PTEN基因联合多西环素对黏液表皮样癌细胞增殖的影响

目的：探讨PTEN抑癌基因联合多西环素（Dox）对黏液表皮样癌细胞系增殖的影响。方法：用脂质体将野生型PTEN基因导人人黏液表皮样癌细胞系,再用不同浓度的多西环素处理细胞,采用MTT比色法测定细胞存活,应用HE染色判定细胞形态,用流式细胞仪检测细胞周期,用免疫组化染色检测细胞PCNA和EGFR蛋白表达。结果：PTEN基因转染联合Dox组癌细胞增殖抑制显著,细胞出现空泡变性和凋亡,多数癌细胞阻滞于G1期,癌细胞中PCNA和EGFR蛋白的表达显著减弱,比PTEN基因转染或Dox单用作用更强。结论：PTEN抑癌基因联合多西环素对黏液表皮样癌细胞系增殖具有显著的协同抑制效应。     

A multi-centre surgical trial of intravenous doxycycline ('Vibravenous') in The Netherlands

Summary

One hundred and thirteen surgical patients were included in a trial of the use of doxycycline. The majority of the patients were initially started on intravenous therapy and then switched to oral medication when their condition permitted. The patients were categorized into 5 groups as follows: appendicitis 32, peritonitis 29, infections of the biliary tract 10, other infective processes 9, and prophylactic therapy 33. The efficacy was excellent and the majority of the patients had a very good (excellent) and good therapeutic response. The mean temperature in most of the groups fell significantly by the fourth or fifth day of therapy. Side-effects were few (4.4 %) and usually self-limiting.     

Matrix metalloproteinases: Targets for doxycycline to prevent the vascular alterations of hypertension

Hypertension is associated with well known structural and functional alterations in both resistance and conduit arteries, which may be the result from long-lasting high blood pressure and may also be the cause of maintained hypertension and its complications. Therefore, in addition to lowering blood pressure, therapeutic strategies targeting the structural and functional modifications found in hypertensive patients may prevent the cardiovascular events and decrease the death rates associated with hypertension. Mounting evidence indicates that many vascular alterations associated with sustained hypertension are due to imbalanced matrix metalloproteinases (MMPs), a family of zinc-endopeptidases that degrade not only proteins of extracellular matrix (ECM) but several other substrates. Recent observations showed that abnormal MMP activity is a feature of the pathogenesis of hypertension and other diseases, thus justifying the development of drugs aiming at MMP downregulation. This review focuses on the extracellular actions of MMPs in hypertension-induced chronic vascular alterations. We then discuss the effects of MMP inhibitors, especially doxycycline, on the vascular changes associated with hypertension. There is now strong evidence that MMP inhibition with doxycycline (and maybe other MMP inhibitors) may attenuate the functional and structural alterations associated with hypertension, including increases in arterial stiffness. These beneficial effects may be, at least in part, independent of their antihypertensive effects.     

pTet-on骨骺干细胞株的建立和pTRE-甲状旁腺相关蛋白(1-36)反应质粒的构建

目的 建立pTet-on骨骺干细胞株,克隆甲状旁腺相关蛋白[PTHrP(1-36)]基因并构建反应质粒pTRE-PTHHrP(1-36).方法 用脂质体介导的基因转染技术将pTet-on质粒转染于永生化骨骺干细胞,G418筛选得到稳定克隆,再瞬时转染pTRE-2Hyg-Luc质粒并筛选出高水平诱导、低背景表达的永生化骨骺干细胞系.以RT-PCR方法获得带有酶切位点PTHrP(1-36)基因片段,与载体pTRE-2Hyg均双酶切后连接,转化扩增后对重组质粒进行提取和酶切、测序鉴定.结果 筛选到1株诱导后荧光素酶的表达活性增加50倍的骨骺干细胞系;经酶切图谱分析和DNA序列测定证实目的基因已经插入重组质粒.结论 筛选得到的永生化骨骺干细胞株受强力霉素诱导后能够低背景、高水平表达;成功克隆PTHrP(1-36)基因并构建了反应质粒pTRE-PTHrP(1-36),为进一步精确调控PTHrP(1-36)基因的表达奠定了基础.     

广谱基质金属蛋白酶抑制剂对高血压性脑卒中影响的实验研究

目的研究广谱基质金属蛋白酶抑制剂多西环素对卒中易感型自发性高血压大鼠(SHR-SP)脑血管系统基质金属蛋白酶的作用,探讨多西环素对脑卒中的发病率及病死率的影响。方法80只7周龄雄性SHR-SP大鼠随机分为药物干预组和对照组,每组再随机分为两个亚组,一个亚组用于观察脑卒中体征的发生情况,并比较两组脑卒中的发病率和病死率;采用明胶酶谱分析存活大鼠脑组织MMP-2和MMP-9活性,另一亚组进行血流动力学分析,且经氯化三苯基四唑氮(TTC)染色后用于分析脑卒中病灶的范围、数量和体积。结果(1)血流动力学分析显示多西环素组左心室 dp/dtmax、-dp/dtmin值较对照组增大[(15410.1±1679.2比对照组13684.1±1882.2和-10976.8±1372.6比对照组-9429.6±1840.9)mmHg/s,P<0.05]。(2)脑组织明胶酶谱分析显示多西环素组脑组织MMP-2活性较对照组降低。(3)大脑TTC染色结果显示多西环素组脑卒中病灶体积与对照组比较无显著性差异[(205.4±244.4比对照组167.1±274.3)mm3,P>0.05]。而多西环素组脑出血体积有大于对照组的趋势,但无统计学差异[(19.6±42.1比对照组3.4±5.0)mm3,P=0.176]。(4)多西环素组与对照组比较,脑卒中的病灶率(χ2=0.042)与病死率(χ2=0.135)无显著性差异(P>0.05)。结论多西环素可以抑制SHR-SP大脑中MMP-2活性,但在血压未控制时不能有效降低SHR-SP脑卒中发病率及脑卒中病灶体积。     

用利福平和强力霉素治疗急性期和亚急性期布鲁氏菌病42例疗效报告

本文报告用利福平和强力霉素治疗急性期和亚急性期布鲁氏菌病42例,治愈41例,治愈率97.62％,基本治愈1例,占2.38％。经对全部治愈病人在6个月、12个月时两次随访结果,无一例复发。与其他治疗方法疗效对比,证明该法有用药方便,疗程短,副作用小,疗效高,复发率低等优点。     

盐酸多西环素微球温敏凝胶剂的表征及对大鼠牙周炎的药效评价

目的：评价盐酸多西环素（ Doxycycline Hydrochloride,DXY）微球温敏凝胶剂（ DXY-MS-GEL）的体外特性和对大鼠实验性牙周炎的治疗效果。方法：通过胶凝化温度和体外释药曲线评价DXY-MS-GEL的体外特性。采用内毒素隔日注射法建立Wistar大鼠牙周炎动物模型。将大鼠随机分为3组,空白对照组不予处理,实验组给以自制的DXY微球温敏性凝胶,阳性对照组给以盐酸米诺环素（派丽奥）软膏,隔日注射1次×5。末次给药后1 d测定牙龈出血指数、牙周指数、牙周探诊深度、菌斑指数、牙槽骨丧失量,观察组织病理学切片。结果：DXY-MS-GEL在室温下为自由流动的液体,37℃的平均凝胶时间为1.1±0.3 min,可持续释药24 h,体外释药曲线符合Higuchi方程,R2＝0.9948。与空白对照组相比,实验组和阳性对照组各观测指标差异均具有统计学意义（ P＜0.05）,而实验组和阳性对照组之间对比差异无统计学意义。结论：DXY微球温敏性凝胶对牙周炎的局部治疗效果显著。     

Doxycycline use in patients with lymphangioleiomyomatosis: biomarkers and pulmonary function response ,

OBJECTIVE:

To assess blockade of matrix metalloproteinase (MMP)-2 and MMP-9, as well as the variation in FEV₁, in patients with lymphangioleiomyomatosis (LAM) treated with doxycycline (a known MMP inhibitor) for 12 months.

METHODS:

An open-label, single-arm, interventional clinical trial in which LAM patients received doxycycline (100 mg/day) for 12 months. Patients underwent full pulmonary function testing, a six-minute walk test, and quality of life assessment, as well as blood and urine sampling for quantification of MMP-2, MMP-9, and VEGF-D levels-at baseline, as well as at 6 and 12 months after the initiation of doxycycline.

RESULTS:

Thirty-one LAM patients received doxycycline for 12 months. Although there was effective blockade of urinary MMP-9 and serum MMP-2 after treatment, there were no significant differences between pre and post-doxycycline serum levels of MMP-9 and VEGF-D. On the basis of their response to doxycycline (as determined by the variation in FEV₁), the patients were divided into two groups: the doxycycline-responder (doxy-R) group (n = 13); and the doxycycline-nonresponder (doxy-NR) group (n = 18). The patients with mild spirometric abnormalities responded better to doxycycline. The most common side effects were mild epigastric pain, nausea, and diarrhea.

CONCLUSIONS:

In patients with LAM, doxycycline treatment results in effective MMP blockade, as well as in improved lung function and quality of life in those with less severe disease. However, these benefits do not seem to be related to the MMP blockade, raising the hypothesis that there is a different mechanism of action.     

盐酸多西环素治疗游泳池肉芽肿9例临床分析

目的分析游泳池肉芽肿的临床特点及应用盐酸多西环素治疗的疗效。方法回顾性分析2012年1月-2017年12月期间本院皮肤科门诊游泳池肉芽肿患者的临床资料,总结单独口服盐酸多西环素治疗效果。结果共收集9例患者,男4例,女5例,平均年龄(47.89±5.99)岁,平均病程(10.33±6.60)个月。所有皮损均累及上肢,5例皮损为局限性肉芽肿样斑块(Ⅰ型),4例皮损呈孢子丝菌病样沿淋巴管播散(Ⅱ型)。8例全程单一服用多西环素治疗,1例因胃肠道不适换用左氧氟沙星治疗。所有患者全部治愈,治愈平均时间是(2.28±0.67)个月。结论Ⅰ型和Ⅱ型游泳池肉芽肿可以单独使用盐酸多西环素治愈。     

莫西沙星治疗沙眼衣原体宫颈炎的疗效分析

目的观察莫西沙星治疗对沙眼衣原体性宫颈炎的疗效。方法选择沙眼衣原体性宫颈炎患者109例，随机分为A，B两组。A组58例：口服莫西沙星400mg，1次／d，疗程15d；B组51例：口服强力霉素100mg，2次／d，疗程15d。治疗完成后1—2周进行疗效评价。结果A组治愈54例（93．1％），B组治愈31例（60．8％），两组问治愈率比较差异有高度显著性（P〈0．01）。结论口服莫西沙星对沙眼衣原体性宫颈炎感染疗效好，毒副作用少，优于强力霉素。