory cytokines. The chemokine activity would account for the regulation of the inflammatory response to SDD therapy.     

Subantimicrobial dose doxycycline as adjunctive treatment for periodontitis. A review

BACKGROUND: Subantimicrobial dose doxycycline (SDD--20 mg doxycycline twice daily) is indicated as an adjunctive treatment for periodontitis. Doxycycline downregulates the activity of matrix metalloproteinases (MMPs), key destructive enzymes in periodontal disease. Current understanding of periodontal pathogenesis suggests that MMPs play a major role in the destruction of periodontal tissues, leading to the clinical signs of periodontitis. Research supports that downregulation of MMPs by SDD confers benefit to patients with periodontitis. METHOD: We review the clinical, microbiological and safety data relating to the use of SDD in patients with periodontitis, and consider the historical events that led to the development of adjunctive SDD as a treatment for periodontitis. RESULTS: Studies have shown that SDD, when prescribed as an adjunct to scaling and root planing (SRP), results in statistically and clinically significant gains in clinical attachment levels and reductions in probing depths over and above those that are achieved by SRP alone. SRP must be thorough and performed to the highest standard to maximise the benefits of adjunctive SDD. SDD does not result in antibacterial effects, or lead to the development of resistant strains or the acquisition of multiantibiotic resistance. The frequency of adverse events is low, and does not differ significantly from placebo. CONCLUSIONS: Adjunctive SDD confers clinical benefit to patients with periodontitis. A comprehensive treatment strategy is suggested, involving patient education and motivation, reduction of the bacterial burden by SRP, host response modulation with SDD, and periodontal risk factor modification.     

PTEN基因联合多西环素抑制黏液表皮样癌细胞系端粒酶活性的研究

目的探讨外源性PTEN抑癌基因联合多西环素对人黏液表皮样癌细胞系端粒酶活性的影响。方法用脂质体将野生型PTEN基因导入黏液表皮样癌细胞系,再用不同质量浓度的多西环素处理细胞,采用MTT比色法测定细胞存活,用端粒酶重复扩增法-酶联免疫吸附（TRAP-ELISA）测定细胞端粒酶活性。结果与对照细胞比较,野生型PTEN基因明显增加癌细胞对多西环素的敏感性,增敏比为1.65～4.75倍。PTEN基因转染或多西环素诱导癌细胞端粒酶活性明显下降（P＜0.05）,二者联合应用对癌细胞端粒酶活性抑制更为显著（P＜0.01）。结论PTEN抑癌基因联合多西环素对人黏液表皮样癌细胞系端粒酶活性具有显著的协同抑制效应。     

复方甘草酸苷联合西药治疗慢性布氏杆菌病

目的探讨复方甘草酸苷、左氧氟沙星、多西环素三药联合应用治疗慢性布氏杆菌病的临床效果。方法选取我院2010年1月—2013年1月间收治的慢性布氏杆菌病患者140例,随机分为观察组与对照组,观察组患者给予复方甘草酸苷+左氧氟沙星+多西环素口服治疗,对照组给予左氧氟沙星片+多西环素片口服治疗,2组患者均以治疗3周为1疗程,间隔1周后,继续第2疗程,对比治疗2个疗程后2组临床疗效及不良反应发生情况。结果观察组治疗后痊愈率为98.6%,对照组痊愈率为70.0%,组间比较(P0.05);观察组发生不良反应8例(11.4%),对照组发生不良反应26例(37.1%),组间比较(P0.05)。结论复方甘草酸苷、左氧氟沙星、多西环素三药联合应用治疗慢性布氏杆菌病疗效确切,不良反应发生率低,是治疗慢性布氏杆菌病的有效治疗方案。     

基质金属蛋白酶及抑制剂在心肌梗死后心室重构中的作用

目的　研究大鼠心肌梗死后外源性基质金属蛋白酶抑制剂 (多西环素 ,Doxycycline)在心室重构中的作用。方法　 70只SD大鼠随机分为对照组 (10只 )、手术对照组 (9只 )、心肌梗死后 1天组 (10只 )、心肌梗死后 1周组 (10只 )、心肌梗死后 2周组 (8只 )、心肌梗死后 4周组 (7只 )、治疗 2周组 (8只 )和治疗 4周组 (8只 ) ,采用免疫组织化学、酶谱法、免疫印迹 (WesternBlotting)、逆转录 聚合酶链反应 (RT PCR)和AcusonSequoia 5 12超声心动图仪分别测定胶原含量 ,Ⅰ Ⅲ胶原比例、基质金属蛋白酶 2 ,9(MMP 2 ,9)蛋白和mRNA的变化规律及心功能。结果　多西环素治疗后 ,胶原含量明显减少 ,Ⅰ Ⅲ胶原比例下降得以改善 (P <0 .0 5 ) ,MMP 2 ,9蛋白和mRNA在心肌梗死后活性减少 ,基质金属蛋白酶组织抑制剂 1蛋白含量和mRNA转录无明显变化 ,治疗组心功能在术后 4周得以改善。结论　多西环素治疗后MMP 2 ,9的mRNA转录减少 ,MMP 2 ,9活性降低 ,胶原含量减少 ,Ⅰ Ⅲ胶原比例恢复 ,这些影响可能是其改善心肌梗死后心室重构的机制之一。     

多西环素对哮喘大鼠血管内皮生长因子、基质金属蛋白酶9的作用及血管重塑的影响

目的 观察多西环素对哮喘大鼠血管内皮生长因子(vascular endothelial growth factor,VEGF)、基质金属蛋白酶9(matrix metalloproteinases-9,MMP-9)表达的影响.探讨多西环素对哮喘气道重塑、血管重塑的作用.方法 33只雄性SD大鼠随机分为对照组、哮喘组、多西环素组各11只.将大鼠以1％戊巴比妥钠麻醉,取材.收集支气管肺泡灌洗液(bronchoalveolar lavage fluid,BLAF),计数细胞总数、中性粒细胞、淋巴细胞及嗜酸性粒细胞;部分肺组织行病理切片,HE染色;免疫组织化学法检测各组大鼠肺组织中VEGF和MMP-9的表达变化,并应用图像分析软件技术测量VEGF和MMP-9的相对表达强度;ELISA法检测血清中VEGF的含量;应用计算机图像分析技术测定气道壁厚度及血管密度.结果 哮喘组的细胞总数和嗜酸性粒细胞高于对照组,多西环素组明显低于哮喘组,但仍高于对照组(均P＜0.01);哮喘组大鼠肺组织和血清中MMP-9及VEGF的平均光密度值高于对照组,多西环素组明显低于哮喘组,但仍高于对照组(均P＜0.01);哮喘组大鼠血清中的VEGF含量高于对照组,多西环素组低于哮喘组,但仍高于对照组(均P＜0.01).哮喘组大鼠的气道壁厚度与血管密度均高于对照组,多西环素组则明显低于哮喘组,但仍高于对照组(均P＜0.01).结论 MMP-9、VEGF对哮喘血管重塑有重要作用,多西环素具有减轻气道炎症和气道重塑的作用.     

Antibiotic susceptibility among Staphylococcus epidermidis isolated from prosthetic joint infections,with focus on doxycycline

In recent years, coagulase‐negative staphylococci such as Staphylococcus epidermidis have gained importance as nosocomial pathogens, especially in immunocompromised patients and prosthetic joint infections (PJIs). These infections are often long lasting and difficult to treat due to the production of bacterial biofilm and the transformation of the bacteria into a stationary growth phase. Rifampicin is able to penetrate the biofilm, but to reduce the risk of development of rifampicin resistance it should be used in combination with an additional antibiotic. In this study we used Etest to investigate the antimicrobial susceptibility of 134 clinical isolates of S. epidermidis obtained from PJIs to six oral antibiotics: doxycycline, rifampicin, linezolid, fusidic acid, clindamycin, and ciprofloxacin. We also performed synergy testing on doxycycline in combination with each of the remaining antibiotics. Ninety‐three (69%) of the 134 isolates were susceptible to doxycycline, 94/134 (70%) to rifampicin, 56/134 (42%) to clindamycin, 25/134 (19%) to ciprofloxacin, 81/134 (60%) to fusidic acid, and 100% to linezolid. Thirty‐two (80%) of the 40 isolates not fully susceptible to rifampicin were susceptible to doxycycline. Doxycycline in combination with each of the other investigated antibiotics exerted an additive effect on nearly half of the isolates, with the exception of clindamycin, which displayed an even higher percentage of additive effect (69%). To conclude, as the majority of the S. epidermidis isolates were susceptible to doxycycline, this antimicrobial agent may provide a potential alternative for combination therapy together with rifampicin.     

Experimental doxycycline overdose in rats causes cardiomyopathy

All reports of doxycycline‐induced cardiomyopathy to date have been limited to accidental oral poisoning in calves. Therefore, the current study investigated the cardiomyotoxic effect of experimental doxycycline overdose in rats as a toxicity model which could be monitored using histopathological and biochemical assays. A total of 38‐week‐old male Wistar rats were divided into three groups consisting of 10 each. The first group was an untreated control group (D₀), and the second group (D₅) received doxycycline hyclate 25 mg/kg intragastrically twice daily (8 AM and 8 PM), which is 5‐fold higher than the standard dose. The third group (D₁₀) received 50 mg/kg intragastrically twice daily (8 AM and 8 PM), which is 10‐fold higher than the standard dose. The dose continued for 10 consecutive days and revealed that the doxycycline toxicity was dose dependent. Mortality was recorded in the D₁₀ group only (30%). The D₅ rats exhibited minimal skeletal muscle injury and slight but significant increases in the skeletal muscle damage indicators creatine kinase (CK) and aspartate aminotransferase (AST) compared to controls. The cardiac muscle of the D₅ rats was histologically normal, and the D₅ rats also exhibited normal levels of troponin I (cTnI), an indicator of cardiac muscle damage. In contrast, the D₁₀ rats displayed cardiomyopathy, as well as significant increases in the muscle enzymes alanine aminotransferase (ALT), AST and CK and the cardiac damage indicator cTnI compared to control and D₅ groups. Pulmonary lesions were observed in the D₁₀ rats, primarily cardiac lesion‐related alveolar heart failure cells. Thus the present study is the first to demonstrate that oral doxycycline poisoning (10 times the therapeutic dose)‐induced cardiomyopathy is not limited to calves and could occur without any predisposing factors.