氯沙坦对糖尿病大鼠肾小管间质P38MAPK表达的影响

【目的】探讨P38丝裂原活化的蛋白激酶（P38MAPK）与糖尿病肾病（DN）肾小管间质病变的关系,及氯沙坦对其的影响。【方法】雄性Wistar大鼠,随机分为正常对照组和模型组,后者经STZ诱导糖尿病模型成功后再随机分为糖尿病模型组和氯沙坦干预组。8周后检测各组大鼠24 h尿蛋白、血肌酐;留取肾组织行HE和MASSON染色,观察肾小管间质损伤指数、肾间质胶原面积;免疫组化检测肾小管间质磷酸化P38MAPK以及TGFβ1表达,并做半定量分析。【结果】①与对照组相比,糖尿病模型组大鼠尿蛋白排泄量、肾小管间质损伤指数和肾间质胶原面积明显增加（P〈0.01）;②糖尿病组大鼠肾小管间质磷酸化P38MAPK、TGFβ1表达均显著高于对照组（P〈0.01）;③氯沙坦组尿蛋白排泄量、肾小管间质损伤程度较糖尿病组减轻,肾小管间质磷酸化P38MAPK、TGFβ1表达较糖尿病组显著下调（P〈0.01）。【结论】糖尿病肾病小管间质病变的病理过程中存在P38MAPK的活化;氯沙坦可阻抑糖尿病大鼠肾小管间质P38MAPK活化,下调TGFβ1表达而发挥肾脏保护作用。     

冬虫夏草对糖尿病大鼠肾小管上皮细胞ILK表达的影响

[目的]观察糖尿病大鼠肾小管上皮细胞整合素连接激酶(ILK)的表达及冬虫夏草对其表达的影响.[方法]雄性Wistar大鼠随机分为3组:正常对照组(N组,n=12)、糖尿病模型组(D组,n=12)、糖尿病冬虫夏草干预组[C组,n=12,冬虫夏草1000 mg/(kg·d)灌胃].成模后第8周末及16周末各组分别处死6只大鼠,测定24 h尿蛋白排泄量、血肌酐;HE及MASSON染色法观察肾脏病理改变;免疫组织化学法检测ILK、E钙粘蛋白(E-cad)、α平滑肌肌动蛋白(α-SMA)及转化生长因子β1(TGF-β1)的表达.[结果]①与N组比较,D组大鼠肾小管间质损伤指数、肾间质胶原面积明显增加(P<0.01).②D组大鼠肾小管上皮细胞E-cad阳性表达显著低于N组,TGF-β1、ILK和α-SMA阳性表达均显著高于N组;E-cad表达和TGF-β1表达呈负相关(rs=-0.60,P<0.05);ILK、α-SMA表达和TGF-β1表达呈正相关(rs=0.88,P<0.01;rs=0.91,P<0.05).③C组大鼠肾小管间质损伤指数、肾闻质胶原面积较D组明显减弱,其肾小管上皮细胞的E-cad的表达较D组明显增加,TGF-β1、ILK和α-SMA表达较D组均明显减弱(P<0.01).[结论]冬虫夏草能通过下调ILK表达发挥肾脏保护作用.     

姜黄素对单侧输尿管梗阻大鼠肾小管上皮细胞转分化影响的研究

目的:探讨姜黄素对单侧输尿管梗阻(UUO)大鼠肾小管上皮细胞转分化的作用。方法:采用UUO致肾间质纤维化大鼠模型。将24只大鼠随机均分为假手术组、模型组和姜黄素组。从制模后2 d起,姜黄素组给予100 mg.kg-1.d-1姜黄素腹腔注射。术后4周心脏穿刺抽血,测定各组大鼠血清尿素氮(BUN)和血肌酐(SCr)值。处死大鼠,用苏木素-伊红(HE)、Masson染色评定肾小管间质纤维化程度;用免疫组化方法检测肾组织内转化生长因子-β1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA)、波形蛋白(Vimentin)的蛋白表达部位及表达水平。结果:与假手术组比较,模型组大鼠BUN水平显著增加(P<0.01),肾间质纤维组织相对面积显著扩大(P<0.01),肾组织内TGF-β1、α-SMA和Vimentin的蛋白表达均显著上调(P均<0.01)。姜黄素干预后,上述上调指标都被显著抑制(P<0.05或P<0.01)。结论:姜黄素可能通过抑制UUO大鼠肾小管上皮细胞转分化而减轻肾间质纤维化。     

氯沙坦对梗阻性肾病大鼠肾间质固有细胞的作用

目的研究氯沙坦对梗阻性肾病大鼠肾间质固有细胞的作用,寻找可能的临床抑制肾间质纤维化的方法。方法采用单侧输尿管结扎(UUO)模型,治疗组于造模当日至造模后14天给予科素亚[16mg(kg·d)]灌胃,另设假手术组及手术组作为对照。应用免疫组织化学方法检测肾间质TGF-β的表达,组化双染色观察α-SMA、E-钙粘素的表达。激光共聚焦显微镜观察间质小管区α-SMA表达。结果手术组两周时出现近端肾小管区TGF-β表达明显增高(P<0．01),伴α-SMA表达增高(P<0．01),E-钙粘素表达下降(P<0．05),部分肾小管细胞中可见α-SMA及E-钙粘素同时表达;治疗组与手术组相比TGF-β、α-SMA的表达明显下降(P<0．05),而E-钙粘素的表达上调(P<0．05)。共聚焦显微镜下见部分小管基底膜损伤,上皮细胞表达α-SMA。结论氯沙坦可通过抑制肾间质固有细胞转分化过程的进展,从而对肾间质纤维化具有治疗作用。     

霉酚酸酯对糖尿病大鼠肾组织中TGF-β1、p-Smad2/3表达的影响

【目的】观察霉酚酸酯(MMF)对糖尿病大鼠肾组织中转化生长因子-β1(TGF-β1),p-Smad2/3表达的影响,探讨MMF对糖尿病肾病的保护作用及其机制。【方法】36只雄性SD大鼠随机分为正常对照组,糖尿病模型组和MMF治疗组,行单侧肾脏切除术,以链脲佐菌素(STZ)腹腔内注射建立糖尿病大鼠模型,药物干预后第4,12周每组处死6只大鼠,测24h尿蛋白定量,HE,Masson染色观察肾脏组织学改变;免疫组织化学方法检测TGF-β1,p-Smad2/3在肾组织中的表达。【结果】正常对照组有少量TGF-β1和p-Smad2/3表达,模型组大鼠24h尿蛋白排泄量增多(P<0.05),系膜区基质增多,TGF-β1和p-Smad2/3表达均明显增强(P<0.05);MMF治疗组24h尿蛋白排泄量显著下降(P<0.05),肾组织TGF-β1和p-Smad2/3表达均有减少(P<0.05)。【结论】在糖尿病大鼠模型中,MMF能下调TGF-β1,p-Smad2/3的表达,减少蛋白尿,延缓肾脏纤维化的进展,从而达到对糖尿病肾病的保护作用。     

肾康注射液对单侧输尿管梗阻大鼠肾间质纤维化的影响

目的研究肾康注射液对梗阻性肾病大鼠肾小管间质纤维化的防治作用。方法采用单侧输尿管梗阻(UUO)诱导肾间质纤维化的动物模型,以血管紧张素Ⅱ受体拮抗剂(ARB)作为阳性对照,将大鼠随机分为:模型组(UUO)、肾康组、缬沙坦组,术后第14天处死大鼠,收集血清测定肌酐、尿素氮水平,肾组织用HE染色及免疫组化半定量检测各组肾间质的α-平滑肌肌动蛋白(α-SMA)、转化生长因子-β1(TGF-β1)的表达。结果肾康组、缬沙坦组的肾小管间质TGF-β1、α-SMA的表达均明显低于UUO组;两治疗组组间比较,肾康组对TGF-β1、α-SMA表达的抑制作用同于缬沙坦组。结论中药肾康可减轻肾间质纤维化。     

绞股蓝总皂甙对单侧输尿管结扎大鼠肾组织结缔组织生长因子表达的影响

目的:研究绞股蓝总皂甙(GPs)对单侧输尿管结扎(UUO)大鼠肾组织结缔组织生长因子(CTGF)表达及肾间质纤维化的影响。方法:采用UUO大鼠模型,将大鼠随机分为4组:假手术组、模型组、GPs组、缬沙坦组。假手术组和模型组仅给予标准饲料30g,GPs组和缬沙坦组于术前3d至术后9d每天分别给予GPs200mg/(kg·d)、缬沙坦24mg/(kg·d)灌胃,第9天处死各组大鼠。免疫组化法检测各组肾组织CTGF、转换生长因子β1(TGF-β1)和α-平滑肌肌动蛋白(α-SMA)的表达;RT-PCR方法检测各组CTGFmRNA含量;Masson染色评定各组肾小管间质损害程度。结果:模型组CTGF、TGF-β1、α-SMA的表达及肾小管间质损伤指数明显高于假手术组(P<0.01),而GPs组和缬沙坦组各项指标明显低于模型组(P<0.01);GPs组与缬沙坦组差异无显著性(P>0.05)。各项指标作相关分析,CTGF与肾小管间质损伤指数(r=0.756,P<0.01)、TGF-β1(r=0.879,P<0.01)、α-SMA(r=0.892,P<0.01)为正相关关系。结论:GPs可以抑制肾纤维化时CTGF表达,从而...     

缬沙坦及苯那普利对5/6肾切除大鼠肾小管间质的影响

目的 观察并比较缬沙坦及苯那普利对5/6肾切除大鼠肾小管间质损伤的改善作用。方法 SD雄性大鼠30只,通过5/6肾切除法制造慢性肾功能衰竭模型,术后2周随机分为模型组、缬沙坦组及苯那普利组,并设假手术组作为对照。术后第6周末测定各组大鼠血清肌酐(Scr)及尿素氮(BUN)浓度,此后处死大鼠,取出肾组织进行病理组织形态学观察,并采用免疫组织化学方法检测肾小管间质转化生长因子β1(TGF-β1)、Ⅰ型胶原及Ⅲ型胶原表达。结果 同模型组相比,两治疗组肾小管间质损伤指数明显降低(P<0.01);免疫组化染色显示,两治疗组肾小管间质转化生长因子β1(TGF-β1)、Ⅰ型胶原及Ⅲ型胶原表达均较模型组下降(P均<0.01)。结论 缬沙坦及苯那普利对慢性肾功能衰竭大鼠肾小管间质损伤具有保护作用。     

活性维生素D_3对大鼠肾小管间质纤维化的影响及其机制研究

目的:观察活性维生素D_3对大鼠肾小管间质纤维化的影响及其可能机制。方法:将40只雄性SD大鼠随机分为4组:假手术组(Sham组)、模型组(UUO组)、UUO+低剂量活性维生素D_3组(LV组)、UUO+大剂量活性维生素D_3组(HV组),每组10只。采用单侧(左)输尿管结扎法建立梗阻性肾小管间质纤维化大鼠模型。Sham组只游离左侧输尿管而不结扎。LV组与HV组分别予以0.03μg/(kg·d)、0.06μg/(kg·d)活性维生素D_3(溶于花生油)腹腔注射,Sham组和UUO组均予以等体积花生油腹腔注射。术后14 d处死大鼠,采集血、肾脏标本,并检测血清钙、磷、肌酐(SCr)、甲状旁腺激素(PTH)。制作肾脏病理组织切片,行H-E、Masson染色,在光镜下观察肾小管间质损伤及纤维化情况。采用免疫组织化学法检测肾小管间质中α平滑肌肌动蛋白(α-SMA)、E钙黏蛋白(E-cadherin)与转化生长因子β(TGF-β)的表达。结果:与UUO组相比,LV组和HV组SCr水平[(39.0±1.83)μmol/L、(36.0±2.11)μmol/L比(43.1±5.55)μmol/L]、肾小管间质纤维化指数(2.00±0.12、1.70±0.10比2.80±0.11)、α-SMA表达(0.22±0.02、0.20±0.03比0.24±0.02)、TGF-β表达(0.26±0.03、0.25±0.03比0.32±0.04)均显著下降(P0.05),E-cadherin表达(0.30±0.08、0.34±0.11比0.22±0.07)明显升高。与LV组相比,HV组SCr水平肾间质纤维化指数、肾间质损伤指数、α-SMA表达、TGF-β表达明显下降(P0.05),E-cadherin表达上升(P0.05)。相关性分析显示,TGF-β、α-SMA表达与肾间质纤维化指数正相关,E-cadherin表达与肾间质纤维化指数负相关;TGF-β表达与α-SMA表达正相关,E-cadherin与TGF-β负相关;α-SMA表达与E-cadherin表达负相关。结论:活性维生素D_3可改善UUO大鼠肾小管间质纤维化,大剂量活性维生素D_3改善作用优于小剂量,其机制可能是:通过抑制TGF-β的过度表达从而抑制UUO大鼠肾小管上皮细胞-肌成纤维细胞转分化进而改善肾小管间质纤维化。     

不同剂量氯沙坦对防治肾间质纤维化效果的影响

目的：观察血管紧张素Ⅱ受体拮抗剂（ARBs）氯沙坦对大鼠单侧输尿管梗阻（UUO）模型肾间质纤维化的影响．探讨超大剂量能否优于常规剂量起到更多的肾脏保护作用：方法：建立大鼠UUO模型，术后3d分为常规剂量治疗组、超大剂量治疗组、UUO组和假手术组。药物干预组分别每天给予氯沙坦50mg／kg、氯沙坦500mg／kg灌胃，假手术组及UUO组每天给予同体积生理盐水灌胃。观察模型第7、14和21天鼠尾袖带血压（TCP）、24h尿蛋白、肾小管损害程度、肾间质纤维化程度、肾间质巨噬细胞数和转化生长因子-β1（TGF-β1）mRNA的表达。结果：随着梗阻时间延长．UUO组TCP逐渐增高、24h尿蛋白、肾间质纤维化程度、肾小管损害程度及肾间质巨噬细胞浸润显著增加，TGF-β1 mRNA含量明显增加，与其余各组相比差异有显著性（P〈0.05）。同时，超大剂量氯沙坦相对于常规剂量，能更有效地控制血压、减少蛋白尿、减轻肾小管损害和肾间质纤维化、减少肾间质单核巨噬细胞浸润，显著抑制TGF-β1 mRNA表达。结论：超大剂量氯沙坦在UUO大鼠模型中较常规剂量起到了更多的肾脏保护作用.     

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.     

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.     

Evidence-Based Pain Management and Palliative Care in Issue Four for 2009 of The Cochrane Library

ABSTRACT

The Cochrane Library of Systematic Reviews is published quarterly. Issue 4 for 2009 contains 4027 complete reviews, 1906 protocols for reviews in production, and 11447 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 600,000 randomized controlled trials, and 12,200 cited papers in the Cochrane methodology register. The health technology assessment database contains over 7500 citations. This edition of the Library contains 90 new reviews, of which 19 have potential relevance for practitioners in pain and palliative medicine.     

Molecular characterization of virulence and antimicrobial resistance profile of Shigella species isolated from children with moderate to severe diarrhea in northeastern Brazil

Molecular characterization of virulence and antimicrobial resistance profiles were determined for Shigella species isolated from children with diarrhea in Fortaleza, Brazil. Fecal specimens were collected along with socioeconomic and clinical data from children with moderate to severe diarrhea requiring emergency care. Shigella spp. were isolated by standard microbiological techniques, and we developed 4 multiplex polymerase chain reaction assays to detect 16 virulence-related genes (VRGs). Antimicrobial susceptibility tests were performed using disk diffusion assays. S. flexneri and S. sonnei were the predominant serogroups. S. flexneri was associated with low monthly incomes; more severe disease; higher number of VRGs; and presence of pic, set, and sepA genes. The SepA gene was associated with more intense abdominal pain. S. flexneri was correlated with resistance to ampicillin and chloramphenicol, whereas S. sonnei was associated with resistance to azithromycin. Strains harboring higher numbers of VRGs were associated with resistance to more antimicrobials. We highlight the correlation between presence of S. flexneri and sepA, and increased virulence and suggest a link to socioeconomic change in northeastern Brazil. Additionally, antimicrobial resistance was associated with serogroup specificity in Shigella spp. and increased bacterial VRGs.     

护理干预对面部中重度寻常型痤疮的临床疗效影响分析

目的研究护理干预对面部中重度寻常型痤疮的临床疗效影响。方法选取本院在2014年4月~2016年7月诊治的136例面部中重度寻常型痤疮患者,随机分为研究组与对照组,每组68例;所有患者均依据其情况给予对应的治疗,其中对照组在治疗期间给予常规护理,研究组在对照组的基础上再给予综合性护理干预,比较两组的治疗效果及护理满意度情况等。结果患者在接受治疗和护理后,研究组中度与重度患者的治疗效果较对照组均明显提高(P0.05),研究组护理满意度较对照组明显增高(P0.05)。结论对面部中重度寻常型痤疮患者在其治疗期间给予综合性护理干预,具有良好的效果。