力竭运动过程中大鼠纹状体葡萄糖/乳酸代谢的实时观察

目的:通过实时观察一次性力竭运动过程中大鼠纹状体葡萄糖和乳酸浓度的动态变化规律,揭示运动性中枢疲劳形成过程中脑能量代谢的特征。方法:8周龄雄性Wistar大鼠20只分为两组,纹状体葡萄糖、乳酸测定组(第1组)和外周血葡萄糖、乳酸测定组(第2组),每组10只。采用微透析-电化学联用的活体检测技术,实时监测大鼠(第1组)在一次性力竭运动过程中纹状体细胞外液中葡萄糖和乳酸的代谢变化,并从尾静脉采血动态监测大鼠(第2组)外周血液中葡萄糖和乳酸浓度的变化。结果:(1)与安静状态相比,运动初期大鼠纹状体胞外乳酸浓度显著升高(P<0.05),运动后期直至恢复期均显著降低(P<0.05,P<0.01);而胞外葡萄糖浓度在运动初期无明显变化,在运动后期开始下降,甚至在恢复期的90分钟内仍显著低于安静水平(P<0.05,P<0.01)。(2)大鼠外周血糖浓度随着运动时间的延长而显著降低,在运动力竭以及恢复期血糖水平均显著低于安静水平(P<0.05,P<0.01);大鼠血乳酸浓度在力竭运动过程中显著高于安静时水平(P<0.05),而在运动结束后即迅速恢复至安静时水平。结论:力竭运动过程中,持续的外周低血糖导致脑对于葡萄糖摄取不足,出现脑葡萄糖和乳酸浓度降低,中枢能量物质葡萄糖和乳酸代谢的显著降低可能是产生运动性中枢疲劳的一个重要的神经生物学机制。     

力竭运动对大鼠纹状体、中脑及下丘脑单胺类神经递质含量的影响

为观察力竭性跑台运动对大鼠纹状体、中脑及下丘脑单胺类神经递质含量的影响 ,本研究采用高效液相色谱 -电化学检测法测定了安静时、运动后即刻和运动后 2 4小时大鼠纹状体、中脑及下丘脑多巴胺 (DA)、去甲肾上腺素 (NE)和 5 -羟色胺 (5 -HT)水平。结果显示 ,力竭运动后即刻下丘脑DA水平显著降低 ,运动后中脑NE水平和运动后 2 4小时纹状体的NE水平升高 ;运动后纹状体和下丘脑内 5 -HT有升高的趋势 ;中脑的DA/ 5 -HT比值在运动后显著性升高 ,而在下丘脑中则显著性下降。提示 ,大鼠运动至力竭时 ,中枢神经系统的抑制是多种递质共同作用的结果 ;运动导致的中枢神经系统的抑制过程并不是在全脑均衡发生的 ,中脑表现一定的兴奋性作用 ,而在下丘脑则表现为抑制 ;DA/ 5 -HT的比值是评定中枢神经系统疲劳的敏感性指标 ,其比值下降可能伴有中枢疲劳的发生     

力竭运动过程中大鼠纹状体神经元局部场电活动的动态研究

目的:探讨大鼠在安静、运动、疲劳、恢复等不同状态下纹状体神经元电活动变化特征与运动能力的关系。方法:采用金属微电极植入和在体电生理记录技术,连续动态观察一次性力竭运动过程中大鼠纹状体神经元局部场电位(LFPs)活动,并对大鼠运动能力进行观察。结果:一次性力竭运动过程中大鼠纹状体神经元LFPs活动呈动态变化规律,主要表现为:与安静状态相比,运动过程中放电频率逐渐升高、幅度逐渐降低,力竭后逐渐降低至安静水平。结论:在力竭运动过程中,纹状体LFPs活动的动态变化具有明显的阶段性特征,该脑区LFPs电活动的改变与运动疲劳有关。在运动初期纹状体主要是通过直接通路参与皮层运动的调控,而在运动后期,则主要通过间接通路发挥作用。提示:两条通路的平衡失调是导致大鼠运动能力下降的重要原因之一。     

力竭运动前后活体大鼠纹状体谷氨酸和γ-氨基丁酸水平的动态变化

目的:观察一次性力竭运动过程中大鼠纹状体内神经递质谷氨酸(Glu)和γ-氨基丁酸(GABA)含量及其比值的动态变化,探讨运动疲劳后纹状体神经元电活动改变的可能机制.方法:8周龄雄性Wistar大鼠8只,通过手术预先将透析套管定植入左侧纹状体(P:0.2,L:3,H:3.2).采用活体微透析与高效液相色谱(HPLC)检测...     

力竭运动后大鼠海马脑区谷氨酸受体NR2A蛋白含量和基因表达的变化

目的:观察力竭运动前后大鼠脑中海马谷氨酸受体NR2A蛋白含量和基因表达的变化,探讨其与运动性疲劳的可能联系。方法:50只SD雄性大鼠,随机分为安静对照组(S,n=10),力竭运动后即刻组(AE1,n=10),力竭运动后恢复0.5小时组(AE2,n=10),力竭运动后恢复3小时组(AE3,n=10)和力竭运动后恢复24小时组(AE4,n=10)。分别采用免疫印迹法和RT-PCR法测定一次性力竭运动后大鼠脑中海马谷氨酸受体NR2A蛋白含量和基因表达。结果:与安静对照组相比,力竭运动后即刻,大鼠NR2A蛋白含量明显升高,而mRNA表达显著减少;恢复0.5小时后,蛋白含量略有下降,mRNA表达显著增加;恢复3小时后蛋白含量显著下降,mRNA表达继续增加;恢复24小时后蛋白含量恢复到安静时水平,mRNA表达则减少至恢复0.5小时后水平。结论:力竭运动后即刻及恢复过程中,大鼠脑中海马谷氨酸受体NR2A蛋白含量及mRNA表达变化趋势不同,提示基因表达对蛋白含量的调控可能具有延迟性。     

力竭运动后大鼠脑皮质运动区谷氨酸受体NR2A蛋白含量及酪氨酸磷酸化水平的变化

目的:观察力竭运动前后大鼠脑皮质运动区NR2A蛋白含量及其自身酪氨酸磷酸化水平变化,分析二者之间的相关关系,为探讨中枢兴奋信号在运动中的传递机理以及运动性疲劳的中枢机制提供实验依据。方法:SD大鼠进行一次性力竭跑台运动。采用抗NR2A抗体和抗磷酸酪氨酸单抗以免疫沉淀法和免疫印迹法检测皮质运动区NR2A蛋白含量及酪氨酸磷酸化水平。结果:力竭运动后即刻,大鼠脑皮质运动区NR2A蛋白含量与安静组相比无显著性变化,运动后1小时与安静组和运动后即刻比较显著升高(P<0.05,P<0.01),运动后3小时NR2A蛋白含量下降,运动后恢复24小时大鼠脑皮质中NR2A蛋白含量显著低于安静组和运动后即刻组(P<0.01,P<0.05)。NR2A酪氨酸磷酸化水平力竭运动后与对照组相比呈升高趋势但无显著性差异,NR2A酪氨酸磷酸化水平与NR2A蛋白含量变化无显著相关。结论:(1)大鼠在力竭运动后即刻及恢复期过程中,大脑皮质运动区NR2A蛋白含量变化表现为下降,上升,再下降,表明运动过程中NR2A蛋白含量变化具有较敏感的可调控性,力竭运动后即刻NR2A蛋白含量的下降可能是导致中枢抑制的一个因素。(2)NR2A酪氨酸磷酸化水平在力竭运动后呈升高趋势,可能有利于维持中枢的兴奋性,提示运动过程中NR蛋白含量的变化可能是多方面原因造成的,受体蛋白含量与受体活性之间可能存在较为复杂的关系。     

运动预处理对心肌SarcK_(ATP)通道亚基Kir6.2和SUR2A蛋白表达的影响

目的:探讨运动预处理对心肌肌膜ATP敏感钾(Sarc KATP)通道亚基内向整流钾通道6.2(Kir6.2)和磺酰脲受体(SUR2A)蛋白表达变化的影响。方法:48只SD大鼠分对照组(C组)、力竭运动组(EE组)、早期运动预处理组(EEP组)、早期运动预处理+力竭运动组(EEP+EE组)、晚期运动预处理组(LEP组)、晚期运动预处理+力竭运动组(LEP+EE组),每组8只。一次大强度间歇跑台运动建立运动预处理模型,大强度力竭跑台运动建立力竭运动模型。用免疫荧光组织化学方法观察Kir6.2和SUR2A蛋白表达分布变化,用免疫印迹方法检测Kir6.2和SUR2A蛋白表达。结果:与C组相比,EE组心肌Kir6.2和SUR2A蛋白表达水平显著上升,EEP组心肌Kir6.2蛋白表达水平显著降低,LEP组心肌SUR2A蛋白表达水平显著降低。与EE组相比较,EEP+EE和LEP+EE组心肌Kir6.2和SUR2A蛋白表达水平显著降低。结论:运动预处理对心肌Sarc KATP通道Kir6.2和SUR2A蛋白水平在早、晚期不同阶段的影响并不完全一致,而该通道Kir6.2和SUR2A蛋白水平在运动预处理诱导减轻力竭运动所致大鼠运动性心肌损伤保护效应中的变化趋势是一致的。心肌Sarc KATP通道通过Kir6.2和SUR2A蛋白水平变化参与了运动预处理诱导的减轻力竭运动所致大鼠运动性心肌损伤保护效应。     

力竭运动后大鼠海马CA1区自由基、下丘脑GABA及HPA轴的动态变化

目的:探讨运动性疲劳时神经内分泌系统的中枢调控机制。方法:50只SD大鼠随机分为安静对照组和力竭性游泳运动组,力竭组大鼠进行一次性力竭游泳运动,运动后即刻、1h、3h和24h断头取材。用放免法测定下丘脑促肾上腺激素释放激素(CRH)、血清肾上腺皮质激素(ACTH)和血清皮质酮(C);DNS-Cl荧光光度法测定下丘脑γ-氨基丁酸(GABA)含量;顺磁共振波谱法测定PBN自旋捕获剂捕获的海马CA1区自由基含量。结果:(1)力竭运动后即刻和恢复1小时组大鼠下丘脑CRH显著低于安静对照组;运动后即刻组血清ACTH浓度低于安静对照组,运动后1小时和3小时组高于安静对照组,但均无显著性差异;运动后即刻组血清C明显高于安静对照组。(2)与安静对照组相比,力竭运动后即刻、1小时和3小时组大鼠下丘脑GABA含量均显著升高。(3)与安静对照组相比,运动后即刻组大鼠海马CA1区自由基信号强度显著增强。(4)下丘脑GABA含量与下丘脑CRH呈显著负相关;海马CA1区自由基信号强度与下丘脑GABA含量呈显著正相关;海马CA1区自由基信号强度与下丘脑CRH呈显著负相关。结论:(1)下丘脑GABA可能通过直接作用于CRH神经元参与抑制运动应激时下丘脑-垂体-肾上腺皮质(HPA)轴的过度激活,并将运动疲劳时中枢的抑制状态传递到外周,使机体免受HPA轴过度激活带来的损伤。(2)力竭性运动时海马CA1区神经元自由基的增加使兴奋性增强,并可能通过Glu-GABA突触联系间接对HPA轴活性进行抑制。     

腺苷A2A受体对小鼠精神运动和情绪行为的调控作用

目的探讨腺苷A2A受体基因敲除、A2A受体激动剂干预或A2A受体抑制剂干预对小鼠运动活性、焦虑和抑郁样行为的影响。方法取腺苷A2A受体基因敲除(A2AKO)的雄性小鼠(A2AKO组)及同窝野生型(WT)C57BL/6小鼠(WT组)待用。另取雄性清洁级C57BL/6小鼠,随机分为SCH58261组、CGS21680组和对照组,分别给予腺苷A2A受体特异性拮抗剂SCH58261(2mg/kg)、腺苷A2A受体特异性激动剂CGS21680(0.5mg/kg)和同体积(0.25ml)载体溶液(二甲基亚砜+生理盐水)腹膜腔注射,10min后待用。前述各组别小鼠均进行旷场、高架十字迷宫和强迫游泳实验,测定各组小鼠的运动活性、焦虑和抑郁样行为。结果与WT组比较,A2AKO组旷场总运动路程缩短(P<0.001),周边区域的滞留时间延长(P<0.05),进入高架十字迷宫开臂的次数及在开臂滞留时间减少(P<0.05),强迫游泳的累计不动时间无显著差异(P>0.05),而CGS21680组旷场总运动路程缩短(P<0.01),周边区域滞留时间延长(P<0.01),进入高架十字迷宫开臂的次数及在开臂的滞留时间减少(P<0.01),强迫游泳的累计不动时间延长(P<0.001),而SCH58261组旷场总运动路程和中心区域活动路程延长(P<0.001),强迫游泳的累计不动时间缩短(P<0.01),高架十字迷宫试验各项指标无显著差异(P>0.05)。结论腺苷A2A受体激动剂可减少小鼠的自发和探索行为,加重焦虑和抑郁情绪,该效应与腺苷A2A受体基因敲除引发的效应相似,与腺苷A2A受体拮抗剂引发效应相反。     

力竭运动对大鼠大脑P2X_2、P2X_4和P2X_6受体表达的影响

目的:探讨一次和反复力竭游泳运动后大鼠大脑ATP受体P2X之三个亚型P2X2、P2X4和P2X6的时相性变化特点。方法:健康成年雄性SD大鼠68只,分为一次力竭游泳运动组和反复力竭游泳运动组及安静对照组,反复力竭组大鼠每日负重3%体重进行力竭游泳运动,共训练2周。运动组分别于力竭运动后即刻、4小时、12小时和24小时取材,采用实时荧光定量PCR方法测定力竭运动后大鼠P2X2、P2X4和P2X6受体亚型mRNA水平。结果:(1)反复力竭运动后12小时组P2X2相对表达率达到峰值,与反复力竭其它各组及安静对照组、一次力竭12小时组均有显著差异(P<0.01)。(2)一次力竭即刻组P2X4相对表达率与安静对照组、4小时组、12小时组比较有显著统计学差异(分别为P<0.01、P<0.05、P<0.01)。(3)反复力竭运动后12小时组P2X6相对表达率达到峰值。结论:3种受体亚型在一次力竭运动和反复力竭运动后12小时出现峰值或峰值趋势,提示在力竭运动后12小时,这3种P2X受体亚型所参与的中枢神经生理生化活动在此时可能会达到一个活跃期。     

pIRES2-EGFP-hBMP2载体在人骨髓基质细胞中的表达及意义

目的：研究人骨形成蛋白hBMP2真核表达载体pIRKS2-EGFP-hBMP2在人骨髓基质细胞系HFCL中的表达及意义。方法：利用DNA重组技术，将hBMP2片段克隆到真核表达载体pIRES2-EGFP中；EeoRI/BamHI双酶切鉴定；脂质体介导的方法转染HFCL．细胞；荧光显微镜下观察转染细胞；免疫组化染色检测hBMP2基因的表达。结果：经酶切鉴定显示，成功地构建了重组载体pIRES2-EGFP-hBMP2。转染HFCL 48h后在荧光显微镜下观察到转染的HFCL细胞发绿色荧光。免疫组化染色显示转染hBMP2基因的HFCL细胞浆内有细的棕色颗粒，而转染空载体的HFCL细胞免疫组化呈阴性。结论：所构建的pIRES2-EGFP-hBMP2真核表达载体在HFCL细胞中有良好的表达，为进一步研究转基因骨髓基质细胞对放射和化疗所致的造血和骨微环境破坏的改善奠定了基础。     

EphB-2受体及HER-2与EGFR在结直肠癌中的表达与意义

目的探讨EphB-2受体、HER-2、EGFR的表达与结直肠癌生物学行为的关系。方法采用免疫组化染色检测86例结直肠癌组织标本中EphB-2受体、HER-2、EGFR的表达水平,以结直肠腺瘤组织标本47例作为对照。结果在癌旁无瘤黏膜、结直肠腺瘤和结直肠癌3组中,EphB-2受体的表达阳性率分别为100%（86/86）、95.7%（45/47）和83.7%（72/86）;HER-2表达阳性率分别为34.9%（30/86）、42.6%%（20/47）和74.4%（64/86）;EGFR表达阳性率分别为39.5%（34/86）、46.8%（22/47）和65.1%（56/86）,癌旁无瘤黏膜、结直肠腺瘤与结直肠癌阳性率比较差异具有统计学意义（P〈0.05）。在结直肠癌中EphB-2受体的表达与结直肠癌的分化程度、浸润深度、淋巴结转移有关,而HER-2、EGFR的表达与结直肠癌的浸润深度、淋巴结转移有关。结论 EphB-2受体、HER-2、EGFR对结直肠癌生物学行为有明显影响,可作为临床判断结直肠癌的生物学行为及预后的重要参考指标。     

狼疮性肾炎患者血清中白介素2及可溶性白介素2受体水平的研究

 目的 探讨血清白介素2(IL-2)、可溶性白介素2受体(sIL-2R)与狼疮性肾炎(LN)的关系.方法 IL-2、sIL-2R检测采用酶联免疫吸附实验法(ELISA).结果 (1)LN患者血清IL-2水平显著低于正常对照组,经治疗后IL-2水平上升不明显,仍低于正常对照组,(2)LN患者血清sIL-2R水平显著高于正常对照组,经治疗后sIL-2R水平明显下降,但仍高于正常对照组.(3)LN患者血清IL-2水平与抗dsDNA抗体滴度及血清补体C3无显著相关;而sIL-2R水平与抗dsDNA抗体滴度呈正相关,与血清补体C3呈负相关.结论 IL-2、sIL-2R可能参与了LN的发病;sIL-2R水平与LN的活动性相关.     

vGRASE: separating phase and T(2) modulations in 2D.

A new fast imaging technique, vGRASE, was designed and implemented on a clinical imager. In the vGRASE scheme, the T(2) modulation ghost, which is the main problem of the GRASE sequence, can be reduced by separating the phase and T(2) modulations in two encoding directions. Although it is not much faster than the original GRASE, vGRASE has much improved image quality, with the same advantages over RARE and EPI as the original GRASE.     

Age-dependent normal values of T2* and T2' in brain parenchyma

BACKGROUND AND PURPOSE: Physiologic age-related T2* and T2′ values are required as reference for comparison with disease-related deviations. In our study, T2* and T2′ values (T2 values as control) were determined with MR imaging in healthy subjects to determine standard values and investigate age-related changes.MATERIALS AND METHODS: Data of 50 patients without intraparenchymal pathology and 10 acute stroke patients who underwent MR imaging including a T2 and T2* sequence with 3 echotimes were included. After calculation of T2*, T2′, and T2 maps, the values of gray matter (GM) and white matter (WM) for each hemisphere were measured in 6 distinct regions of interest (ROIs).RESULTS: There was a negative correlation between age and T2* values in the caudate nucleus (r = −0.34 Pearson correlation; P = .001) and lentiform nucleus (r = −0.67; P = .001) and a positive correlation in the occipital (r = 0.41; P = .001) and subcortical (r = 0.45; P = .001) WM. An age dependency for T2′ values was only found for the caudate (r = −0.35; P = .001) and lentiform nucleus (r = −0.69; P = .001). T2′ values in acute stroke were lower than normal in all patients with stroke.CONCLUSION: Decrease in T2′ and T2* values in GM and increase of T2* values in WM correlate with the progress of brain aging. Explanations for decreasing T2′ and T2* values include iron deposition in the caudate and lentiform nucleus. In contrast to T2* values, there is no association of T2′ values with the degree of leukoaraiosis. These age-dependent values can be used as a reference in neurovascular diseases and for the discussion of functional MR imaging data.

The possibility of measurements of T2* and T2′ values is of considerable interest for the application of MR imaging in the evaluation of cerebral disease. The use of quantitative techniques potentially increases the diagnostic sensitivity and specificity in the characterization of brain tissue pathologic processes. T2* and T2′ values represent intrinsic parameters of tissue that determine MR imaging signal intensity. These values are sensitive to changes in chemical composition and metabolic modifications that accompany cerebral pathologic processes. T2′ is equal to T2* corrected for spin-spin effects and therefore better isolates the influences of deoxyhemoglobin on T2* values according to the formula 1/T2′ = 1/T2*−1/T2.^1,2Quantitative MR values have been used in several studies for different conditions. Measurement of T2 values is used in the diagnosis of leukoencephalopathy or developmental anomalies of gray (GM) and white matter (WM) in children.³ It has been known for a long time that age-dependent changes in brain structure and metabolism are associated with changes of relaxation values.⁴ Measurement of T2* and T2′ values has been used for determination of iron tissue concentration,⁵ and calculation of T2′ values has already been used in MR imaging in acute stroke to investigate the oxygen extraction fraction (OEF) in acute ischemic stroke^2,6 and chronic misery perfusion.^7,8 However, normal reference T2′ values have not been reported so far, and the determination of T2′ reference values is mandatory for future applications in ischemic disease. In our study, T2* and T2′ values (and T2 values as control) were determined with MR imaging in distinct regions of interest (ROIs) in the WM and in the basal ganglia in subjects without intraparenchymal pathologic processes to determine age-related normal values. To prove applicability of the obtained T2′ normal values, in addition, T2′ values were measured in 10 patients with acute stroke.     

HER2放射性配体99Tcm-ABH2的制备及荷乳腺癌裸鼠显像

目的 制备99 Tcm-人表皮生长因子受体2(HER2)亲和体(ABH2),探讨其作为HER2阳性乳腺癌分子显像剂的可行性.方法 以葡庚糖酸钠和SnC12·2H2O为标记体系在ABH2上标记99Tcm,测定标记产物的标记率和放化纯,再用PBS和血清测定标记后6.0h内的稳定性.用表达HER2的MBA-MD-361乳腺癌细胞测定99Tcm-ABH2的平衡解离常数(Kd).于4只荷MBA-MD-361乳腺癌小鼠尾静脉注射37 MBq 99Tcm-ABH2,注射后1.0、4.5 h进行SPECT/CT显像,计算肿瘤对肝脏、大脑、肺、心脏、骨骼、肌肉的T/NT,2d后预先注射200 μg未标记的ABH2,再注射37 MBq 99Tcm-ABH2,以相同方法显像,应用单因素方差分析对比不同显像的T/NT.结果 99 Tcm-ABN2标记率在99％以上,其在PBS和血清中都稳定,在血清中37 ℃保温6.0 h放化纯达(95.0±1.0)％.99Tcm-ABH2的Kd为1.7 nmol/L.荷瘤鼠注射99Tcm-ABH2后1.0和4.5h显像见乳腺癌的放射性摄取,99 Tcm-ABH2主要从泌尿系统清除;4.5 h肿瘤对肝脏、肺、大脑、心脏、肌肉、骨骼的T/NT分别为1.81±0.60、8.95±1.13、20.08±6.12、7.61±0.56、10.62± 1.78、11.422.07;阻断后注射99Tcm-ABH2,4.5 h相应T/NT分别为0.60±0.23、3.05± 1.38、5.24±2.17、2.42± 1.02、8.16±2.66、2.76±0.48(F=29.38,P＜0.05).结论 成功制备了高纯度的99Tcm-ABH2,荷瘤鼠实验表明99Tcm-ABH2能够特异地对HER2阳性乳腺癌进行显像.     

123/125I-labelled 2-iodo-L-phenylalanine and 2-iodo-D-phenylalanine: comparative uptake in various tumour types and biodistribution in mice

Purpose In vitro in the R1M cell model and in vivo in the R1M tumour-bearing athymic model, both [¹²³I]-2-iodo-L-phenylalanine and [¹²³I]-2-iodo-D-phenylalanine have shown promising results as tumour diagnostic agents for SPECT. In order to compare these two amino acid analogues and to examine whether the observed characteristics could be generalised, both isomers were evaluated in various tumour models.Methods Transport type characterisation in vitro in A549, A2058, C6, C32, Capan2, EF43fgf4, HT29 and R1M cells with [¹²³I]-2-iodo-L-phenylalanine was performed using the method described by Shotwell et al. Subsequently, [¹²³I]-2-iodo-L-phenylalanine and [¹²³I]-2-iodo-D-phenylalanine tumour uptake and biodistribution were evaluated using dynamic planar imaging and/or dissection in A549, A2058, C6, C32, Capan2, EF43fgf4, HT29 and R1M inoculated athymic mice. Two-compartment blood modelling of the imaging results was performed.Results In vitro testing demonstrated that [¹²³I]-2-iodo-L-phenylalanine was transported in all tumour cell lines by LAT1. In all tumour models, the two amino acid analogues showed the same general biodistribution characteristics: high and specific tumour uptake and renal tracer clearance. Two-compartment modelling revealed that the D-isomer showed a faster blood clearance together with a faster distribution to the peripheral compartment in comparison with [¹²³I]-2-iodo-L-phenylalanine.Conclusion [¹²³I]-2-iodo-L-phenylalanine and its D-isomer are promising tumour diagnostic agents for dynamic planar imaging. They showed a high and similar uptake in all tested tumours. [¹²³I]-2-iodo-D-phenylalanine showed better tracer characteristics concerning radiation dose to other organs.     

R2 and R2* mapping for sensing cell-bound superparamagnetic nanoparticles: in vitro and murine in vivo testing

PURPOSE: To prospectively determine the cellular iron uptake by using R2 and R2* mapping with multiecho readout gradient-echo and spin-echo sequences. MATERIALS AND METHODS: All experiments were approved by the institutional animal care committee. Lung carcinoma cells were lipofected with superparamagnetic iron oxides (SPIOs). Agarose gel phantoms containing (a) 1 x 10(5) CCL-185 cells per milliliter of agarose gel with increasing SPIO load (0.01-5.00 mg of iron per milliliter in the medium), (b) different amounts (5.0 x 10(3) to 2.5 x 10(5) cells per milliliter of agarose gel) of identically loaded cells, and (c) free (non-cell-bound) SPIOs at the iron concentrations described for (b) were analyzed with 3.0-T R2 and R2* relaxometry. Iron uptake was analyzed with light microscopy, quantified with atomic emission spectroscopy (AES), and compared with MR data. For in vivo relaxometry, agarose gel pellets containing SPIO-labeled cells, free SPIO, unlabeled control cells, and pure agarose gel were injected into three nude mice each. Linear and nonlinear regression analyses were performed. RESULTS: Light microscopy and AES revealed efficient SPIO particle uptake (mean uptake: 0.22 pg of iron per cell +/- 0.1 [standard deviation] for unlabeled cells, 31.17 pg of iron per cell +/- 4.63 for cells incubated with 0.5 mg/mL iron). R2 and R2* values were linearly correlated with cellular iron load, number of iron-loaded cells, and content of freely dissolved iron (r(2) range, 0.92-0.99; P < .001). For cell-bound SPIO, R2* effects were significantly greater than R2 effects (P < .01); for free SPIO, R2 and R2* effects were similar. In vivo relaxometry enabled accurate prediction of the number of labeled cells. R2' (R2* - R2) mapping enabled differentiation between cell-bound and free iron in vitro and in vivo. CONCLUSION: Quantitative R2 and R2* mapping enables noninvasive estimations of cellular iron load and number of iron-labeled cells. Cell-bound SPIOs can be differentiated from free SPIOs with R2' imaging.     

MDM2基因与肿瘤放射生物效应

鼠双微体2(MDM2)基因是电离和紫外线辐射反应中的关键组分,MDM2表达水平决定辐射诱导的抑癌基因p53活性增加程度。MDM2可以限制p53的凋亡功能,是许多类型细胞的存活因子。另外,DNA损伤诱导MDM2的表达,一般认为高水平的MDM2蛋白可以缩短辐射后p53建立的细胞周期阻滞。MDM2表达的增加似乎可以保证存活细胞中p53的活性回复到较低的基础水平。MDM2水平的降低增加了细胞对电离辐射的敏感性。因此,MDM2是介入治疗的潜在靶点。