肾移植后排斥与感染中细胞免疫功能的监测

背景：Cylex ImmuKnow检测方法是惟一得到FDA认可的检测移植受者细胞免疫功能的方法, 它直接反映细胞免疫的功能,具有灵敏度高、特异性强,结果量化等优点。 目的：通过对肾移植后患者监测细胞免疫功能iATP值(intracellular adenosine triphosphatei),分析细胞免疫功能与肾移植术后排斥或感染的关系。 方法：140例肾移植受者采用ImmuKnowTM-Cylex®方法检测细胞免疫功能,收集数据结合患者临床状态分为排斥组18例,感染组35例与稳定组87例,同时收集61份健康人群血样检测细胞免疫功能数据作对照。分析细胞免疫功能与肾移植患者移植后发生排斥与感染的关系。 结果与结论：细胞免疫功能iATP值检测结果显示,感染组患者有71.4%(n=25)分布在低免疫区,同比对照组、稳定组与排斥组比例明显增高(P < 0.05)。感染组iATP值显著低于其他3组。说明感染与细胞免疫功能低下两者具有明显的相关性,细胞免疫功能测定对监测肾移植后感染具有显著意义。提示ImmuKnowTM-Cylex®方法测定细胞免疫功能为肾移植后并发感染的诊断与治疗提供可靠客观依据,但与肾移植后排斥反应的发生未见明显的相关性,有待于大样本的实验证实。     

运动诱导骨骼肌线粒体生成中沉默信息调节因子1的作用

BACKGROUND:Silent information regulator factor-1 is an energy metabolism regulator newly received attention in sports science, which playing roles in skeletal exercise-induced muscle mitochondrial biogenesis with other regulatory factors. OBJECTIVE:To review the effect and mechanism of silent information regulator factor-1 on skeletal muscle mitochondrial biogenesis in exercise. METHODS: The PubMed database and Highwire database were retrieved with computer for the articles on exercise, silent information regulator factor-1 and skeletal muscle mitochondrial biogenesis from January 2000 to January 2013 with the key words of “SIRT1, AMPK, PGC-1α, mitochondrial biogenesis, skeletal muscle, exercise” in English. After primary search, the articles about the association between silent information regulator factor-1 and skeletal muscle mitochondrial biogenesis in exercise were selected. Articles on repeated experiment were excluded. RESULTS AND CONCLUSION:Totally 165 relevant articles were selected, and articles on repetitive research were excluded, so finaly 62 articles were included. As a NAD+-depended deacetylase, silent information regulator factor-1 induced skeletal muscle mitochondrial biogenesis by up-regulated peroxisome proliferator-activated receptor coactivator after activated during exercise. The molecular mechanism involved adenosine monophosphate-activated protein kinase and hypoxia-inducible factor 2α. In recent years, the effect of silent information regulator factor-1 on skeletal muscle mitochondrial biogenesis was doubt, the researchers though that silent information regulator factor-1 was not required for exercise-induced muscle mitochondrial biogenesis.Silent information regulator factor-1 plays an important role in exercise-induced muscle mitochondrial biogenesis. But protein and activity detection methods are different in experimental results.     

腺苷A1受体激动剂预处理对兔心肌缺血再灌注损伤的延迟保护作用

【目的】探讨腺苷A1受体激动剂（2-氯环戊腺苷,CCPA）预处理对兔心肌缺血再灌注损伤的延迟保护作用。【方法】30只健康新西兰雄性大白兔随机分成3组：假手术组（C组）、缺血再灌注组（I／R组）、CC—PA组（P组）,每组10只。C组仅行左冠脉套线而不阻断160min,I／R组行左冠脉阻断40min,再灌注120min,P组在静注CCPA 0．1mg／kg 24h后,处理同I／R组。各组分别于左冠前降支阻断前20min（T1）、左冠前降支阻断20min（T2）、左冠前降支阻断40min（T3）、心肌再灌注1h（T4）、心肌再灌注2h（T5）五个时点抽取颈内动脉血测定血清中肌钙蛋白Ⅰ（cTnI）含量。再灌注120min后,测心肌超氧化物歧化酶（SOD）活性、丙二醛（MDA）含量和心梗面积,电镜下观察细胞超微结构变化。【结果】与I／R组比,P组cTnI和MDA降低（P〈0．05）,SOD增高（P〈0．05）,心肌梗死面积减少（P〈0．05）,细胞结构损伤减轻。【结论】CCPA延迟预处理对兔心肌缺血再灌注损伤有保护作用。     

Ginsenoside Rb1 promotes PC12 cell cycle kinetics through an adenylate cyclase–dependent protein kinase A pathway

Ginsenoside Rb1 (G-Rb1), a constituent of ginseng, bears various beneficial effects on neuroendocrine cells. Previous studies have indicated that G-Rb1 can enhance glutamate release in undifferentiated and differentiated PC12 cells via the protein kinase A (PKA)–dependent signaling pathway. We hypothesized that G-Rb1 stimulates rat adrenomedullary chromaffin cell line PC12 (PC12 cells) proliferation and mitosis by promoting the cell cycle at all regulatory points. This mechanism is partly mediated via the adenylate cyclase–dependent PKA signaling pathway. In the present study, we investigated the mechanism by which G-Rb1 promotes cell cycle kinetics from the PC12 cells. The cell cycle kinetics of these cells were determined using flow cytometric DNA analysis. Analysis of the PC12 cell cycle revealed that G-Rb1 may affect all phases of the cell cycle and accelerate cell cycle kinetics by stimulating G0G1 phase transiting to S and G2M phases. The cell cycle kinetics were decreased by coincubating with the adenylate cyclase inhibitor SQ22536. Compared with the G-Rb1–treated group, the PKA inhibitor H89 produced a marked decrease in the G-Rb1–stimulated cell cycle kinetics by inhibiting G0G1 phase from transiting to the S phase. These results support the position that G-Rb1 exerts a stimulatory effect on cell cycle kinetics to promote PC12 cell proliferation. The result also suggests that the division rate is mediated via the adenylate cyclase–dependent PKA signaling pathway.     

降钙素原与腺苷脱氨酶检测在小儿脑膜炎中的应用价值 FREE

目的探讨血清降钙素原（PCT）和脑脊液（CSF）腺苷脱氨酶（ADA）检测在小儿脑膜炎临床鉴别诊断中的应用价值。方法采用固相免疫色谱法测定化脓性脑膜炎（化脑组,33例）、结核性脑膜炎（结脑组,24例）、病毒性脑膜炎（病脑组,38例）及对照组（同期住院的癫痫患儿）血清PCT水平,酶动力学法检测CSF中ADA活性。结果化脑组患儿血清PCT全部阳性,阳性率达100.00%,与其余各组比较,差异均有显著性（P＜0.001）;病脑组中仅1例（2.63%）患儿血清PCT阳性;结脑组和对照组血清PCT全部阴性。化脑组和结脑组CSF ADA活性明显高于病脑组和对照组（P＜0.001）;结脑组与化脑组CSF ADA活性差异有高度显著性（P＜0.001）,且结脑组CSF ADA阳性率达83.33%（20/24）,而化脑组CSF ADA活性水平均在正常范围内。 结论血清PCT水平和CSF ADA活性的同时检测有助于小儿脑膜炎的临床鉴别诊断。     

腺苷A3对失血性休克血管反应性的调节作用

目的探讨腺苷A3受体（adenosine A3 receptor,A3AR）对失血性休克大鼠肠系膜上动脉对α受体激动剂（去甲肾上腺素）收缩反应性的调控作用,并初步探讨钾通道在其中的可能作用。方法建立失血性休克（40mmHg）诱导大鼠肠系膜上动脉对去甲肾上腺素（norepinephrine,NE）低反应性模型。大鼠肠系膜上动脉血管对NE诱导的收缩反应性采用离体小血管张力测定仪检测。结果结果显示,在大鼠失血性休克后0～4h,其肠系膜上动脉1级分支血管对由NE诱导的收缩反应性呈现＂双向性＂变化;A3AR激动剂（IB-MECA）可明显改善失血性休克大鼠肠系膜上动脉1级分支由NE诱导的收缩反应性,且该作用可被A3AR阻断剂（MRS1523）所拮抗;此外,大电导钙激活钾通道（BKCa）开放剂NS1619可部分拮抗IB-MECA休克血管反应性的恢复作用;但ATP依赖钾通道（KATP）开放剂吡哪地尔对IB-MECA对休克血管反应性的恢复作用无显著影响。结论A3AR参与失血性休克血管低反应性的形成,其机制可能部分与BK通道有关。     

腺苷A2A受体：机体免疫调节的重要分子

腺苷A2A受体是目前已知的四种腺苷受体（A1、A2A、A2B和A3）之一,其在免疫细胞上呈高水平表达,活化后可通过对免疫细胞功能的调控而密切参与炎性反应、免疫耐受等免疫调节。但在不同的病理条件下,A2A受体活化的免疫调节作用方向不同、产生的效应不同。因此,对该受体产生不同免疫调节作用原因及机制进行深入的研究,以有效发挥其保护作用,而避免损伤效应,将为在临床疾病的免疫治疗中合理利用A2A受体调节剂奠定基础。     

The RegEx trial: a randomized, double-blind, placebo- and active-controlled pilot study combining regadenoson, a selective A2A adenosine agonist, with low-level exercise, in patients undergoing myocardial perfusion imaging

Background  Although vasodilator stress myocardial perfusion imaging (MPI) is increasingly performed with exercise, adenosine A_2A receptor agonists have not been studied with exercise. Objectives  To determine the safety of administering regadenoson during exercise and, secondarily, to evaluate image quality, patient acceptance, and detection of perfusion defects. Methods  Patients requiring pharmacologic MPI received a standard adenosine-supine protocol (AdenoSup, n = 60) and were then randomized (2:1) in a double-blind manner to low-level exercise with bolus intravenous injection of regadenoson (RegEx, n = 39) or placebo (PlcEx, n = 21). Results  Adverse events occurred in 95%, 77%, and 33% of patients receiving AdenoSup, RegEx, and PlcEx, respectively. Peak heart rate was 13 beats per minute (bpm) and 21 bpm greater following RegEx compared to that following PlcEx and AdenoSup, respectively (P = .006 and <.001). Change from baseline in mean systolic blood pressure (SBP), change from baseline to nadir SBP, and percentage of patients with a decline in SBP by ≥20 mm Hg showed no important differences between RegEx and PlcEx. No occurrences of 2nd degree or higher AV block were observed following RegEx or PlcEx; one patient developed 2nd degree AV block following AdenoSup. The mean heart-to-liver and heart-to-gut ratios were improved on RegEx vs AdenoSup: 0.85 (0.34) vs 0.65 (0.26), P < .001 and 1.1 (0.36) vs 0.97 (0.34), P < .001, respectively. Compared to AdenoSup, 70% of patients felt RegEx was much or somewhat better. Conclusions  Combining regadenoson with low-level exercise is feasible, well tolerated, and associated with fewer side effects compared to AdenoSup. Presented, in part, at American College of Cardiology 56th Annual Scientific Session, New Orleans LA, March 25, 2007.     

电针结合重复经颅磁刺激对局灶性脑缺血大鼠蛋白激酶A-环磷腺苷反应元件结合蛋白信号转导通路的影响

Objective To investigate the effects of electro-acupuncture (EA) combined with repetitive transcranial magnetic stimulation (rTMS) on protein kinase A-cyclic adenosine monophosphate response element binding protein (PKA-CREB) signal transduction system after focal cerebral ischemia in adult rats and to explore the mechanism of EA combined with rTMS in treating ischemic brain injury.Methods The animal model of transient focal ischemia was made by artificial middle cerebral artery occlusion. Seventy-five Wistar rats were randomly divided into normal group, model group, EA group, rTMS group and EA+rTMS group. The expressions of PKA and pCREB in hippocampus were detected and the neurologic impairment rating was observed at the 7th, 14th and 28th days, respectively, after infarction.Results The average gray densities of PKA and pCREB expressions in hippocampus after focal cerebral ischemia in model group were higher at the 7th d, lower at the 28th d than that in normal group (P＜0.05);higher in EA group, rTMS group, EA+rTMS group than that in model group at all time points (P＜0.05), higher in EA+rTMS group than that in EA group and rTMS group at 7th and 14th d(P＜0.05), and there was no difference between EA group and rTMS group(P＞0.05).The improvement of neural motor function was obvious in EA group, rTMS group and EA+rTMS group compared with model group (P＜0.01), especially in EA+rTMS group.Conclusions EA combined with rTMS can promote the functional recovery after cerebral ischemia,enhance the expression of PKA-CREB signal transduction system in hippocampus after focal cerebral ischemia, which might be one of the important mechanisms of EA combined with rTMS in treating ischemia brain injury.