Axonal transport of dopamine D1 receptors in the rat brain

Binding of a specific dopamine D₁ receptor antagonist,¹²⁵I-SCH 23982, was measured in rat brain sections by quantitative autoradiography at various time intervals, following a knife cut through the striatonigral pathway. Twenty-four hours after lesioning, accumulations of D₁ receptor binding sites were found in sagittal sections both rostral and caudal to the lesion site. No other regions studied (caudate-putamen, nucleus accumbens, olfactory tubercle, and substantia nigra pars reticulata) showed any change in D₁ receptor binding 24h after the lesion. In brain sections obtained 10 days after lesioning, only the substantia nigra pars reticulata had a significant decrease in D₁ receptors ipsilateral to the lesion. These findings suggest the possibility of a presence of bidirectional axonal transport of D₁ receptors in rat striatonigral pathway.     

The effects of anesthesia on otoacoustic emissions

We have measured transient-evoked and distortion-product otoacoustic emissions (OAEs) in the chinchilla and compared them in the awake and anesthetized animal (using either ketamine or barbiturate agents). We report a significant increase in OAE amplitudes during anesthesia, particularly using ketamine. These effects are most evident for transient-evoked otoacoustic emissions (TEOAEs) as measured in the non-linear mode. Our data support the hypothesis that tonic activity levels in cochlear efferents may be reduced by anesthetic effects, either directly or indirectly (e.g., by general reductions in descending pathway activity), and that reduced cochlear efferent activity will result in the observed increase of OAE amplitudes.     

肝素对患感染性疾病的新生儿组织因子途径抑制物影响的观察

目的:观察肝素对患感染性疾病的新生儿组织因子途径抑制物(TFPI)的影响。方法:采用酶联免疫吸附试验(ELISA)法检测了32例患感染性疾病的新生儿在使用肝素前和使用肝素后30～45分钟、6小时血浆TFPI的变化,并与患儿对照组、正常对照组及文献进行比较。结果:患儿治疗组使用肝素后30～45分钟血浆TFPI水平明显增高(t=3.953,P<0.001),6小时血浆TFPI又几乎降至用药前水平(t=0.141,P<0.05)。结论:新生儿对肝素的反应与成人不同。     

Preselection Thymocytes Are More Sensitive to T Cell Receptor Stimulation Than Mature T Cells

During T cell development, thymocytes which are tolerant to self-peptides but reactive to foreign peptides are selected. The current model for thymocyte selection proposes that self-peptide–major histocompatibility complex (MHC) complexes that bind the T cell receptor with low affinity will promote positive selection while those with high affinity will result in negative selection. Upon thymocyte maturation, such low affinity self-peptide–MHC ligands no longer provoke a response, but foreign peptides can incidentally be high affinity ligands and can therefore stimulate T cells. For this model to work, thymocytes must be more sensitive to ligand than mature T cells. Contrary to this expectation, several groups have shown that thymocytes are less responsive than mature T cells to anti-T cell receptor for antigen (TCR)/CD3 mAb stimulation. Additionally, the lower TCR levels on thymocytes, compared with T cells, would potentially correlate with decreased thymocyte sensitivity. Here we compared preselection thymocytes and mature T cells for early activation events in response to peptide–MHC ligands. Remarkably, the preselection thymocytes were more responsive than mature T cells when stimulated with low affinity peptide variants, while both populations responded equally well to the antigenic peptide. This directly demonstrates the increased sensitivity of thymocytes compared with T cells for TCR engagement by peptide–MHC complexes.     

Radiofrequency Ablation of Concealed Left Free-Wall Accessory Pathways Without Coronary Sinus Catheterization:

Ablation of Concealed Accessory Pathways. Introduction: Feasibility of radiofrequency (RF) ablation using a two-catheter technique without coronary sinus catheterization was studied in 100 consecutive patients with a single concealed left free-wall accessory path-way.
Methods and Results: Tachycardia was induced by electrical stimulation in the right atrium/right ventricle, and the presence of a concealed left free-wall accessory pathway was suggested electrocardiographically (negative P wave in leads I and/or a VL during orthodromic tachycardia) or by earlier atrial activation in the pulmonary artery compared to the high right atrium. Mapping of the mitral annulus was performed during right ventricular pacing or orthodromic tachycardia, and RF energy was applied at the site with the earliest retrograde atrial activation. Ablation was considered effective if tachycardia could not be induced, and if VA dissociation or exclusive retrograde nodal conduction was observed. Ablation was initially successful in 98 of 100 patients. Mean number of radiofrequency pulses were 3.2 ± 2. Mean fluoroscopy time and total procedure time was 14 ± 9 and 107 ± 32 minutes, respectively. There were no complications related to the procedure. At a mean follow-up of 22 ± 13 months, two patients experienced tachycardia recurrence and required a second procedure, which was successful.
Conclusions: Our results suggest that RF catheter ablation of concealed left free-wall accessory pathways can be safely, effectively, and rapidly performed using a simplified two-catheter technique with no need for coronary sinus catheterization.     

Orthograde transport and release of insulin-like growth factor I from the inferior olive to the cerebellum

Insulin-like growth factor I (IGF-I) and its receptor are expressed in functionally related areas of the rat brain such as the inferior olive and the cerebellar cortex. A marked decrease of IGF-I levels in cerebellum is found when inferior olive neurons are lesioned. In addition, Purkinje cells in the cerebellar cortex depend on this growth factor to survive and differentiate in vitro. Thus, we consider it possible that IGF-I forms part of a putative trophic circuitry encompassing the inferior olive and the cerebellar cortex and possibly other functionally connected areas. To test this hypothesis we have studied whether IGF-I may be taken up, transported, and released from the inferior olive to the cerebellum. We have found that ¹²⁵I-IGF-I is taken up by inferior olive neurons in a receptor-mediated process and orthogradely transported to the cerebellum. Thus, radioactivity found in the cerebellar lobe contralateral to the injection site in the inferior olive was immunoprecipitated by an anti-IGF-I antibody, co-eluted with ¹²⁵I-IGF-I in an HPLC column, and co-migrated with ¹²⁵I-IGF-I in an SDS-urea polyacrylamide gel electrophoresis. Time-course studies indicated that orthograde axonal transport is relatively rapid since 30 min after the injection, radiolabeled IGF-I was already detected in the contralateral cerebellum. Furthermore, transport of IGF-i from the inferior olive is specific since when ¹²⁵I-neurotensin was injected in the inferior olive or when ¹²⁵I-IGF-I was injected in the pontine nucleus, no radiactivity was found in the contralateral cerebellum. In addition, no specific transport of ¹²⁵I-IGF-I was found in climbing fiber-deafferented rats or when excess unlabeled IGF-I was co-injected with ¹²⁵I-IGF-I. We next studied whether IGF-I is released by inferior olive neurons. We found that the release of IGF-I from cerebellar slices of normal rats was significantly greater in response to depolarizing stimuli than that from slices obtained of climbing fiber-deafferented animals. Indeed, in vitro release of IGF-I in response to KCI or veratridine was almost completely abolished in the latter. These data suggest that IGF-I is taken up by inferior olive neurons through IGF-I receptors and transported to the cerebellum through their axons without any major modification. Moreover, the release of IGF-I from the cerebellum after depolarization depends on the presence of climbing fiber afferents. Altogether these results indicate that the olivo-cerebellar pathway is able to take up, orthogradely transport, and release IGF-I. Since a similar process has been described in the visual system for basic fibroblast growth factor (bFGF), we propose that IGF-I, bFGF, and possibly other growth factors may constitute afferent trophic signals involved in plastic mechanisms within specific neural circuitries. © 1993 Wiley-Liss, Inc.     

导管射频消融术治疗持续性交界区反复性心动过速2例报告

本文报告两例持续性交界区反复性心动过速(PJRT)患者,应用导管射频消融术治疗,成功地阻断了位于后间隔具有递减传导特性的稳若旁路.随访7～10个月.病人无心动过速发作,提示导管射频消融术是治疗PJRT的有效方法.     

急性冠脉综合征患者强化抗栓治疗研究进展

急性冠脉综合征（ACS）是冠心病的严重类型,ACS患者不仅病死率较高,还存在缺血事件（如缺血性卒中、心肌梗死）复发风险。血小板聚集及血栓形成是导致ACS的重要原因。为降低缺血事件的发生风险,临床推荐ACS患者接受阿司匹林联合强效P2Y12抑制剂的双联抗血小板治疗12个月。然而在标准双联抗血小板治疗下,ACS患者残余缺血风险（经抗栓治疗后仍残留的缺血事件发生风险）仍旧较高。因此为进一步降低缺血事件发生风险,临床对强化抗栓方案的研究也逐渐增多。本文通过总结强化抗栓治疗方案的作用机制及其最新研究进展,发现延长双联抗血小板治疗时间、三联抗血小板治疗、双通道抑制（抗血小板联合抗凝治疗）等强化抗栓治疗方案可降低缺血事件发生风险,为进一步指导临床个体化抗栓治疗及明确最佳抗栓策略提供了参考。     

ACE2基因通过调控Nrf2/HO-1通路改善肾缺血再灌注损伤

目的 探讨血管紧张素转化酶2(ACE2)对缺氧复氧诱导的肾小管上皮细胞HK-2氧化应激、炎症、凋亡及核因子E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)信号通路的影响。 方法 将ACE2慢病毒转染HK-2细胞,按照实验需要分为常氧组(Control组)、缺氧复氧模型组(H/R组)、缺氧复氧转染阴性对照慢病毒组(H/R-NC组)和缺氧复氧转染ACE2慢病毒组(H/R-ACE2组)。细胞经H/R处理后,通过CCK-8法检测细胞活力;RT-PCR及ELISA法检测炎症因子白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)和白介素-1β(IL-1β)水平;比色法检测超氧化物歧化酶(SOD)、丙二醛(MDA)表达水平;Western blotting法检测胱天蛋白酶3(Caspase-3)、B淋巴细胞瘤-2基因(Bcl-2)、Bcl-2关联X蛋白(Bax)、Nrf2、HO-1的蛋白水平。采用Nrf2抑制剂ML385以及HO-1抑制剂SnPPIX抑制Nrf2/HO-1通路,Western blotting法检测Caspase-3、Bcl-2、Bax、Nrf2、HO-1的蛋白表达水平变化,比色法检测SOD和MDA表达变化。 结果 与Control组相比,H/R组细胞活力降低(t=7.58,P<0.001),MDA含量和炎症因子IL-6、TNF-α和IL-1β表达水平以及细胞凋亡相关蛋白Caspase-3、Bax蛋白水平均增加(t_MDA=11.08,P_MDA<0.001;t_PCR-IL-6=5.82,P_PCR-IL6<0.001;t_PCR-TNF-α=7.69,P_PCR-TNF-α<0.001;t_PCR-IL-1β=4.80,P_PCR-IL-1β=0.001;t_ELISA-IL-6=34.11,P_ELISA-IL-6<0.001;t_ELISA-TNF-α=14.12,P_ELISA-TNF-α<0.001;t_ELISA-IL-1β=9.63,P_ELISA-IL-1β<0.001;t_Caspase-3=2.73,P_Caspase-3=0.026;t_Bax=27.75,P_Bax<0.001),SOD活性、Bcl-2和ACE2蛋白水平下降(t_SOD=7.74,P_SOD<0.001;t_Bcl-2=75.49,P_Bcl-2<0.001;t_ACE2=11.41,P_ACE2<0.001)。与H/R组相比,H/R-ACE2组细胞活力增加(t=3.61,P=0.002),MDA含量和炎症因子IL-6、TNF-α和IL-1β表达水平以及细胞凋亡相关蛋白Caspase-3、Bax蛋白水平均下降(t_MDA=6.15,P_MDA<0.001;t_PCR-IL-6=3.34,P_PCR-IL-6=0.006;t_PCR-TNF-α=3.65,P_PCR-TNF-α=0.007;t_PCR-IL-1β=4.06,P_PCR-IL-1β=0.004;t_ELISA-IL-6=14.62,P_ELISA-IL-6<0.001;t_ELISA-TNF-α=10.42,P_ELISA-TNF-α<0.001;t_ELISA-IL-1β=8.65,P_ELISA-IL-1β<0.001;t_Caspase-3=3.74,P_Caspase-3=0.006;t_Bax=30.52,P_Bax<0.001),SOD活性、Bcl-2和ACE2蛋白水平增加(t_SOD=3.58,P_SOD=0.007;t_Bcl-2=63.86,P_Bcl-2<0.001;t_ACE2=58.72,P_ACE2<0.001),Nrf2/HO-1信号通路被激活蛋白水平增加(t_Nrf2=44.55,P_Nrf2<0.001;t_HO-1=14.19,P_HO-1<0.001)。然而ML385和SnPPIX处理会抑制ACE2基因过表达在H/R中HK-2细胞的保护作用(F_Bax=11.02,P_Bax=0.003;F_Bcl-2=21.48,P_Bcl-2<0.001;F_Caspase-3=20.80,P_Caspase-3<0.001;F_SOD=133.49,P_SOD<0.001;F_MDA=14.06,P_MDA=0.001)。 结论 ACE2在HK-2细胞缺氧复氧损伤中具有抑制氧化应激、调节炎症、改善凋亡的作用,Nrf2/HO-1信号通路发挥重要作用。     

右美托咪定调控Nrf2/HO-1通路对H2O2诱导心肌细胞氧化应激损伤的作用研究

目的 探讨右美托咪定调控核因子E2相关因子2(Nrf2)/血红素加氧酶1(HO-1)通路对过氧化氢(H₂O₂)诱导心肌细胞氧化应激损伤的作用。方法 体外培养大鼠H9C2心肌细胞,设置对照组、H₂O₂组、1μmol右美托咪定+H₂O₂组、5μmol右美托咪定+H₂O₂组、10μmol右美托咪定+H₂O₂组。CCK-8法检测各组H9C2细胞增殖情况;酶联免疫吸附试验(ELISA)检测各组H9C2细胞丙二醛(MDA)、超氧化物歧化酶(SOD)水平;实时荧光定量聚合酶链反应(q RT-PCR)检测各组H9C2细胞Nrf2、HO-1 mRNA相对表达量;Western blotting检测各组H9C2细胞Nrf2、HO-1蛋白相对表达量。结果 与对照组比较,H₂O₂组H9C2细胞存活率、SOD水平、Nrf2、HO-1 mRNA及蛋白相对...