急性百草枯中毒大鼠肺组织Toll样受体4和核因子-κB表达的变化

目的 观察急性百草枯(PQ)中毒大鼠肺组织中Toll样受体4(TLR4)和核因子-κB (NF-κB) mRNA表达的变化,探讨TLR4-NF-κB通路在急性PQ中毒肺损伤中的作用.方法 30只雄性SD大鼠随机分为2组:生理盐水(NS)对照组(6只,NS腹腔注射),PQ染毒组(24只,腹腔注射PQ溶液,20 mg/kg).PQ染毒组分别在染毒后6、24、48 h及72 h麻醉处死,NS对照组于处理后6h处死,进行肺组织HE染色,病理学观察,用实时定量PCR方法检测TLR4和NF-κB的mRNA表达情况,用ELISA方法测定肺组织中肿瘤坏死因子-α(TNF-α)、血清中IL-6含量.结果 PQ染毒组大鼠肺组织病理表现为早期充血水肿明显,大量炎性细胞浸润.与NS对照组相比PQ染毒组肺组织中TLR4和NF-κB mRNA的表达量、TNF-α、IL-6含量在各时间点均有不同程度升高,差异均具有统计学意义(P＜0.01).结论 大鼠急性PQ中毒后肺组织中TLR4和NF-κBmRNA表达量、TNF-α、IL-6含量明显上调,TLR4-NF-κB通路参与了PQ中毒大鼠肺损伤的早期病理生理过程.     

吡啡尼酮对百草枯中毒急性肺损伤的保护机制研究

目的 探讨吡啡尼酮(pirfenidone,PD)对百草枯(paraquat,PQ)中毒导致的ICR小鼠急性肺损伤(acute lung injury,ALI)的保护机制.方法 144只ICR小鼠(体质量23~27 g)分为空白对照组、中毒组、PD高剂量治疗组和PD低剂量治疗组.小鼠一次性腹腔注射30 mg/kg PQ溶液以制作急性肺损伤模型,染毒后立即分别予PD 30、70 mg/kg每日相同时间点灌胃1次,连续3 d.于2、6、12、24、48、72 h时间点取小鼠肺组织匀浆检测NF-κB、TNF-α、IL-1β含量,并分别观察各时间段的小鼠肺组织病理变化.结果 与空白对照组相比,中毒组NF-κB、TNF-α、IL-1β各时间点显著升高,持续至第3天仍未见明显下降;PD治疗组NF-κB亦升高但是24、48 h时低于中毒组,其中低剂量治疗组升高幅度小于高剂量组,但两者相比差异无统计学意义(P>0.05);病理检查可见小鼠PQ中毒肺泡腔有广泛的红细胞和浆液渗出,肺间质大量炎性细胞浸润以及肺泡间隔断裂,肺大疱形成;PD治疗组血管充血减轻,肺泡中炎性细胞和浆液渗出减少,肺大疱少见.结论 小鼠PQ中毒所致ALI可能和NF-κB、TNF-α、IL-1β的激活有关,吡啡尼酮对PQ中毒所致ICR小鼠ALI有治疗作用,其原理可能为抑制ALI时NF-κB、TNF-α、IL-1β的激活,从而减轻肺组织的炎症反应.     

百草枯中毒急性肺损伤TNF-α的表达及大黄保护作用的机制

目的 观察肿瘤坏死因子-α(TNF-α)在百草枯(PQ)中毒人鼠急性肺损伤中的表达,探讨大黄可能的作用机制.方法 PQ 50 mg/kg灌胃染毒制作PQ中毒Spragne-Dawley(SD)大鼠急性肺损伤模型.144只SD大鼠随机分为:空白对照组(A组,n=24),染毒组(B组,n=48),大黄组(C组,n=48)和空白十预组(D组,n=24).PQ(50 mg/kg)染毒,15 min内牛大黄(300 mg/kg·d)灌胃十预.血球记数板记数肺泡灌洗液巾中性粒细胞和细胞总数,Lowry法测定蛋白含量,计算中性粒细胞百分比及肺泡通透指数.取左肺HE染色脱察组织病理变化,免疫组织化学法检测TNF-α的表达.计量资料以均值±标准筹(x±s)表示,绀问单冈素方差分析,两两组间比较采用q检验,结果以P＜0.05为差异有统计学意义.结果 与A组相比,B组肺组织充血、水肿,炎性细胞浸润,少数见纤维化改变,肺泡灌洗液中性粒细胞比、蛋白含量及肺泡通透指数显著增高(P＜0.01);TNF-α染毒12 h表达明显增加,免疫组织化学评分(IHS)升高,1 d达高峰,差异有统计学意义(P＜0.05).之后维持较高水平,减轻趋势平缓.C组病理改变减轻,TNF-α亦呈阳性表达,IHS升高,但与B组相比,表达延迟,升幅减低,减弱趋势明显,差异有统计学意义(P＜0.05).结论 抑制TNF-α的表达,减轻炎症反应,可能是大黄减轻PQ中毒人鼠急性肺损伤的有效途径之一.     

孟鲁司特对百草枯所致大鼠肺损伤的治疗作用

目的 探讨孟鲁司特对百草枯(PQ)中毒所致大鼠肺组织中丙二醛(MDA)、超氧化物歧化酶(SOD)、肺湿/干质量比(W/D)和血清中肿瘤坏死因子(TNF-α)、白细胞介素-10(IL-10)、肺组织中核因子κB (NF-κBp65)及肺组织病理变化的影响.方法 取SD大鼠104只,随机(随机数字法)分为3组,PQ组40只、孟鲁司特组40只、对照组24只.PQ组和孟鲁司特组用百草枯一次性染毒,分别在不同处理后第1、3、5、7天时处死大鼠.观察肺组织中MDA和SOD含量、肺湿/干质量比(W/D)、血清TNF-α、IL-10含量及肺组织中NF-κBp65含量,并取肺组织制备标本分别在光镜和电镜下观察肺组织的病理改变.结果 PQ组第7天时肺组织中MDA含量、肺组织湿/干质量比、血清TNF-α和IL-10含量、肺组织中NF-κBp65含量明显高于对照组,SOD含量明显低于对照组,差异均具有统计学意义(P＜0.01).孟鲁司特组第7天时肺组织中MDA含量、肺组织湿/干质量比、血清TNF-α和IL-10含量、肺组织中NF-κBp65含量明显低于PQ组,SOD含量明显高于PQ组,差异均具有统计学意义(P＜0.05).光镜及电镜观察PQ组病理学改变为急性弥漫性肺损伤,表现为肺泡腔内出血、渗出、炎性细胞浸润,Ⅰ型和Ⅱ型上皮细胞坏死脱落;孟鲁司特组大鼠肺组织病理改变为局灶性肺泡少量炎性细胞浸润,Ⅰ型上皮细胞完整,Ⅱ型上皮细胞未见明显坏死.结论 孟鲁司特对百草枯中毒所致大鼠急性肺损伤具有一定的保护作用.     

百草枯中毒致大鼠肺组织损伤时氨溴索对肺组织Bcl-2/Bax的表达及细胞凋亡的影响

目的 探讨在百草枯(PQ)中毒所致大鼠急性肺损伤时氨溴索(AM)对肺组织Bcl-2/Bax的表达及细胞凋亡的影响.方法 44只大鼠随机分为4组:正常对照组(C组)6只、AM对照组(AM组)6只、急性肺损伤组(PQ组)16只和急性肺损伤+AM治疗组(PQ+AM组)16只.取肺组织苏木精-伊红(HE)染色来评价肺组织损伤情况;检测血清中肿瘤坏死因子α(TNF-α)水平;蛋白质印迹方法检测肺组织p38丝裂酶原激活蛋白激酶(MAPK)表达;肺组织Bcl-2、Bax免疫组化分析;TUNEL检测肺组织细胞凋亡.结果 C组和AM组大鼠的肺组织结构基本完整,PQ组肺组织损伤程度加重,PQ+AM组肺组织损伤程度较PQ组减轻.PQ组血清TNF-α水平、p38 MAPK和Bax蛋白表达、肺组织细胞凋亡均较C组和AM组显著增加(P＜0.05),PQ+AM组较PQ组均有降低(P＜0.05),而抗凋亡基因Bcl-2在AM干预后较PQ组升高(P＜0.05).结论 百草枯中毒导致了大鼠急性肺损伤,经氨溴索治疗后,通过调节p38 MAPK、Bcl-2和Bax蛋白的表达从而使肺组织细胞凋亡减少,从而有效地减轻了百草枯中毒所致的大鼠急性肺损伤.     

N-乙酰半胱氨酸对百草枯中毒大鼠肺组织细胞凋亡及Fas/FasL的影响

目的 探讨百草枯( paraquat,PQ)中毒所致大鼠急性肺损伤时N-乙酰半胱氨酸( N-acetylcysteine,NAC)对肺组织的细胞凋亡和Fa/FasL表达的影响.方法 将SD大鼠随机(随机数字法)分为对照组、PQ染毒组和NAC治疗组,每组15只.复制PQ染毒大鼠急性肺损伤模型,腹腔注入2％百草枯液( 25 mg/ kg);NAC治疗组为0.5h后对PQ染毒大鼠,再腹腔注射NAC (200 mg/kg)进行干预;对照组腹腔注射等量生理盐水.利用原位缺口末端标记(TUNEL)法检测肺组织细胞凋亡率,采用逆转录-聚合酶链反应(RT-PCR)和蛋白质印迹(Western blot)方法分别检测肺组织Fas/FasL mRNA和蛋白的表达.结果 PQ组和对照组相比细胞凋亡率和Fas/FasL系统表达差异均具有统计学意义(P＜0.05);NAC治疗组细胞凋亡率和fas/fasL表达明显降低,和PQ组相比差异均有统计学意义(P＜0.05).结论 NAC可能通过抑制Fas/FasL系统活化抑制百草枯中毒大鼠肺组织细胞凋亡.     

虎杖苷对百草枯中毒大鼠急性肺损伤的保护作用

目的:通过虎杖苷(PD)的干预,观察其对百草枯(PQ)中毒急性肺损伤的保护效果。方法:48只大鼠随机分4组:PQ组、PD治疗组、PD对照组和正常对照组。将PD溶液通过尾静脉注入大鼠体内,观察末次注射后第3、7天各组大鼠的肺干湿比、血浆中IL-1β、TNF-α、丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化酶(GSH-PX)的水平变化。结果:与PQ组相比,在末次注射后的第3、7天PD治疗组明显降低肺干湿比(P0.01)和炎性递质IL-1β、TNF-α的含量(P0.01),降低血浆中MDA的水平(P0.01)和升高SOD、GSH-PX的水平(P0.01)。PD对照组在各时段与正常对照组比较差异无统计学意义。结论:PD对PQ中毒急性肺损伤具有保护作用。     

甲泼尼龙联合环孢素A对百草枯中毒的防治

目的 在建立百草枯(paraquat,PQ)中毒致肺纤维化大鼠模型的基础上,探讨早期大剂量甲泼尼龙联合环孢素A治疗对PQ中毒大鼠肺组织病理变化、氧化一抗氧化指标和肺纤维化特异性指标的影响,以判断疗效.方法 (1)PQ中毒致肺纤维化大鼠模型的建立:40只雄性Wistar大鼠随机(随机数字法)分为5组,分别采用20 mg/kg,25 mg/kg,30 mg,/kg,35mg/kg和40 mg/kg5个PQ剂量水平进行染毒.计算各组大鼠的两周死亡率及观察肺组织病理形态学变化.以肺组织病理表现为纤维化、死亡率在可接受范围之内作为模型染毒剂量,并以生化指标验证.(2)甲泼尼龙联合环孢素A对PQ中毒大鼠肺纤维化的疗效观察:72只雄性Wistar大鼠随机分为正常对照组(8只)、模型组(16只)、药物干预组(48只)3组.正常对照组注射25 mg/kg生理盐水;其余组PQ 25 mg/kg染毒.药物干预组再随机分为3组(每组16只),分别于染毒后2 h,24 h,72 h三个时间点单次应用甲泼尼龙(90 mg/kg)联合环孢素A(22.5 mg/kg).染毒后7 d,14 d观察大鼠肺组织病理变化,采用碱水解法、黄嘌呤氧化酶法和硫代巴比妥酸法分别测定肺组织超氧化物歧化酶(SOD)、丙二醛(MDA)和羟脯氨酸(HPY)的含量.组间比较采用两因素析因设计的方差分析,组内比较采用单因素3水平设计的方差分析.结果 25 mg/kg为肺纤维化大鼠模型的PQ染毒剂量.与模型组比较,各药物干预组大鼠肺组织肺泡数量明显增多,成纤维细胞增生程度较轻,胶原及纤维含量较少.与模型组比较,各药物干预组大鼠肺组织SOD含最增加,HPY和NDA含量明显降低(P＜0.05或P＜0.01).与72 h药物干预组比较,2 h,24 h药物干预组大鼠肺组织成纤维细胞增生程度较轻,胶原、纤维较少,肺组织SOD含量明显升高(P＜0.05或P＜0.01),MDA含量明显降低(P＜0.01).结论 早期联合应用大剂量甲泼尼龙和环孢素A治疗PQ中毒大鼠,可以显著减轻PQ中毒所致的肺组织氧化损伤和肺纤维化程度,改善预后.     

依达拉奉对百草枯中毒大鼠急性肺损伤的保护作用

目的：探讨依达拉奉（edaravone）对百草枯（paraquat PQ）中毒致大鼠急性肺损伤的治疗作用及其可能的机制。方法：大鼠一次性腹腔内注射PQ 20 mg/kg,染毒同时及染毒后不同时间腹腔注射依达拉奉,在6个不同时间点观察其肺组织病理改变及肺组织匀浆中的丙二醛（MDA）含量及超氧化物歧化酶（SOD）的活力。结果：给予依达拉奉治疗后,肺泡壁充血、出血均明显减轻,MDA含量下降;SOD活力逐渐升高。结论：依达拉奉可减轻百草枯中毒后所致的弥漫性肺损伤,减轻氧自由基损伤,抑制脂质过氧化作用。依达拉奉可能成为治疗百草枯中毒的药物。     

褪黑素对急性百草枯中毒大鼠的治疗效果

目的 观察褪黑素(MT)对急性百草枯(PQ)中毒大鼠的治疗效果.方法 选择成年SD大鼠54只,随机分为正常对照组、染毒组和治疗组(每组18只).正常对照组用生理盐水灌胃,染毒组用PQ一次性灌胃(50 mg/kg)染毒,治疗组在染毒后随即腹腔注入MT 10 mg/kg,1次/d.分别于1d、3 d和7 d测定3组大鼠血清中丙二醛(MDA)含量及超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活力,并观察大鼠中毒表现及肺组织病理改变.结果 PQ染毒后大鼠血清中MDA含量显著高于对照组(P＜0.01);而血清SOD及GSH-Px活力明显低于对照组(P＜0.05).与染毒组比较,治疗组大鼠血清MDA含量下降;GSH-Px和SOD活力逐渐升高,差异具有统计学意义(P＜0.05).其中毒表现及肺组织病理学改变均明显减轻.结论 MT可减轻急性PQ中毒引起的脂质过氧化反应,改善大鼠的中毒症状.     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

Clinical Pharmacokinetics of Morphine

Morphine, the most widely used mu-opioid analgesic for acute and chronic pain, is the standard against which new analgesics are measured. A thorough understanding of the pharmacokinetics of morphine is required in order to safely and effectively use this analgesic in a wide variety of patients with different levels of organ function. A MEDLINE search was conducted to identify literature published between 1966 and January 2002 relevant to the pharmacokinetics of morphine. These publications were reviewed and the literature summarized regarding unique and clinically important elements of morphine disposition relative to its parenteral administration (including intravenous, intramuscular, subcutaneous, epidural and intrathecal administration), absorption profile (immediate release, controlled release, and sublingual/buccal, and rectal administration), distribution, and its metabolism/ excretion. Special populations, including infants, elderly, and those with renal/liver failure, have a unique morphine pharmacokinetic profile that must be taken into account in order to maximize analgesic efficacy and reduce the risk of adverse events.