A retrospective study of the therapeutic efficacy of doxycycline on concurrent canine ehrlichiosis and babesiosis in a veterinary hospital population

Doxycycline has a well known broad spectrum activity against bacteria and rickettsia, as well as Ehrlichia spp. However, the use of doxycycline for the treatment of concurrent ehrlichiosis and babesiosis has rarely been evaluated, especially in veterinary hospital populations. A retrospective study of 70 canine ehrlichiosis and 12 canine babesiosis concurrent infections from Out Patient Department patients at Chulalongkorn Small Animal Teaching Hospital, admitted during 2001–2003, were studied. The results showed a complete curative effect of doxycycline on both canine ehrlichiosis and canine babesiosis concurrent infections. The red blood cell indices after treatment were significantly higher in canine ehrlichiosis (P < 0.05). The platelet cell counts after treatment were significantly higher in concurrent canine ehrlichiosis and babesiosis infections (P < 0.05). Doxycycline can be recommended as the drug of choice for both canine ehrlichiosis and canine babesiosis and concurrent infections of both conditions in veterinary hospitals.     

强力霉素影响基质金属蛋白酶活性和血管重构的实验研究

目的：观察强力霉素对损伤动脉组织中基质金属蛋白酶（MMP）活性的抑制作用，并探讨强力霉素对血管平滑肌细胞增殖、动脉内膜增生、管腔重构的影响。方法:球囊导管扩张动脉的方法建立大鼠颈总动脉损伤模型。治疗组用强力霉素30 mg·kg^-1·d^-1干预。明胶酶谱法测定损伤动脉组织中MMPs的活性。用HE染色、VVG染色、免疫组化标记α-actin和增殖细胞核抗原的方法观察损伤动脉内膜厚度、管腔重构及平滑肌细胞增殖的情况。结果:①强力霉素治疗组MMP-9活性在术后24 h、3 d分别比对照组低26.3％、34.5％（P<0.01）；MMP-2活性在术后7 d比对照组低40.0％（P<0.01）。②强力霉素治疗使术后7 d内膜平滑肌细胞增殖率（43.23％±1.06％）显著低于对照组（62.76％±1.02％）（P<0.01）；使术后14 d、28 d新生内膜厚度比对照组分别少32.0％、38.8％（P<0.01），而管腔面积比对照组多58.0％、90.4％（P<0.01） 。结论：强力霉素可以显著降低血管损伤后MMPs活性，抑制内膜平滑肌细胞的增殖、新生内膜增生以及管腔重构，提示它可能具有防治PTCA术后再狭窄的作用。     

The tetracycline analogs minocycline and doxycycline inhibit angiogenesis in vitro by a non-metalloproteinase-dependent mechanism

The tetracycline analogs minocycline and doxycycline are inhibitors of metalloproteinases (MMPs) and have been shown to inhibit angiogenesis in vivo. To further study the mechanism of action of these compounds we tested them in an in vitro model of angiogenesis: aortic sprouting in fibrin gels. Angiogenesis was quantitated in this system by a unique application of planar morphometry. Both compounds were found to potently inhibit angiogenesis in this model. To further characterize the activity of these compounds against MMPs, we determined the IC₅₀s of both compounds against representatives of three classes of metalloproteinases: fibroblast collagenase, stromelysin, and gelatinase A. Doxycycline was found to inhibit collagenase, gelatinase A and stromelysin with IC₅₀s of 452 M, 56 M and 32 M, respectively. Minocycline was found to inhibit only stromelysin in the micromolar range with an IC₅₀ of 290 M. Since these results suggest that these compounds may not have been inhibiting in vitro angiogenesis by an MMP-dependent mechanism, we decided to test the effects of the potent MMP inhibitor BB-94. This compound failed to inhibit aortic sprouting in fibrin gels, thus strongly suggesting that both doxycycline and minocycline act by an MMP-independent mechanism. These results have implications for the mechanism of action of tetracycline analogs, particularly where they are being considered for the treatment of disorders of extracellular matrix degradation including periodontal disease, arthritis, and tumor angiogenesis.     

盐酸多西环素片有关物质测定方法的讨论

目的:讨论中国药典盐酸多西环素片有关物质测定方法的合理性.方法:以一批盐酸多西环素片为例,通过改变色谱条件,分别测定盐酸多西环素片中有关物质的含量,比较结果的异同,并分析原因.结果:同一批样品,在中国药典允许的调整范围内改变色谱条件,可以得出截然不同的结论,通过HPLC-PDA分析,发现是由于样品中有一未知杂质,按现行中国药典方法未得到分离,而依据现行判定方法造成误判所致.结论:中国药典盐酸多西环素片有关物质测定方法有待完善.     

盐酸多西环素羧甲基壳聚糖微球的体外释放研究

目的:探讨各因素对盐酸多西环素羧甲基壳聚糖微球体外释放度的影响。方法:采用乳化-交联固化法制备盐酸多西环素羧甲基壳聚糖微球(doxycycline hydrochloride-carboxymethyl chitosan-microspheres,DXY-CMCTS-MS),采用动态透析法测定体外释药性能,用紫外分光法测定盐酸多西环素浓度,绘制其释放曲线。结果:释放介质pH越大,交联剂量越大,固化时间越长,药物/载体比例越小,药物的释放则越慢。结论:该制剂制备工艺切实可行,所得DXY-CMCTS-MS具有明显的缓释效果。     

米诺环素对224株肠球菌的体外抗菌活性研究

目的:考察米诺环素对224株肠球菌的体外抗菌活性.方法:用二倍琼脂稀释法对224株肠球菌进行体外抗菌实验,并与多西环素、替考拉宁、万古霉素等进行抗菌效果对比.结果:米诺环素对169株粪肠球菌和51株屎肠球菌的MIC90分别为4和2μg·ml-1,而多西环素对169株粪肠球菌和51株屎肠球菌的MIC90则分别为4和4μg·ml-1.结论:米诺环素对肠球菌的抗菌效果与多西环素相似.     

戴力新合并多西环素治疗慢性前列腺炎伴状态焦虑

目的:研究戴力新合并多西环素对慢性前列腺炎伴状态焦虑的临床疗效.方法:将90例慢性前列腺炎伴状态焦虑的患者随机分为2组,一组采用多西环素加戴力新治疗,另一组采用多西环素加安慰剂治疗,疗程4周.结果:多西环素加戴力新组和多西环素加安慰剂组治疗慢性前列腺的总有效率分别为55.8%和27.3%(二者比较:P＜0.01),治疗状态焦虑的总有效率分别为79.1%、29.5%(二者比较:P＜0.01).结论:对慢性前列腺炎伴状态焦虑患者,给予多西环素治疗慢性前列腺炎的同时,给予戴力新抗焦虑治疗,能取得良好的综合疗效.     

Pin1在皮肤组织中的表达以及可诱导转基因小鼠模型的建立

目的 观察Pin1在皮肤中的表达情况，构建Pin1在皮肤中可诱导表达的转基因小鼠模型。方法 将小鼠Pin1基因克隆到改造过的可与Myc标签蛋白融合的pTRE2载体中，并将线性化的DNA通过显微注射的方式构建TRE-Pin1小鼠。结果 我们成功获得TRE-Pin1转基因首建鼠，该小鼠与上皮特异的K14-rtTA转基因小鼠配繁，获得Pin1在皮肤上皮特异性的可诱导表达的双转基因小鼠；我们通过将多西霉素（又名强力霉素， Doxycycline）加入饮水的方式诱导Pin1基因的表达，并通过Western blot，免疫组织化学等方式证明了Pin1蛋白在皮肤上皮中能特异性地过表达。我们还发现内源的Pin1在皮肤中主要表达于上皮细胞。结论 我们成功地构建Pin1在皮肤中可诱导表达的转基因小鼠模型，为后续研究Pin1在皮肤中的功能奠定基础。