In vivo detection of single cells by MRI.

The use of high-relaxivity, intracellular contrast agents has enabled MRI monitoring of cell migration through and homing to various tissues, such as brain, spinal cord, heart, and muscle. Here it is shown that MRI can detect single cells in vivo, homing to tissue, following cell labeling and transplantation. Primary mouse hepatocytes were double-labeled with green fluorescent 1.63-microm iron oxide particles and red fluorescent endosomal labeling dye, and injected into the spleens of recipient mice. This is a common hepatocyte transplantation paradigm in rodents whereby hepatocytes migrate from the spleen to the liver as single cells. One month later the animals underwent in vivo MRI and punctuated, dark contrast regions were detected scattered through the livers. MRI of perfused, fixed samples and labeled hepatocyte phantoms in combination with histological evaluation confirmed the presence of dispersed single hepatocytes grafted into the livers. Appropriate controls were used to determine whether the observed contrast could have been due to dead cells or free particles, and the results confirmed that the contrast was due to disperse, single cells. Detecting single cells in vivo opens the door to a number of experiments, such as monitoring rare cellular events, assessing the kinetics of stem cell homing, and achieving early detection of metastases.     

消化性溃疡病因分析

[目的]探讨幽门螺旋杆菌感染和非甾体类消炎药应用与消化性溃疡的关系．[方法]对1062例消化不良患者进行内窥镜检壹、快速尿素酶实验和血清抗幽门螺旋杆菌免疫球蛋白检验，同时记录非甾体类消炎药的应用情况，计算消化不良患者消化性溃疡发病事、幽门螺旋杆菌感染率及非甾体类消炎药应用率．[结果]溃疡发病率为29．3％，幽门螺旋杆菌感染串为37．2％，非甾体类消炎药使用率为10．0％．[结论]幽门螺旋杆菌及非甾体类消炎药相互作用干上消化道黏膜．是引发消化性溃疡的重要病因．     

不同微生物诱导家蝇幼虫表达抗菌肽的特性

研究不同微生物诱导家蝇幼虫表达的抗菌肽特性.用3种不同的病源菌通过针刺感染的方法诱导家蝇幼虫表达抗菌肽,通过Sephadex G25分离,用Hult mark改进法和抑菌圈测定法作抑菌试验,用毛细管电泳（CE）分析不同微生物诱导得到的抗菌肽样品差异,检测抗菌肽的热稳定性和酸碱耐受性.发现不同微生物诱导产生的家蝇抗菌肽具有广谱抑菌性,但不同样品对不同病源菌抑菌活性有差异,不同测定抑菌效果的方法对抑菌结果有影响,各种抗菌肽样品CE蛋白谱具有明显不同.抗菌肽样品都具有热稳定性和酸碱耐受性.说明不同微生物诱导产生的家蝇抗菌肽类型以及抗菌肽含量与诱导源有关,抗菌肽为家蝇幼虫体内固有成分,诱导增加了抗菌肽的表达量同时刺激新抗菌肽的产生.用志贺氏菌、金黄色葡萄球菌、鼠伤寒沙门氏菌诱导家蝇幼虫可产生较多含量高活性好的抗菌肽.     

低剂量他克莫司治疗大鼠急性脊髓损伤的实验研究

目的：探讨低剂量他克莫司（tacrolimus，又名FK506）对大鼠急性脊髓损伤是否具有神经保护作用。方法：雄性Wistar大鼠72只，随机分为假手术组（12只）、损伤组（30只）和FK506治疗组（30只）。采用Allen’s打击法致伤大鼠T10脊髓，假手术组仅做椎板切除术。FK506治疗组在脊髓损伤后5min一次性经尾静脉注射FK5060．3mg／kg，其余两组以相同方法给予等量生理盐水。致伤后30min、6h、24h、48h、72h取伤段脊髓组织行病理观察及原位末端标记法（TUNEL）检测神经细胞凋亡，伤后1、3、7、14、21d行脊髓功能BBB评分和斜板实验。结果：伤后3、7、14、21d，FK506治疗组斜板实验和BBB评分明显优于损伤组，两组间比较差异有显著性（P〈0．05）；伤后各时间点FK506治疗组脊髓损伤区出血坏死较损伤组轻；伤后6、24、48、72h神经细胞凋亡FK506治疗组较损伤组明显减少，两组间比较差异有显著性（P〈0．05）。结论：在大鼠急性脊髓损伤后早期应用低剂量他克莫司（0．3mg/kg）治疗对神经具有保护作用，可减少神经细胞凋亡，减轻脊髓继发性损伤，促进脊髓功能恢复。     

中药安迪注射剂对人食管癌细胞的放射增敏作用

目的 :观察安迪注射剂 (Andi)对电离辐射生物学效应的影响。方法 :人食管癌细胞株 (ECA 10 9)在富氧 (空气 )和缺氧 (通 99 99%的高纯氮气 5 0min)条件下分别观察对照组、Andi组、60 Co γ线辐射和Andi +60 Co γ线辐射 4组细胞形态 (光镜 )、细胞倍增时间 (TD)、存活率 (SR)及集落存活分数 (SF)。结果 :光镜下可见Andi组、辐射组、Andi+辐射组癌细胞变性、坏死、凋亡 ,以Andi +辐射组为最显著。MTT法测定对照组、Andi组、60 Co γ线辐射和Andi+60 Co γ线辐射四组缺氧细胞的TD(% )分别为 4 6 12 ,118 72 ,6 2 81,171 0 2h ,SR分别为 10 0 % ,4 2 % ,86 % ,30 % ;各治疗组与对照组比较TD 和SR均相差显著 (P <0 0 5 )。方差分析显示 ,辐射在富氧 (F =90 19,P =0 0 0 0 1)和缺氧 (F =37 0 9,P =0 0 0 0 3)时均为SF的影响因素 ;Andi仅在缺氧时对SF是有意义的影响因素 (F =2 9 0 4 ,P =0 0 0 0 7) ,与60 Co γ线辐射合用对缺氧细胞SF的影响具有协同作用 (F =11 37,P =0 0 0 98)。用单靶多击模型拟合数据分析 ,Andi的放射增敏比 (SER)为 1 5 ,相对敏化效应 (RSE)为 5 5 %。结论 :Andi对缺氧ECA 10 9细胞具有明显的细胞毒和放射增敏作用。     

Intubating conditions and onset of neuromuscular block of rocuronium (Org 9426); a comparison with suxamethonium

The intubating conditions and neuromuscular blocking profile following 600 micrograms.kg-1 rocuronium (Org 9426) have been investigated in patients under various experimental conditions. They were compared with conditions following 1.5 mg.kg-1 suxamethonium, preceded by a precurarising dose (10 mg) of gallamine, and with those in a control group in the absence of a muscle relaxant. Rocuronium produced good to excellent intubating conditions at 60 as well as at 90 s after administration, even though there was only a partial blockade of the adductor pollicis muscle. Intubating conditions following suxamethonium were comparable with those after rocuronium. Half of the control patients could be intubated. The clinical duration and the recovery time of 600 micrograms.kg-1 of rocuronium were 24(4) and 9(3) min (mean(s.d.)), respectively. Rocuronium may have a major advantage over existing non-depolarising muscle relaxants due to the early presence of excellent intubating conditions. The results indicate that rocuronium may replace suxamethonium in procedures in which rapid sequence induction is required.     

Antagonism of novel inotropic agents at A1 adenosine receptors and m-cholinoceptors in human myocardium

Summary The effects of the new inotropic agents saterinone, sulmazole, UD-CG 212.C1 and milrinone at A₁ adenosine receptors and m-cholinoceptors were evaluated in human myocardium from patients with heart failure. At A₁ adenosine receptors, all compounds inhibited ³H-DPCPX-binding to ventricular membrane preparations at micromolar concentrations. As judged from the K_i-values, the rank order of potency was saterinone > sulmazole > UD-CG 212.C1 > milrinone. The new inotropic agents also displaced the binding of ³H-QNB at m-cholinoceptors. Except for saterinone, the concentration ranges of mean K_i-values were considerably higher at m-cholinoceptors than at A₁ adenosine receptors. The rank order of potency was saterinone > sulmazole > UD-CG 212.Cl > milrinone. Competition of the A₁ adenosine receptor agonist R-PIA to ³H-DPCPX-binding showed a biphasic curve with a shallow slope (Hill coefficient n_H = 0.63) and revealed two affinity states of the A₁ adenosine receptor. In the presence of guanine nucleotides [Gpp(NH)p], the competition curve showed one low affinity class of binding sites and was shifted to the right. In contrast, the competition curves of the new inotropic agents were characterized by a monophasic, steeper slope (mean Hill coefficient n_H = 0.98). Guanine nucleotides had no effect. Similar results were obtained with saterinone and carbachol at m-cholinoceptors. Competition with carbachol revealed three affinity states of the m-cholinoceptor, the superhigh affinity binding was reversed by Gpp(NH)p. Competition with saterinone revealed one class of binding sites which was not influenced by Gpp(NH)p. Accordingly, in isolated, electrically driven human atrial trabeculae, the negative inotropic effect of adenosine was antagonized concentration-dependently by saterinone, sulmazole and UD-CG 212.Cl. Similarly the negative inotropic effect of carbachol was antagonized concentration-dependently by saterinone. It is concluded that the new inotropic agents bind to A₁ adenosine receptors and that their interaction is of antagonist nature. This mechanism might contribute to their capacity to enhance force of contraction by stimulation of cAMP-formation in addition to phosphodiesterase inhibition. The effects of saterinone may be partially due to antagonism at m-cholinoceptors. This is presumably not the case with the other inotropic agents studied given their low affinity for this receptor.Send offprint requests to M. Böhm at the above addressSupported by the Deutsche Forschungsgemeinschaft     

药物浓度和病因对三磷酸腺苷治疗阵发性室上性心动过速的影响

本文报告23例次ATP治疗PSVT的效果,总有效率56.5％,9例次高浓度快速注射者8例转复。器质性心脏病者副作用较多,1例冠心速注高浓度ATP后,发生心室颤动和阿-斯氏综合征。这一结果提示:药物浓度和注射速度是影响疗效的主要因素,PSVT伴AVB者疗效也很低;病因和药物浓度是决定副作用的因素。因此,对于器质性心脏病者,尤其冠心病人,应避免高浓度快速静脉注射ATP。     

肟类药物对塔崩等神经性毒剂抑制的大鼠脑AChE的体外重活化作用

系统地研究了肟类药物对塔崩抑制的大鼠脑AChE的体外重活化作用,并与梭曼、沙林和VX进行了比较。结果表明,沙林和VX抑制的AChE较易被药物重活化,而塔崩和梭曼抑制的AChE则较难。37℃、pH7.2条件下,塔崩抑制的大鼠脑AChE可浓度依赖性地被TMB_r和LuH_6重活化,2-PAM在高浓度下也有一定作用,但HI-6在所用3个浓度下均无重活化。通过降低抑制温度成功地建立了未老化的梭曼膦酰化AChE模型。药物试验表明,未老化的梭曼膦酰化大鼠脑AChE可被高浓度(1mmol/L)HI-6重活化,而不被2-PAM、TMB_4及LuH_6重活化。提示药物自身内在活性在重活化作用中的重要性。TMB_4和LuH_6对塔崩磷酸化AChE有较强重活化,而对未老化梭曼膦酸化AChE无重活化,HI-6则相反,对未老化梭曼膦酰化AChE重活化效果好,而对塔崩磷酰化AChE无重活化作用。塔崩和梭曼膦酰化AChE在未老化以前对药物的响应就有所不同,毒剂残基的空间效应可能起重要作用。