盐酸氨溴索对慢性阻塞性肺疾病患者急性期血清白细胞介素8及白细胞介素18的影响

目的 研究盐酸氨溴索对慢性阻塞性肺疾病(COPD)急性加重期白细胞介素8(IL)-8、IL-18的影响.方法 选择2007年11月至2009年11月住院的慢性阻塞性肺疾病患者82例,入院时均为急性加重期,肺功能中度.完全随机分为观察组50例,对照组32例.观察组在常规治疗基础上加用盐酸氨溴索注射液30 mg+5%葡萄糖注射液250 ml静脉滴注,2次/d,疗程14 d;对照组仅给予常规治疗,疗程14 d.分别观察2组治疗前后血清IL-8、IL-18水平.结果 对照组及观察组治疗后IL-8、IL-18水平分别为(139.81±42.38)ng/L、(64.2±19.6)ng/L及(89.27±30.68)ng/L、(49.8±17.9)ng/L.2组治疗后血清IL-8、IL-18水平均低于治疗前,差异具有统计学意义(P＜0.05);观察组治疗后血清IL-8、IL-18水平低于对照组,差异具有统计学意义(P＜0.05).结论 盐酸氨溴索可以抑制COPD患者血清IL-8、IL-18的释放,可能有一定的肺保护和治疗作用.

Abstract：

Objective To study the effect of ambroxo1 on interleukin (IL)-8, IL-18 in chronic obstructive pulmonary disease (COPD). Methods Eighty-two patients with acute exacerbation of chsonic obstructive pulmonary disease (AECOPD) between 2007 and 2009 were enrolled, according to the guidelines for COPD treatment. All patients were in acute period with middle level lung dysfunction. They were divided into two groups: conventional therapy (n = 32 ), conventional and interferential therapy ( n = 50). The treatment group was given conventional therapy plus ambroxol for 14 days. The levels of IL-8,IL-18 in serum before-and-after therapy in two groups were observed. Results The level of IL-8, IL-18 in serum of two groups after therapy was lower than that before therapy (P ＜0.05). In the group of conventional plus interferential theraphy,the level of IL-8 ,IL-18 in serum after therapy were lower than that of conventional therapy ( P ＜ 0.05). Conclusion Ambroxol can inhibit the release of IL-8,IL-18 in serum of COPD patients.     

氨溴索诱导痰在老年慢性阻塞性肺疾病患者气道炎症中的应用

目的 观察老年慢性阻塞性肺疾病(COPD)患者氨溴索诱导痰的安全性及有效性和急性加重期及稳定期老年COPD患者氨溴索诱导痰中细胞组分和可溶性介质水平变化,探讨其在气道炎症中的作用.方法 将老年COPD急性加重期患者40例随机分为氨溴索组和高渗盐水组,每组20例.高渗盐水组雾化吸入3%高渗盐水4ml,氨溴索组给予3%高渗盐水2ml+氨溴索2ml诱导排痰.对比2组患者不良反应发生率、排痰成功率、痰液中细胞组分及炎性递质含量.测定氨溴索组患者急性加重期、稳定期诱导痰中细胞总数、单核细胞百分比、中性粒细胞百分比、白细胞介素-8(IL-8)及肿瘤坏死因子-α(TNF-α)浓度及其第1秒用力呼气容积(FEV1)、FEV1占预计值百分比.结果 2组不良反应发生率、排痰成功率比较差异均有统计学意义(P＜0.05).氨溴索组患者急性加重期诱导痰液中细胞总数、单核细胞百分比、中性粒细胞百分比、IL-8及TNF-α浓度与稳定期比较,差异均有统计学意义(P＜0.05);氨溴索组患者痰液中细胞总数、单核细胞及中性粒细胞百分比、IL-8及TNF-α浓度和FEV1占预计值百分比呈负相关(急性加重期及稳定期r值分别为-0.728、-0.793、-0.816、-0.794、-0.605及-0.635、-0.746、-0.721、-0.658、-0.654).结论 氨溴索诱导痰是一种安全、有效的方法,在阐明老年COPD患者气道炎症的发生、发展及病情检测中有指导意义.     

氨溴索对COPD患者气道炎症影响的临床研究

目的 探讨氨溴索对慢性阻塞性肺疾病(COPD)患气道炎症的影响。方法 选择50例COPD急性发作期患，随机分组，并选取健康老年人25例为对照组，观察其血清及痰液的IL—6、IL—8及TNF—α的变化。结果 氨溴索治疗组和对照组患的痰液及血液IL—6、IL—8及TNF—α含量高于正常组，两组治疗前无显差异，治疗10天后，A组水平较B组下降(P＜0．01)。结论 氨溴索可以抑制COPD急性加重期患的气道局部及全身炎症反应过程，它的应用有利于COPD患病情的恢复。     

TNF-α及IL-8检测在慢性阻塞性肺疾病中的意义

目的:探讨肿瘤坏死因子-α(TNF-α)及白介素-8(IL-8)在慢性阻塞性肺疾病(COPD)发病机制中的作用.方法:收集28例COPD急性加重期患者,25例COPD缓解期患者和30例健康者的静脉血,离心后取血清,采用酶联免疫法(ELISA)测定其中TNF-α及IL-8水平,同时对COPD急性期患者常规测定动脉血PaO2、PaCO2.结果:COPD急性加重期患者血清TNF-α及IL-8水平明显高于缓解期及健康对照组,缓解期明显高于对照组(P＜0.05);COPD急性加重期血中TNF-α及IL-8含量与PaO2成负相关,与PaCO2呈正相关.结论:TNF-α及IL-8参与了COPD气道炎性反应,TNF-α及IL-8检测对COPD诊断和预后判断具有积极作用.     

氧驱雾化吸入噻托溴铵联合盐酸氨溴索治疗老年COPD急性加重期的临床研究

目的 探讨噻托溴铵+盐酸氨溴索氧驱雾化吸入方案在慢性阻塞性肺疾病(COPD)急性加重期老年患者中的临床应用价值.方法 将92例处于急性加重期的COPD老年患者随机分成联合组(n=46)和对照组(n=46).对照组采用盐酸氨溴索氧驱雾化吸入方案,联合组采用噻托溴铵+盐酸氨溴索氧驱雾化吸入方案.比较两组患者治疗前后动脉血气指标及6 min步行试验(6 MWD)、圣乔治呼吸问卷(SGRQ)评估结果变化差异,记录其不良反应发生情况.结果 ①治疗2周后,两组患者PaO2水平及6MWD评估结果均较治疗前显著提升,且PaCO2水平和SGRQ评分均较治疗前显著降低(P＜0.05);其中联合组上述指标变化幅度均大于对照组患者(P＜0.05);②两组患者用药后均无严重不良反应发生,且轻微不良反应(6.5％vs.4.3％)组间比较差异无统计学意义(P＞0.05).结论 将噻托溴铵+盐酸氨溴索氧驱雾化吸入方案应用于老年COPD患者中,疗效确切且治疗安全性突出,于患者预后提升有利.     

乌司他丁对COPD急性加重期患者氧化/抗氧化失衡的影响

目的 探究乌司他丁对慢性阻塞性肺疾病(COPD)急性加重期患者氧化/抗氧化失衡的影响.方法 将本院2014年11月至2016年11月收治的100例COPD急性加重期患者随机分为观察组(n=50)和对照组(n=50),对照组采用常规治疗,观察组在对照组基础上加用乌司他丁静脉注射,比较两组治疗前后超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-PX)等氧化/抗氧化指标水平和一秒钟用力呼气容积占用力肺活量百分比(FEV 1/FVC)、动脉血氧分压(PaO2)、动脉二氧化碳分压(PaCO2)、pH水平.结果 两组治疗后氧化/抗氧化指标均有显著改善(均P＜0.05),且观察组治疗后SOD、MDA、GSH-PX水平显著优于对照组(均P＜0.05);两组治疗后肺功能及血气分析指标均有显著改善(均P＜ 0.05),且观察组治疗后FEV1/FVC、PaO2、PaCO2、pH水平显著优于对照组(均P＜ 0.05).结论 乌司他丁治疗COPD急性加重期疗效显著,能有效调节机体氧化/抗氧化平衡,值得在临床上广泛推广.     

氨溴索对慢性阻塞性肺疾病患者氧化应激的影响

目的：研究氨溴索针剂对慢性阻塞性肺疾病（COPD）急性加重期患者氧化与抗氧化能力的影响。方法：COPD急性加重期患者,采用氨溴索针剂治疗,检测患者血清丙二醛（MDA）、超氧化物歧化酶活性（SOD）水平。并比较两组患者总有效率。结果：氨溴索治疗显著降低患者血清MDA含量,显著增加SOD水平,总有效率提高。结论：氨溴索能减轻COPD急性加重期患者氧化应激程度,提高患者抗氧化能力,对COPD患者有一定辅助治疗价值。     

不同时期慢性阻塞性肺疾病患者血清炎性因子水平和肺功能情况分析

目的 探讨不同时期慢性阻塞性肺疾病(COPD)患者血清炎性因子水平和肺功能情况.方法 选择2013年2月-2015年2月收治的COPD 200例,分为急性加重期组和稳定期组,每组100例.选择同期健康体检者100例作为对照组.检测3组血清炎性因子水平和肺功能,并探讨二者的相关性.结果 急性加重期组和稳定期组白介素-1β (IL-1β)、IL-6、IL-8、肿瘤坏死因子-α(TNF-α)、干扰素-γ(IFN-γ)和结缔组织生长因子(CTGF)均高于对照组,IL-2低于对照组(P＜0.05);急性加重期组IL-2低于稳定期组,其余指标均高于稳定期组(P＜0.05).稳定期组和急性加重期组肺功能各指标均低于对照组,且急性加重期组低于稳定期组(P＜0.05).结论 IL-1β、IL-8、IL-2、TNF-α、IL-6、CTGF和IFN-γ是评估COPD病情的重要指标,对临床治疗具有一定的指导作用.     

盐酸氨溴索治疗COPD急性加重期的临床观察

目的 观察盐酸氨溴索治疗慢性阻塞性肺疾病(COPD)急性加重期的临床疗效及用药安全性.方法 选择2008年11月至2010年11月收治的COPD急性加重期患者82例,按随机化原则分为观察组和对照组各41例,两组均给予吸氧、抗感染、解痉平喘、应用糖皮质激素及对症处理等常规综合治疗,观察组在常规治疗基础上加用盐酸氨溴索治疗.观察两组临床疗效及不良反应.结果 观察组显效22例(53.66％),有效14例(34.15％),总有效率为87.80％;对照组显效12例(29.27％),有效16例(39.02％),总有效率为68.29％.观察组显效率和总有效率均明显高于对照组,差异有统计学意义(P＜0.05).观察组发生不良反应1例,表现为食欲不振、腹泻,经对症处理后好转,未影响继续治疗.其余患者未出现明显不良反应.结论 COPD急性加重期临床治疗过程中在常规综合治疗基础上加用盐酸氨溴索疗效确切,用药安全性好,值得临床推广应用.     

异丙托溴铵联合盐酸氨溴索雾化吸入治疗慢性阻塞性肺疾病急性加重期疗效观察

目的 探究异丙托溴铵联合盐酸氨溴索雾化吸入治疗慢性阻塞性肺病（COPD）急性加重期.方法 回顾性分析2010年7月-2011年7月在都昌县人民医院接受治疗的COPD患者106例.根据不同的治疗方法进行分组,对照组患者53例,采用抗炎、平喘、祛痰、吸氧治疗.治疗组患者53例,在对照组基础上加用异丙托溴铵联合盐酸氨溴索雾化吸入治疗,比较两组患者治疗前后动脉血氧分压（PaO2）和动脉血二氧化碳分压（PaCO2）.结果 两组患者治疗前PaO2和PaCO2检测值比较差异无统计学意义（P＞0.05）;治疗后,治疗组PaO2检测值高于对照组,PaCO2检测值低于对照组,差异有统计学意义（P＜0.05）.治疗组有效率高于对照组,差异有统计学意义（P＜0.05）.结论 异丙托溴铵联合盐酸氨溴索雾化吸入治疗COPD急性加重期疗效明显,并能改善血氧浓度,值得临床推广.     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg.kg) or i.p. (50 mg.kg) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) l.h. kg in the male rat and 10.6 (95% CI: 7.5, 15.0) l.h. kg in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p 0.001) in plasma obtained from the male (8.8 2.0%) compared with the female rat (11.7 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Theophylline kinetics in peripheral tissues in vivo in humans

Several biochemical and cellular effects have been described for methylxanthines under in vitro conditions. However, it is unknown, whether threshold concentrations required to exert these effects are attained in target tissues in vivo. We therefore employed the microdialysis technique for measuring theophylline concentrations in peripheral tissues under in vivo conditions.Following in vitro and in vivo calibration, microdialysis probes were inserted into the medial vastus muscle and into the periumbilical subcutaneous adipose layer of healthy volunteers. Following single oral dose administration of 300 mg or i.v. infusion of 240 mg theophylline, in vivo time courses of theophylline concentrations were monitored in tissues and plasma. Major pharmacokinetic parameters (c_max, t_max, AUC) were calculated for plasma and tissue time courses. The mean AUC_tissue /AUC_plasma-ratio was 0.56 (p.o.) and 0.55 (i.v.) for muscle and 0.55 (p.o.) and 0.72 (i.v.) for subcutaneous adipose tissue.We conclude that microdialysis provides important information on the distribution and the tissue pharmacokinetics of theophylline.Abbreviations FPIA Fluorescence polarisation immuno assay - AUC Area under the curve - t_max Time to peak concentration - c_max Peak concentration     

Quantitative in vivo and in vitro sex differences in artemisinin metabolism in rat

1. The pharmacokinetics of the antimalarial compound artemisinin were compared in the male and female Sprague-Dawley rat after single dose i.v. (20 mg x kg(-1)) or i.p. (50 mg x kg(-1)) administration of an emulsion formulation. 2. Plasma clearance of artemisinin was 12.0 (95% confidence interval: 10.4, 13.0) 1 x h(-1) x kg(-1) in the male rat and 10.6 (95% CI: 7.5, 15.0) 1 x h(-1) x kg(-1) in the female rat suggesting high hepatic extraction in combination with erythrocyte uptake or clearance. Artemisinin half-life was approximately 0.5 h after both routes of administration in both sexes. Values for plasma clearance and half-lives did not statistically differ between the sexes. 3. After i.p. administration artemisinin AUCs were 2-fold higher in the female compared with male rat (p < 0.001). Artemisinin disappearance was 3.9-fold greater in microsomes from male compared with female livers and it was inhibited in male microsomes by goat or rabbit serum containing antibodies against CYP2C11 and CYP3A2 but not CYP2B1 or CYP2E1. 4. The unbound fraction of artemisinin in plasma was lower (p < 0.001) in plasma obtained from the male (8.8 +/- 2.0%) compared with the female rat (11.7 +/- 2.2%). 5. The possibility of a marked sex difference, dependent on the route of administration, has to be taken into account in the design and interpretation of toxicological studies of artemisinin in this species.     

Interindividual variability in metabolic activation in humans in vivo

In assessing interindividual variability in metabolic activation, the toxic metabolite is often too unstable for conventional analysis. Possible alternatives include a stable product of the reactive metabolite e.g. cysteinyl derivatives of N-acetyl-4-benzoquinoneimine, the toxic metabolite of paracetamol, adducts with DNA or protein, and indirect measurement of the activity of the enzyme(s) producing the active metabolite. An example of the last approach is the use of furafylline, a highly specific inhibitor of human CYP1A2, to determine the extent of the metabolic activation of the cooked food mutagens PhIP and MeIQx. The extent of inhibition, determined from levels of unchanged amine in urine, is an indirect measure of the activity of the activation pathway. Further refinement of this approach, allied to improved measures of the biological process of interest should prove of value in evaluating interindividual variability and its role in the risk assessment process.     

休克时血中氧自由基的变化

本实验测定10名休克患者血浆和红细胞的丙二醛(MDA)、血浆总抗的氧化活性(AOA)的含量。结果表明:休克病人红细胞膜和血浆 MDA 含量(4.298±0.722;5.348±0.834)与对照组(3.235±0.682;4.356±1.081)比较明显增高(P<0.05);血浆 AOA(39.65±7.858)与对照组(48.21±10.81)比较明显降低(P<0.01)。提示:休克时,患者机体内自由基反应增强是引起组织细胞损伤的原因之一。     

Hyperkalaemia in patients in hospital

A survey of all laboratory blood specimens with a plasma potassium concentration greater than or equal to 5.5 mmol/L was conducted over a three month period. Of 331 specimens with hyperkalaemia, 71 were excluded because the specimens was haemolysed, old or contaminated. The laboratory served a population of 348,561 and during this time measured the plasma potassium on 25,016 occasions. Sixty-six outpatients and 20 neonates were not evaluated. The survey was undertaken on 86 of 102 inpatients (46 males), 48 of whom were over 66 years of age. Fifty-seven patients were admitted under a medical service and 29 under a surgical service. Fifty-nine had a single episode of hyperkalaemia. Thirty-two underwent a surgical procedure. The commonest contributing factor was impaired renal function which was present in 71 (83%) patients. Although a definitive causative role for drugs could be identified in only five patients, in 52 (60%) patients drugs were a contributing factor (potassium supplements 24, ACE inhibitors 16, nonsteroidal antiinflammatory drugs 12). Thirty-five of the 86 (41%) patients died during their hospital admission. Nineteen of the 35 deaths occurred within three days of the hyperkalaemia being recorded. A normal plasma potassium was eventually documented in 50 of the 86 patients. Of the remaining 36 patients, 25 (69%) subsequently died. In general the treatment of patients with hyperkalaemia focused on identifying and treating the underlying cause. Hyperkalaemia must always be considered seriously and regard given to the overall clinical status of the patient, with particular attention to drug therapy, renal and cardiac function, acid base status and the possibility of sepsis.     

Changes in angiopoietin expression in glomeruli involved in glomerulosclerosis in rats with daunorubicin-induced nephrosis

AIM: To study the potential pathological role of endogenous angiopoietins in daunorubicin-induced progressive glomerulosclerosis in rats. METHODS: Seventy male Wistar rats were allocated randomly into a daunorubicin group (DRB; n=40) or a control group (n=30). The rats in the DRB group were injected with DRB (15 mg/kg), in their tails. Subsequently, at intervals of 1, 2, 4, 6, 8, and 12 weeks, 5 male Wistar rats in each group were chosen randomly for 24 h urinary protein quantitative measurements (24 h UPQM), and determination of plasma tumor necrosis factor alpha (TNF-alpha), angiopoietin-1 (Ang1), and angiopoietin-2 (Ang2) levels. Kidney sections were examined by electron microscopy, Periodic Acid Schiff (PAS) staining, immunohistochemical staining and in situ hybridization histochemistry. RESULTS: As glomerulosclerosis progressed in the DRB group, expression of Ang1 mRNA and protein in glomeruli decreased and expression of TNF-alpha protein, Ang2 mRNA and protein in glomeruli increased. Expression of Ang1 mRNA and protein in glomeruli were negatively correlated with 24 h UPQM, Fn protein expression, and mean area of extracellular matrix (MAECM). In comparison, expression of Ang2 mRNA and protein in glomeruli were positively correlated with 24 h UPQM, Fn protein expression and MAECM; furthermore, there was a positive correlation between plasma Ang2 and 24 h UPQM. Plasma TNF-alpha and expression of TNF-alpha in glomeruli were positively correlated with expression of Ang2 mRNA and protein in glomeruli. There was a negative correlation between Ang1 protein expression and Ang2 protein expression in glomeruli. CONCLUSION: During DRB-induced glomerulosclerosis, podocyte injury led to a shift in the balance of Ang1 and Ang2 in glomeruli. Increased TNF-alpha in plasma and glomeruli may upregulate Ang2 expression in glomeruli. Elevated Ang2 in both plasma and glomeruli may mediate protein permeability through the glomerular filtration barrier. Moreover, local expression of Ang2 may facilitate the progress of glomerulosclerosis by upregulating a component expression of extracellular matrix.