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.     

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.     

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.     

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。     

多西环素与平阳霉素治疗儿童大囊型淋巴管畸形的比较研究

目的比较注射用盐酸多西环素与注射用盐酸平阳霉素治疗儿童大囊型淋巴管畸形的临床疗效。方法选取2012年1月—2017年6月天津市儿童医院治疗的60例大囊型淋巴管畸形的患儿作为研究对象,将患儿根据治疗药物的不同分为对照组和治疗组,每组各30例。对照组在DSA透视下经皮注射注射用盐酸平阳霉素8 mg、碘海醇注射液4 mL与生理盐水4 mL组成的混合液,完成后摄片,平阳霉素用量为从病变中吸出体积的1/3～1/2,但总量不超过8 mg。治疗组在DSA透视下经皮注射注射用盐酸多西环素0.1 g、碘海醇注射液2.5 mL与生理盐水2.5mL组成的混合液,完成后摄片,多西环素用量为从病变中吸出体积的1/3～1/2,但总量不超过250 mg。所有患儿均于治疗后4周随访,4周后若患儿未达治愈标准可重复进行,3～5次为1个疗程,术后随访18个月。观察两组患者的临床疗效,比较两组瘤体体积变化情况和不良反应情况。结果治疗后,对照组和治疗组总有效率分别为80.0%、96.7%,两组比较差异有统计学意义(P0.05)。治疗后,两组病变瘤体体积均显著减少,同组治疗前后比较差异具有统计学意义(P0.05);治疗后,治疗组病变瘤体体积显著小于对照组,两组比较差异具有统计学意义(P0.05)。治疗期间,对照组和治疗组的不良反应发生率分别为33.3%、10.00%,两组比较差异具有统计学意义(P0.05)。结论多西环素治疗儿童大囊型淋巴管畸形的疗效优于平阳霉素,可以显著减少病变瘤体体积,安全性高,具有一定的临床推广应用价值。     

Susceptibility of clinical Moraxella catarrhalis isolates in British Columbia to six empirically prescribed antibiotic agents

BACKGROUND:

Moraxella catarrhalis is a commensal organism of the respiratory tract that has emerged as an important pathogen for a variety of upper and lower respiratory tract infections including otitis media and acute exacerbations of chronic bronchitis. Susceptibility testing of M catarrhalis is not routinely performed in most diagnostic laboratories; rather, a comment predicting susceptibility based on the literature is attached to the report. The most recent Canadian report on M catarrhalis antimicrobial susceptibility was published in 2003; therefore, a new study at this time was of interest and importance.

OBJECTIVE:

To determine the susceptibility of M catarrhalis isolates from British Columbia to amoxicillin-clavulanate, doxycycline, clarithromycin, cefuroxime, levofloxacin and trimethoprimsulfamethoxazole.

METHODS:

A total of 117 clinical M catarrhalis isolates were isolated and tested from five Interior hospitals and two private laboratory centres in British Columbia between January and December 2012. Antibiotic susceptibility of M catarrhalis isolates was characterized using the Etest (E-strip; bioMérieux, USA) according to Clinical Laboratory Standards Institute guidelines.

RESULTS:

All isolates were sensitive to amoxicillin-clavulanate, doxycycline, clarithromycin, levofloxacin and trimethoprimsulfamethoxazole. One isolate was intermediately resistant to cefuroxime, representing a 99.15% sensitivity rate to the cephem agent. Cefuroxime minimum inhibitory concentrations (MICs) inhibiting 50% and 90% of organisms (MIC50 and MIC90) were highest among the antibiotics tested, and the MIC90 (3 μg/mL) of cefuroxime reached the Clinical Laboratory Standards Institute breakpoint of susceptibility.

DISCUSSION:

The antibiotic susceptibility of M catarrhalis isolates evaluated in the present study largely confirms the findings of previous surveillance studies performed in Canada. Cefuroxime MICs are in the high end of the sensitive range and the MIC50 and MIC90 observed in the present study are the highest ever reported in Canada.

CONCLUSION:

Although cefuroxime MICs in M catarrhalis are high, all agents tested showed antimicrobial activity, supporting their continued therapeutic and empirical use.