慢性阻塞性肺疾病患者血清C反应蛋白和白介素-6的表达及相关性研究

目的:探讨慢性阻塞性肺疾病(COPD)患者急性加重期血清C反应蛋白(CRP)、白介素-6(IL-6)的变化及其相关性,分析其临床意义。方法:选择COPD急性加重期患者66例,健康对照组52例,分别测定COPD患者急性加重期、缓解期及健康对照者血清CRP,IL-6水平,进行统计学分析。结果:COPD组急性加重期及缓解期血清CRP,IL-6水平均明显高于健康对照组(P<0.01);COPD组急性加重期血清CRP,IL-6水平均明显高于缓解期(P<0.01);慢性阻塞性肺疾病急性加重期(AECOPD)合并呼吸衰竭组血清CRP,IL-6水平均明显高于单一AECOPD组(P<0.01);COPD组急性加重期血清CRP与IL-6呈正相关(r=0.516,P<0.05)。结论:血清CRP,IL-6可以用于AECOPD患者的早期诊断,且对患者病情的严重程度有一定的评估作用;血清CRP,IL-6联合测定对预测AECOPD的严重性和疗效的观察有一定的价值。     

乌司他丁对慢性阻塞性肺疾病炎性因子的影响

目的探讨乌司他丁对慢性阻塞性肺疾病急性加重期(AECOPD)炎性细胞因子的影响。方法慢性阻塞性肺疾病急性加重患者随机分为两组,治疗组在综合治疗基础上加用乌司他丁,对照组为综合治疗,治疗前后观察血清细胞因子(IL-8、TNF-α、IL-6)的变化。结果两组治疗后均能降低血清TNF-α、IL-8、IL-6的表达,且治疗组优于对照组。结论乌司他丁能降低AECOPD患者血清中IL-8、TNF-α、IL-6的表达。     

血清IL-8、TNF-α及IGF-Ⅰ检测在慢性阻塞性肺疾病急性加重期的临床意义

目的观察慢性阻塞性肺病(COPD)患者急性加重期外周血白细胞介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)、胰岛素样生长因子-Ⅰ(IGF-Ⅰ)指标变化。方法选择我院住院的COPD急性加重期患者60例,开始治疗前采用ELISA方法检测血清IL-8、TNF-α及IGF-Ⅰ水平,并与同期住院60例COPD缓解期患者和60例健康体检者进行比较。结果 COPD急性加重期患者IL-8、TNF-α及IGF-Ⅰ浓度明显高于COPD缓解期组和对照组(P<0.05),同时COPD缓解期患者血清IL-8、TNF-α及IGF-Ⅰ浓度也明显高于对照组(P<0.05)。结论 COPD急性加重期患者IL-8、TNF-α及IGF-Ⅰ明显升高,其参与了COPD的发生、发展。COPD缓解期虽然炎症明显减轻;但细胞因子仍持续升高并持续引起组织损伤。IL-8、TNF-α、IGF-Ⅰ等细胞因子的监测在慢性阻塞性肺疾病的诊疗指导中有重要临床意义。     

银杏叶提取物对慢性阻塞性肺疾病急性加重期患者白细胞介素-8和肿瘤坏死因子-α的影响

目的观察银杏叶提取物治疗慢性阻塞性肺疾病急性加重期(AECOPD)患者白细胞介素-8(IL-8)和肿瘤坏死因子-α(TNF-α)的影响。方法 AECOPD患者96例随机分为治疗组(50例)和对照组(46例),对照组给予常规对症治疗(吸氧、化痰、平喘、抗感染等),治疗组在常规治疗基础上加用银杏叶提取物制剂(金纳多注射液)20 mL加入0.9%氯化钠注射液250 mL静滴,1次/d,疗程14 d。观察两组患者症状体征、血气分析及肺功能指标的变化,同时检测两组患者血清IL-8和TNF-α水平的变化。结果治疗组总有效率优于对照组(P<0.05);治疗组血清中IL-8和TNF-α浓度较对照组下降,差异有统计学意义(P<0.05或0.01)。结论银杏叶提取物可降低AE-COPD血清中IL-8和TNF-α浓度,抑制炎症细胞生成,对AECOPD气道炎症具有明显的抑制作用。     

乌司他丁对慢性阻塞性肺病急性加重期合并呼吸衰竭的治疗作用

目的观察乌司他丁对慢性阻塞性肺病急性加重期(AECOPD)的治疗作用。方法选择40例AECOPD患者随机分为两组,对照组和观察组各20例。对照组采用常规治疗,观察组在常规治疗基础上予以乌司他丁10万单位加入100mL生理盐水静脉滴注,2次/日,连用7天。治疗过程中记录患者ICU住院时间、呼吸机使用时间,检测患者住院时、住院3天、住院7天CRP、TNF-α、IL-6、白细胞计数水平。结果观察组ICU住院时间、呼吸机使用时间,患者CRP、TNF-α、IL-6、白细胞计数水平均低于对照组,差异有统计学意义(P<0.01或P<0.05)。结论乌司他丁治疗慢性阻塞性肺病急性加重期效果较好,能缩短患者呼吸机使用时间及ICU住院时间。     

2型糖尿病患者血清hsCRP、TNF-α及IL-6的表达及相关性分析

目的 分析高敏C反应蛋白(CRP)、肿瘤坏死因子-αa(TNF-α)、白细胞介素-6(IL-6)在2型糖尿病患者血清的表达及相关性,探讨它们在2型糖尿病发病过程中的作用及意义.方法 分别测定32例健康人群(对照组)和32例2型糖尿病患者(实验组)血清hsCRP、TNF-α、IL-6水平,并采用SPSS 13.0软件对实验数据进行统计分析.结果 对照组hsCRP、TNF-α、IL-6的血清浓度值明显低于实验组,两者之间的差异十分显著(P=0.000).实验组hsCRP、TNF-α、IL-6三者之间存在明显相关性.结论 hsCRP、TNF-α、IL-6在2型糖尿病患者血清中明显增高且存在明显相关.提示三者可能参与了2型糖尿病的发病过程,其检测对2型糖尿病的诊断和预后具有潜在的临床价值.     

慢性阻塞性肺疾病加重期伴发糖尿病患者炎性因子检测

<正>慢性阻塞性肺疾病(COPD)是发病率及病死率逐年上升的常见病,是人类生命的主要杀手之一[1]。研究表明纤维蛋白原、白细胞介素等是慢性阻塞性肺疾病急性加重期(AECOPD)的血清学炎性标志物指标[2]。本研究通过对AECOPD伴发糖尿病患者纤维蛋白原(Fg)、超敏C反应蛋白(hsCRP)、白细胞介素(IL)-6、IL-8、肿瘤坏死因子-α(TNF-α)检测,进一步探讨COPD加重期伴发糖尿     

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.     

慢性阻塞性肺疾病患者血清白介素-17、基质金属蛋白酶-9水平测定及其意义

目的:通过测定慢性阻塞性肺疾病患者及正常人血清中白介素-17(IL-17)、基质金属蛋白酶-9(MMP -9)水平,探讨血清IL-17、MMP-9含量变化及其在慢性阻塞型肺疾病发病中的意义。方法:对慢性阻塞型肺疾病急性加重期及缓解期患者各30例,健康对照组28例,分别采用酶联免疫吸附试验(ELISA)法测定三组人群血清IL- 17、MMP-9水平,并同时测第一秒用力呼气容积(FEV1)占预计值的百分比。结果:COPD急性加重期、缓解期患者血浆IL-17、MMP-9水平均高于健康对照组,差异有统计学意义(P<0.01);急性加重期血浆IL-17水平高于缓解期,差异有统计学意义(P<0.01);急性加重期血浆MMP-9水平高于缓解期,差异无统计学意义(P>0.05);COPD急性加重期、缓解期患者血浆IL-17与MMP-9水平无相关性P>0.05;急性加重期、缓解期患者血浆IL-17均与FEV1. 0%占正常预计值均呈负相关(r=-0.772,P<0.05;r=-0.49,P<0.05);急性加重期、缓解期患者血浆MMP-9水平与FEV1.0%占正常预计值均呈负相关(r=-0.669,P<0.05;r=-0.537,P<0.05)。结论:IL-17与MMP- 9参与了慢性阻塞性肺疾病的发生发展过程,IL-17、MMP-9的检测对于慢性阻塞性肺疾病患者诊断治疗有重要意义。     

慢性阻塞性肺疾病急性加重期患者的炎性因子水平及糖代谢状态

目的了解AECOPD(慢性阻塞性肺疾病急性加重期)患者炎性因子水平,探讨其糖代谢状态。方法选取AECOPD患者24例,将其作为本研究的实验组,选择同时期24例COPD(慢性阻塞性肺疾病)稳定期患者及24例身体健康者作为本研究的对照组,监测各组研究对象的炎性因子水平及糖代谢水平。结果实验组患者hs-CRP、TNF-α、IL-6和LEP水平分别为(149.21±11.65)mg/L、(32.14±7.56)ng/L、(40.21±5.62)ng/L、(28.45±6.51)μg/L,FBG、2h PBG、HOMA-IR分别为(7.22±2.14)mmol/L、(8.01±2.55)mmol/L、(2.25±0.41),以上数据与对照组比较,差异有统计学意义(P<0.05)。结论 AECOPD患者存在胰岛素抵抗,其血清炎性因子水平显著高于COPD稳定期患者及身体健康者。     

Interaction of estrone and estradiol with DNA and protein of liver and kidney in rat and hamster in vivo and in vitro

[6,7-³H] Estrone (E) and [6,7-³H]estradiol-17 (E₂) have been synthesized by reduction of 6-dehydroestrone and 6-dehydroestradiol with tritium gas. Tritiated E and E₂ were administered by oral gavage to female rats and to male and female hamsters on a dose level of about 300 g/kg (54 mCi/kg). After 8 h, the liver was excised from the rats; liver and kidneys were taken from the hamsters. DNA was purified either directly from an organ homogenate or via chromatin. The radioactivity in the DNA was expressed in the units of the Covalent Binding Index, CBI = (mol chemical bound per mol DNA-P)/(mmol chemical administered per kg b.w.). Rat liver DNA isolated via chromatin exhibited the very low values of 0.08 and 0.09 for E and E₂, respectively. The respective figures in hamster liver were 0.08 and 0.11 in females and 0.21 and 0.18 in the males. DNA isolated from the kidney revealed a detectable radioactivity only in the female, with values of 0.03 and 0.05 for E and E₂, respectively. The values for male hamster kidney were < 0.01 for both hormones. The minute radioactivity detectable in the DNA samples does not represent covalent binding to DNA, however, as indicated by two sets of control experiments. (A) Analysis by HPLC of the nucleosides prepared by enzyme digest of liver DNA isolated directly or via chromatin did not reveal any consistent peak which could have been attributed to a nucleoside-steroid adduct. (B) All DNA radioactivity could be due to protein contaminations, because the specific activity of chromatin protein was determined to be more than 3,000 times higher than of DNA. The high affinity of the hormone to protein was also demonstrated by in vitro incubations, where it could be shown that the specific activity of DNA and protein was essentially proportional to the concentration of radiolabelled hormone in the organ homogenate, regardless of whether the animal was treated or whether the hormone was added in vitro to the homogenate.Carcinogens acting by covalent DNA binding can be classified according to potency on the basis of the Covalent Binding Index. Values of 10³–10⁴ have been found for potent, 10² for moderate, and 1–10 for weak carcinogens. Since estrone is moderately carcinogenic for the kidney of the male hamster, a CBI of about 100 would be expected. The actually measured limit of detection of 0.01 places covalent DNA binding among the highly unlikely mechanisms of action. Similar considerations can be made for the liver where any true covalent DNA binding must be below a level of 0.01. It is concluded that an observable tumor induction by estrone or estradiol is unlikely to be due to DNA binding.Paper presented at the Satellite Symposium of the European Society of Toxicology, Rome, March 29, 1983     

Penetration and action of edoxudine in vitro and in vivo

The penetration of 5-ethyl-2'-deoxyuridine (edoxudine, Aedurid) from gel base with and without the addition of urea and other adjuvant has been studied in an in vitro model using guinea pig skin. The formulation of 3% edoxudine gel with 5% urea showed the best results. In vivo experiments on hairless mice infected intracutaneously with herpes simplex virus type 1 also showed this formulation's good efficacy as compared to other formulations.     

Extraction and determination of prednisolone in drugs and excipients in ointments and creams and the uniformity of distribution in prednisolone ointment

For the purpose of measuring the contents of prednisolone in low concentrated ointments and creams an instruction was elaborated that includes several steps of extraction, in the resulting solution of which the assay of the steroid by Blue Tetrazolium reaction will be done. The procedure permits the determination of prednisolone in presence of most of usual ingredients of ointment bases except wool alcohols. Also no influence is given by some remedies combined with prednisolone for topical application except coal tar solution. The results confirm a correct reflection of the steroid contents declared respectively the recovery of the steroid added to various ointment bases. Introducing discussion to content uniformity concerning low concentrated ointments is made, and some deviations are shown.     

Mechanisms of antiplatelet and antithrombotic activity of midazolam in in vitro and in vivo studies

Dopamine regulates various physiological functions in the central nervous system and the periphery. Dysfunction of the dopamine system is implicated in a wide variety of disorders and behaviors including schizophrenia, addiction, and attention-deficit hyperactivity disorder. Medications that modulate dopamine signaling have therapeutic efficacy on the treatment of these disorders. However, the causes of these disorders and the role of dopamine are still unclear. Studying the dopamine system in a model organism, such as Caenorhabditis elegans, allows the genetic analysis in a simple and well-described nervous system, which may provide new insight into the molecular mechanisms of dopamine signaling. In this review, we summarize recent findings on pharmacological and biochemical properties of the C. elegans dopamine receptors and their physiological role in the control of behavior.     

Comparative in vivo and in vitro studies of phenytoin protein binding and in vitro lipolysis in plasma of pregnant and nonpregnant rats

This investigation was designed to determine the cause of the changes in drug protein binding that occur in rat plasma, particularly in plasma from pregnant animals, during in vitro drug-protein binding measurements. In vivo estimates of phenytoin binding in plasma were obtained from steady-state CSF-plasma concentration ratios in pregnant and nonpregnant rats. Immediate ultrafiltration of heparin- or EDTA-anticoagulated plasma yielded phenytoin free fraction values that were in good agreement with in vivo estimates for nonpregnant rats but that were about one-third higher than in vivo estimates for pregnant animals. In vitro free fraction values tended to increase during incubation of plasma and/or during equilibrium dialysis. The concentrations of the four major endogenous free fatty acids were similar in plasma of pregnant and nonpregnant rats if determined immediately after blood collection. Six hours of incubation at 37 degrees C caused fatty acid concentrations to increase about fivefold and twofold in heparin-anticoagulated plasma from pregnant and nonpregnant animals, respectively. The corresponding increases in EDTA-anticoagulated plasma were only about twofold and 1.14-fold, respectively. These changes were associated with decreased plasma protein binding of phenytoin. The in vivo differences between pregnant and nonpregnant rats with respect to phenytoin binding in plasma are not due to differences in fatty acid concentrations, but the in vitro differences are due primarily to corresponding differences in free fatty acid concentrations if extensive in vitro lipolysis occurs.     

Comparison of in vitro and in vivo developmental toxicity and pharmacokinetics of phenytoin in the rat

The rat whole embryo culture was compared to an in vivo experiment with regard to embryotoxicity as well as exposure characteristics, using phenytoin as a model compound. Intra-embryonic concentrations and their embryotoxic effects were determined on gestation day 11 after in vitro administration of 50-150 microg/ml or in vivo gavage of 500-1500 mg/kg body-weight on gestation day 10. In addition, exposure kinetics were studied in vivo after a single oral dose on gestation day 10, and developmental defects on gestation day 21 were scored. The embryotoxic effects observed on gestation day 11 were more pronounced after in vitro exposure in comparison to in vivo exposure at similar intra-embryonic concentrations. Exposure of phenytoin on gestation day 10 in vitro via the culture medium resulted in general embryotoxicity on gestation day 11, whereas in vivo effects as determined on gestation day 11 were minimal. Plasma concentrations of phenytoin increased and plateaued around 35 microg/ml during the 48 hr monitoring period. Plasma concentration curves and pharmacokinetic parameters did not show remarkable differences between the dose groups, indicating that absorption is the limiting factor at the dose range used. Although the developmental effects were minimal as observed in vivo on gestation day 11, specific malformations (defects encompassing the urogenital. craniofacial and skeletal systems) were observed on gestation day 21. These findings show that with similar intra-embryonic concentrations of phenytoin the embryotoxicity in rat whole embryo culture was not comparable with the in vivo embryotoxicity as determined on gestation day 11. This discrepancy may at least partly be explained by differences in exposure characteristics.     

Mathematical modelling of in situ and in vitro efflux of ciprofloxacin and grepafloxacin

The efflux process due to p-glycoprotein-like mechanisms of ciprofloxacin (CIP) and grepafloxacin (GRX) has been studied "in situ" in rats and "in vitro" in Caco-2 cells. The results were modelled by a curve fitting procedure which allowed the characterization of the passive (Pd) and carrier mediated parameters (Vm and Km) from the raw data without initial velocities estimation. CIP absorption in rat was characterized as a passive diffusion at the assayed concentrations. Although the involvement of an efflux transporter cannot be ruled out, its relevance in the transport of the fluoroquinolone is negligible. In GRX absorption, an efflux process is implicated and it is detected in both absorption models. GRX permeability depends on the intestinal segment, reflecting the previously reported different expression level of the efflux transporters along the gut in rat. A first attempt to correlate the "in vitro" and the "in situ" data has been done. The mathematical model has been constructed using very simplistic assumptions and it will require further refinement but, nevertheless, the results are promising and demonstrate that a good modelling approach helps to identify the system critical parameters and how the system behaviour change when the parameters are modified as it happens when we move from the "in vitro" to the "in situ" level. Predicted versus experimental permeability values show a good correlation, demonstrating that the relevance of the secretion process "in situ" in rat can be predicted from the "in vitro" cell results.     

Comparison of pulmonary and hepatic glucuronidation and sulphation of ethanol in rat and rabbit in vitro

1. Pulmonary and hepatic UDP-glucuronyltransferase and sulphotransferase activities in subcellular fractions from rats and rabbits were determined, comparing ethanol with known substrates for these enzymes.

2. No ethyl glucuronide formation was detected with either hepatic or pulmonary microsomal incubations.

3. Chromatographic, autoradiographic and scintillation counting analysis indicated that ethanol is sulphated by rat and rabbit pulmonary cytosol, although this activity was approx. 2–6% of that in liver.

4. Rat hepatic and pulmonary sulphotransferase activities with β-naphthol were approx. 13 and 60 times higher than with ethanol, respectively.

5. Rabbit hepatic and pulmonary sulphotransferase activities with both substrates were higher than those in rat.