一种体内恒速持续给药的方法—微量渗透泵

利用微量渗透泵给药是一种崭新的动物实验性持续给药方法。泵体由３个同心层（由内向外）—贮药池、渗透性套筒及控制渗透泵药物释放速度的半透膜组成。泵在被水激活后,因水可按渗透梯度渗入渗透性套筒部分,压迫泵体以恒定速度持续释放药物几天至若干星期,其渗透速度与被释放药物的理化性质无关,因而适用于多种药物     

抗生素缓控释给药系统——载药微球的研究与开发

利用具良好生物相容性和生物可降解性的聚合物制得的微球作为一种新型药物载体, 具有良好的缓控释作用,并具有一定的靶向性,可用于口服和注射,在药学领域和临床上有着广阔的应用前景。综述近年来各种抗生素缓控释微球制剂的研究与开发。     

氨甲喋呤不同给药途径治疗异位妊娠疗效分析

目的:探讨氨甲喋呤不同给药途径治疗异位妊娠的临床疗效。方法:将符合保守治疗指征的111例异位妊娠患者随机分成两组,A组57例采用氨甲喋呤50 mg肌注,B组54例为静脉滴注,两组均隔日一次用药共三次,次日加用甲酰四氢叶酸钙解毒6 mg,肌注共三次,定期测定血β-HCG至正常。结果:两组共有97例成功,总成功率为87.39％,其中A组有49例获得成功,成功率为85.96％,B组有48例获得成功,成功率为88.89％,两组成功率无显著性差异,P>0.05。结论:合理选择保守治疗的对象严格掌握适应症是MTX保守治疗成功的关键,至于MTX的两种不同给药途径所得疗效无明显差异。     

运用HPLC-MS对鸦胆子油自微乳给药系统肠吸收的研究

目的:建立高效液相色谱-串联质谱法检测油酸和亚油酸含量的方法,从而对鸦胆子油自微乳给药系统中鸦胆子油的肠吸收进行研究.方法:以甲醇-水(95∶5 v/v)为流动相,流速为0.4 mL/min,柱温为35℃作为高效液相色谱的检测条件.利用大鼠小肠膜建立体外药物扩散体系研究鸦胆子油的肠吸收特性.结果:油酸和亚油酸的保留时间分别为10.46± 0.02和8.55±0.01 min,线性范围分别为0.50～50.0 ng/mL和5.06～101.2 ng/mL,平均绝对回收率分别为97.49±3.11％和105.76± 3.13％.日间和日内精密度都小于5％.在肠吸收实验中,鸦胆子油自微乳体系中测得油酸和亚油酸含量是单独给予鸦胆子油测得量的2.8和4.1倍.结论:该方法高效、灵敏、选择性高,可以用于鸦胆子油及鸦胆子油自微乳肠吸收中油酸和亚油酸的质量测定.     

载MD-CPT透明质酸纳米微乳经皮给药作用于瘢痕修复的研究

喜树碱衍生物对瘢痕疙瘩成纤维细胞的增殖有明显的抑制作用,为提高药物利用度,提供透皮给药的治疗途径,本文采用微乳法制备了一种新的O/W型透明质酸纳米载体(HA-GMS),包载药物10,11-亚甲二氧基喜树碱(MD-CPT),制备过程中无酒精,且没有使用化学增强剂,经透射电镜和激光粒度仪分别测得HA-GMS纳米乳粒径为(177.33±27.11)nm,zeta电位为-15.6±1.7,多分散系数为0.55±0.01,纳米微乳对MD-CPT药物的包封率为(77.85±1.29)%,且稳定性良好.用MTT法检测HA-GMS对人正常细胞HSF、HUVECs的作用,细胞相对存活率为75%~95%,生物相容性良好,用HA-GMS对瘢痕疙瘩成纤维细胞培养48 h,其生长抑制率为28.2%.HA-GMS纳米乳运载的MD-CPT皮肤渗透量明显高于对照组MD-CPT乙醇溶液对皮肤的渗透量,作用4 h的累积渗透量分别为(660.72±20.54)μg/cm2和(102.73±13.81)μg/cm2,HA-GMS纳米乳明显增加了MD-CPT的透皮效率,本研究结果为透皮给药治疗瘢痕疾病提供了基础.     

冠脉内注射替罗非班不同给药方式对急性心肌梗死介入治疗术中血流异常的影响

目的：比较急性心肌梗死介入治疗中冠脉内常规给予以及必要时给予血小板膜糖蛋白（GP）Ⅱb／Ⅲa受体拮抗剂替罗非班两种给药方式对冠脉血流异常的影响,寻找较好的替罗非班用药方式。方法：入选九四医院2005年1月至2008年10月急性心肌梗死直接PCI患者58例,随机分成常规给药组（血管开通前所有患者冠状动脉内均注射替罗非班,n=30）与必要时给药组（血管开通后即时造影显示TIMI血流≤2级者冠脉内注射替罗非班,TIMI血流3级者不给药,n=28）,观察支架植入后30分钟TIMI血流、30天内主要不良心血管事件（MACE）、出血以及血小板减少情况。结果：必要给药组冠脉内给药可显著改善冠脉血流（TIMI3级给药前46．4％,给药后75％,P〈0．05）,常规给药组支架植入后30分钟TIMI3级获得率高于必要给药组（96．7％比75％,P〈0．05）,MACE、出血和血小板减少事件两组之间差异无统计学意义。结论：冠脉内给予替罗非班可有效降低急性心肌梗死PCI术中血流异常情况,血管开通前冠脉内常规给药方式优于必要时给药方式。     

阿奇霉素连续与间歇注射给药治疗支原体肺炎的疗效与耐药性比较

为了比较阿奇霉素连续与间歇注射两种给药方式治疗支原体肺炎的临床疗效及耐药性,选取120例支原体肺炎患者,随机分为连续给药组(A组)与间歇给药组(B组),两组患者均连续治疗1个疗程(14d),比较临床疗效及耐药性情况。结果显示,两组患者在临床疗效、症状及体征消失时间方面均无明显差异(p>0.05),但治疗7d、14d后A组的最小抑菌浓度(MIC)值均明显低于B组(p<0.05)。结果表明,阿奇霉素的两种不同给药方式治疗支原体肺炎效果类似,但间歇给药法可减轻因连续给药带来的耐药性,对提高抗生素用药安全有一定价值。     

奥美拉唑不同给药方式治疗新生儿应激性溃疡的效果分析

目的:探讨奥美拉唑不同给药方式治疗新生儿应激性溃疡的临床效果及安全性。方法:选取2014年1月～2018年6月我院收治的应激性溃疡新生儿61例,根据随机数字表法分为两组,对照组患儿给予奥美拉唑0.6 mg/kg胃管注入治疗,观察组患儿给予奥美拉唑2 mg/kg持续24 h微泵静脉滴注。比较两组患儿的临床治疗效果、临床症状缓解时间、止血时间、胃肠喂养开始时间、p H值和不良反应的发生情况。结果:治疗后,两组患儿的临床总有效率比较无统计学差异(P0.05);观察组患儿临床症状消失时间和止血时间均显著短于对照组(P0.05),喂养开始时间≤24 h的患儿比例高于对照组,喂养开始时间≥72 h的患儿比例显著低于对照组(P0.05),pH值显著高于对照组(P0.05)。两组患儿治疗期间均未发生恶心、呕吐、便秘、皮疹等不良反应,且肝肾功能未受明显影响。结论:2 mg/kg奥美拉唑持续24 h微泵静脉滴注与0.6 mg/kg胃管注入治疗的临床总有效率相当,但微泵静脉滴注可显著提高患儿的pH值,缩短临床症状恢复时间、止血时间和胃肠喂养开始时间,且安全性高。     

维生素E自微乳化给药系统的制备

目的:研究维生素E自微乳的制备工艺.方法:考察了维生素E在不同油、乳化剂、助乳化剂中的溶解情况,筛选油相、乳化剂和助乳化剂.以假三角相图中形成微乳的面积为指标,采用正交设计表对处方进行优化,确定维生素E自乳化给药系统的最佳处方.结果:微乳最佳处方:油酸乙酯:Tween-80:丙二醇的比例为3:4:3.结论:该处方自乳化区域大,自微乳化速率快,所形成的乳剂稳定.     

枯草杆菌二联活菌制剂鼻饲给药治疗昏迷患者抗生素相关性腹泻的疗效观察

目的：研究枯草杆菌二联活菌制剂经鼻饲给药治疗昏迷患者抗生素相关性腹泻的临床疗效。方法：收集以2011 年1 月至 2014 年1 月本院确诊的76 例患抗生素相关性腹泻的昏迷患者作为研究对象,按随机数字表法分为对照组(38 例)和试验组(38 例),对照组在基础治疗的基础上给予鼻饲蒙脱石散收敛止泻治疗,而试验组在对照组的基础上,同时给予枯草杆菌二联活菌胶囊 （美常安）鼻饲给药治疗。对比治疗前后两组患者的症状改善情况以及粪便实验室检查指标,记录两组不良反应。结果：除治疗过 程中死亡4 例、意识转清停止鼻饲8 例外,试验组33 例,对照组31 例完成试验。试验组治疗有效率明显高于对照组的(X2=2.627, P <0.05)。给药第6d 试验组的白细胞转阴率为81.8%,明显高于对照组的30%(P<0.05),给药第6 d 及治疗后试验组的肠道菌群纠 正率分别为84.2%、94.7%,明显高于对照组的41.2%、64.7%,差异均有统计学意义(P<0.05)。对照组患者不良反应的发生率明显高 于试验组（P<0.05）。结论：枯草杆菌二联活菌制剂鼻饲给药可显著改善昏迷患者抗生素相关性腹泻的症状,使肠道菌群更快得以 纠正、缓解使肠道炎症,且安全性高,值得临床推广使用。     

Effective Treatment of Respiratory Alphaherpesvirus Infection Using RNA Interference

Background

Equine herpesvirus type 1 (EHV-1), a member of the Alphaherpesvirinae, is spread via nasal secretions and causes respiratory disease, neurological disorders and abortions. The virus is a significant equine pathogen, but current EHV-1 vaccines are only partially protective and effective metaphylactic and therapeutic agents are not available. Small interfering RNAs (siRNA''s), delivered intranasally, could prove a valuable alternative for infection control. siRNA''s against two essential EHV-1 genes, encoding the viral helicase (Ori) and glycoprotein B, were evaluated for their potential to decrease EHV-1 infection in a mouse model.

Methodology/Principal Fndings

siRNA therapy in vitro significantly reduced virus production and plaque size. Viral titers were reduced 80-fold with 37.5 pmol of a single siRNA or with as little as 6.25 pmol of each siRNA when used in combination. siRNA therapy in vivo significantly reduced viral replication and clinical signs. Intranasal treatment did not require a transport vehicle and proved effective when given up to 12 h before or after infection.

Conclusions/Significance

siRNA treatment has potential for both prevention and early treatment of EHV-1 infections.     

机械通气辅助抗蛇毒血清抢救银环蛇咬伤致呼吸衰竭的临床分析

目的观察抗蛇毒血清和机械通气对银环蛇咬伤致呼吸衰竭的疗效。方法应用机械通气和抗蛇毒血清救治16例银环蛇咬伤致呼吸衰竭患者。结果16例病人全部救活。患者出现眼睑下垂,呼吸节律改变或呼吸困难时,及早予经鼻气管插管行机械通气和应用抗蛇毒血清,能有效地抢救蛇伤致呼吸衰竭患者生命。结论机械通气辅助抗蛇毒血清是救治银环蛇咬伤致呼吸衰竭的有效方法。     

泛福舒合穴位贴敷对治疗儿童反复呼吸道感染临床疗效分析

目的:探析泛福舒联合穴位贴敷对治疗儿童反复呼吸道感染的临床疗效.方法:选取2009年9月-2012年9月就诊于我院儿科的反复呼吸道感染的患儿60例随机分为两组,对照组给予常规抗生素加穴位(肺俞、膻中、天突、足三里)贴敷(每次12小时,隔日1次,15次为一个疗程)治疗;观察组在此基础上加用泛福苏治疗(3.5 mg,每天清晨空腹顿服,连服10天,停20天为一个疗程),两组均治疗3个疗程后,随诊6个月,观察对比两组患者治疗效果、免疫指标、用药不良反应、远期疗效等.结果:观察组在发热天数、咳嗽天数和抗生素使用时间上都明显少于对照组,两组相比具有统计学意义(P＜0.05);免疫指标治疗前后比较中,对照组各免疫指标治疗前后均没有明显改变,观察组血清IgG在治疗后明显升高,具有统计学差异(P＜.05),IgA在治疗后升高,但没有显著差异,IgM治疗后基本没有改变;观察组远期疗效明显优于对照组,两组相比具有统计学意义(P＜0.05).结论:泛福舒联合穴位贴敷对治疗儿童反复呼吸道感染临床效果显著,治疗有效率高,具有积极的临床意义,值得推广.     

脑卒中昏迷患者气管切开后并发肺部感染的病原菌分布及预防对策

目的:探讨脑卒中昏迷患者气管切开后并发肺部感染的病原菌分布及危险因素,并提出预防措施。方法:回顾性分析2016年1月至2017年2月我院收治的脑卒中昏迷患者96例,分析脑卒中昏迷患者肺部感染发生率及病原菌分布情况,同时采用单因素和多因素logistic回归分析肺部感染的危险因素,从而提出相应的预防措施。结果:96例脑卒中昏迷患者气管切开术后肺部感染的发生率为48.96%(47/96);共分离培养病原菌104株,包括革兰阴性菌69株(66.35%)、革兰阳性菌20株(19.23%)和真菌15株(14.42%);单因素分析结果显示,脑卒中昏迷患者气管切开术后肺部感染与年龄、基础疾病、气管切开时间、卧床时间、使用广谱抗菌药物、吸烟史、人工气道、吸痰次数及雾化吸入次数密切相关(P0.05),而与患者性别、体重、脑卒中类型无关(P0.05);多因素logistic回归分析结果显示,年龄45岁、合并患有基础疾病、气管切开时间5 d、使用广谱抗菌药物、吸烟史及建立人工气道均为脑卒中昏迷患者气管切开术后肺部感染的危险因素(P0.05),ROC分析结果为:气管切开时间的临界点(阈值C)是4.3天,其灵敏度和特异度将分别为0.851和0.918。结论:脑卒中昏迷患者气管切开后并发肺部感染的病原菌以革兰阴性菌为主,年龄45岁、合并患有基础疾病、气管切开时间5 d、使用广谱抗菌药物、吸烟史及建立人工气道能够导致脑卒中昏迷患者气管切开术后发生肺部感染,并且气管切开时间超过4.3天,脑卒中昏迷患者肺部感染的风险将大大增加,应根据病原学特征及其危险因素,采取针对性措施,降低肺部感染的发病风险。     

Local IL-17A Potentiates Early Neutrophil Recruitment to the Respiratory Tract during Severe RSV Infection

Respiratory syncytial virus (RSV) bronchiolitis triggers a strong innate immune response characterized by excessive neutrophil infiltration which contributes to RSV induced pathology. The cytokine IL-17A enhances neutrophil infiltration into virus infected lungs. IL-17A is however best known as an effector of adaptive immune responses. The role of IL-17A in early immune modulation in RSV infection is unknown. We aimed to elucidate whether local IL-17A facilitates the innate neutrophil infiltration into RSV infected lungs prior to adaptive immunity. To this end, we studied IL-17A production in newborns that were hospitalized for severe RSV bronchiolitis. In tracheal aspirates we measured IL-17A concentration and neutrophil counts. We utilized cultured human epithelial cells to test if IL-17A regulates RSV infection-induced IL-8 release as mediator of neutrophil recruitment. In mice we investigated the cell types that are responsible for early innate IL-17A production during RSV infection. Using IL-17A neutralizing antibodies we tested if IL-17A is responsible for innate neutrophil infiltration in mice. Our data show that increased IL-17A production in newborn RSV patient lungs correlates with subsequent neutrophil counts recruited to the lungs. IL-17A potentiates RSV-induced production of the neutrophil-attracting chemokine IL-8 by airway epithelial cells in vitro. Various lung-resident lymphocytes produced IL-17A during early RSV infection in Balb/c mice, of which a local population of CD4 T cells stood out as the predominant RSV-induced cell type. By removing IL-17A during early RSV infection in mice we showed that IL-17A is responsible for enhanced innate neutrophil infiltration in vivo. Using patient material, in vitro studies, and an animal model of RSV infection, we thus show that early local IL-17A production in the airways during RSV bronchiolitis facilitates neutrophil recruitment with pathologic consequences to infant lungs.     

Mouse Model of Respiratory Tract Infection Induced by Waddlia chondrophila

Waddlia chondrophila, an obligate intracellular bacterium belonging to the Chlamydiales order, is considered as an emerging pathogen. Some clinical studies highlighted a possible role of W. chondrophila in bronchiolitis, pneumonia and miscarriage. This pathogenic potential is further supported by the ability of W. chondrophila to infect and replicate within human pneumocytes, macrophages and endometrial cells. Considering that W. chondrophila might be a causative agent of respiratory tract infection, we developed a mouse model of respiratory tract infection to get insight into the pathogenesis of W. chondrophila. Following intranasal inoculation of 2 x 10⁸W. chondrophila, mice lost up to 40% of their body weight, and succumbed rapidly from infection with a death rate reaching 50% at day 4 post-inoculation. Bacterial loads, estimated by qPCR, increased from day 0 to day 3 post-infection and decreased thereafter in surviving mice. Bacterial growth was confirmed by detecting dividing bacteria using electron microscopy, and living bacteria were isolated from lungs 14 days post-infection. Immunohistochemistry and histopathology of infected lungs revealed the presence of bacteria associated with pneumonia characterized by an important multifocal inflammation. The high inflammatory score in the lungs was associated with the presence of pro-inflammatory cytokines in both serum and lungs at day 3 post-infection. This animal model supports the role of W. chondrophila as an agent of respiratory tract infection, and will help understanding the pathogenesis of this strict intracellular bacterium.     

血清PCT联合痰培养检测在呼吸道感染疾病中的应用

目的:研究血清降钙素原(PCT)联合痰培养检测在呼吸道感染疾病中的应用价值。方法:选择2012年1月至2014年12月在我院接受治疗的呼吸道感染患者100例进行研究。分析痰培养菌群的分布情况以及PCT的检测结果,对比痰培养细菌感染者及真菌感染者的菌种分类及PCT检测结果。结果:检出病原菌的患者PCT水平均分别显著高于正常菌群及未见细菌生长的患者,差异均有统计学意义(均P0.05)。细菌感染PCT阳性比例与真菌感染相比,差异无统计学意义(P0.05)。细菌感染中,革兰氏阳性菌的PCT水平(0.74±0.33μg/L)与革兰氏阴性菌(0.72±0.24μg/L)对比,差异无统计学意义(P0.05)。真菌感染中,白假丝酵母菌及烟曲霉菌的PCT阳性比例最高,分别为60.00%及80.00%。结论:血清PCT与痰培养检测应用于评价有呼吸道感染的患者病情,具有一定的反馈意义,但无法确定患者的呼吸道感染究竟是细菌感染亦或是真菌感染。     

Increased Risk of Wheeze and Decreased Lung Function after Respiratory Syncytial Virus Infection

Background

A relationship between hospitalization for respiratory syncytial virus (RSV) bronchiolitis and asthma development has been suggested in case-control studies.

Objective

The aim of this study was to assess the risk of current wheeze, asthma, and lung function at school age in infants previously hospitalized for RSV bronchiolitis compared to non-hospitalized children.

Methods

For this study, data from a prospective birth cohort of unselected, term-born infants (n = 553), of whom 4 (0.7%) were hospitalized for RSV bronchiolitis, and a prospective patient cohort of 155 term infants hospitalized for RSV bronchiolitis were used. Respiratory outcomes at age 6 in children hospitalized for RSV bronchiolitis were compared to non-hospitalized children.

Results

The risk of current wheeze was higher in hospitalized patients (n = 159) compared to non-hospitalized children (n = 549) (adjusted odds ratio (OR) 3.2 (95% CI 1.2–8.1). Similarly, the risk of current asthma, defined as a doctor’s diagnosis of asthma plus current symptoms or medication use, was higher in hospitalized patients (adjusted OR 3.1 (95% CI 1.3–7.5). Compared to non-hospitalized children, RSV bronchiolitis hospitalization was associated with lower lung function (mean difference FEV1% predicted −6.8 l (95% CI (−10.2 to −3.4).

Conclusions and Clinical Relevance

This is the first study showing that hospitalization for RSV bronchiolitis during infancy is associated with increased risk of wheezing, current asthma, and impaired lung function as compared to an unselected birth cohort at age 6.