On the Mechanism of the Radioprotective Action of Cyanide

Summary

The mechanism of the radioprotective action of cyanide has been investigated with rat-thymocyte suspensions, cultured human-kidney cells and with mice.

Cyanide does not protect cells in vitro. In the thymocyte system, cyanide has instead a slight radiosensitizing action. The presence of cyanide after the irradiation causes an inhibition of the development of eosin permeability.

In mice, cyanide produces a hypoxia of the spleen and bone-marrow. This hypoxia explains the protection against a lethal dose of x-rays.     

基于蒙特卡罗模拟的小动物质子CT最优射束能量

目的 观察基于蒙特卡罗模拟的小动物质子CT （PCT）的最优射束能量。方法 采用蒙特卡罗模拟建立PCT系统,分别以不同能量质子束对体模1、2进行扫描,并以滤波反投影法重建图像,观察其中不同材料质子的相对阻止本领（RSP）值、重建误差、空间分辨率、信号噪声比（SNR）及对比噪声比（CNR）,评估图像质量,筛选最优质子射束能量。结果 重建图像中,特氟龙、聚丙烯及骨骼等效材料的RSP的相对误差均随质子能量增高而先降后升,于质子能量为130 MeV时最小,分别为0.76%、0.08%及0.05%。体模1内4种插件的SNR和CNR均随质子能量增高而降低。重建图基本无法分辨体模2内直径0.2 mm铝插件,质子能量较低时可分辨直径0.4 mm铝插件;不同质子能量下均可分辨直径0.8 mm铝插件,且空间分辨率随质子能量增高而提升,质子能量大于130 MeV后变化趋缓。结论 以蒙特卡罗模拟的小动物PCT平台的最优成像质子射束能量为130 MeV。     

High pH accelerates GABA deactivation on perch-rho1B receptors

The ionotropic GABA(C) receptor, formed by GABA rho subunits, is known to be modulated by a variety of endogenous compounds, as well as by changes in pH. In this study, we explore the proton sensitivity of the GABA rho subunits cloned from the perch retina, and report a novel action of high pH on the homomeric receptor formed by one of the GABA rho subunits, the perch-rho(1B) subunit. Raising extracellular pH to 9.5 significantly accelerated GABA deactivation responses elicited from oocytes expressing the perch-rho(1B) subunit, and reduced its sensitivity to GABA. The change in the kinetics of the GABA-offset response occurred without altering the maximum response amplitude, and the reduced GABA sensitivity was independent of membrane potential. Although acidification of the extracellular solution also accelerated GABA deactivation for all other GABA rho receptors examined in this study, the effects of high pH were unique to the homomeric receptor formed by the perch-rho(1B) subunit. In addition, we found that, unlike the effects on the response to the naturally occurring full agonist GABA, the responses elicited by partial agonists (imidazole-4-acetic acid (I4AA) and beta-alanine) in the presence of the high pH solution showed a significant reduction in the maximum response amplitude. When considered in terms of a model describing the activation of GABA(C) receptors, in which pH can potentially affect either the binding affinity or the rate of channel closure, the results were consistent with the view that external alkalization reduces the gating efficiency of the receptor. To identify the proton sensitive domain(s) of the perch-rho(1B) receptor, chimeras were constructed by domain swapping with other perch-rho subunits. Analysis of the pH sensitivities of the various chimeric receptors revealed that the alkaline-sensitive residues are located in the N-terminal region of the perch-rho(1B) subunit.     

帕金森病患者壳核质子磁共振波谱研究

目的利用质子磁共振波谱(1H MRS)技术研究帕金森病(PD)患者壳核的代谢变化及意义.方法PD患者46例和正常对照30例行1H MRS检查,测定双侧壳核的N-乙酰天门冬氨酸/肌酸(NAA/Cr)、N-乙酰天门冬氨酸/胆碱复合物(NAA/Cho)和胆碱复合物/肌酸(Cho/Cr)比值.结果早期PD患者有症状侧肢体和中晚期PD患者症状严重侧肢体的对侧壳核NAA/Cr比值低于对照组(P＜0.05),未予多巴胺制剂治疗的PD患者症状严重侧肢体的对侧壳核NAA/Cr比值低于对照组(P＜0.05).结论1H MRS检测到壳核的NAA/Cr比值降低,有助于PD以及早期PD的诊断;壳核NAA/Cr比值受多巴胺制剂治疗的影响,NAA/Cr可作为纹状体神经元功能异常的可逆性标志.     

Synaptic signals mediated by protons and acid‐sensing ion channels

Extracellular pH changes may constitute significant signals for neuronal communication. During synaptic transmission, changes in pH in the synaptic cleft take place. Its role in the regulation of presynaptic Ca²⁺ currents through multivesicular release in ribbon‐type synapses is a proven phenomenon. In recent years, protons have been recognized as neurotransmitters that participate in neuronal communication in synapses of several regions of the CNS such as amygdala, nucleus accumbens, and brainstem. Protons are released by nerve stimulation and activate postsynaptic acid‐sensing ion channels (ASICs). Several types of ASIC channels are expressed in the peripheral and central nervous system. The influx of Ca²⁺ through some subtypes of ASICs, as a result of synaptic transmission, agrees with the participation of ASICs in synaptic plasticity. Pharmacological and genetical inhibition of ASIC1a results in alterations in learning, memory, and phenomena like fear and cocaine‐seeking behavior. The recognition of endogenous molecules, such as arachidonic acid, cytokines, histamine, spermine, lactate, and neuropeptides, capable of inhibiting or potentiating ASICs suggests the existence of mechanisms of synaptic modulation that have not yet been fully identified and that could be tuned by new emerging pharmacological compounds with potential therapeutic benefits.     

轻度认知功能损害氢质子磁共振波谱变化及其意义

目的:研究轻度认知功能损害(mild cognitive impairment,MCI)脑内代谢变化及其与认知功能间的关系,寻求诊断MCI之客观指标,并探讨其对防治老年性痴呆(Alzheimet's disease,AD)之重要意义.方法:选择20例MCI患者,按照1:1配对,挑选20例健康志愿者作为对照组,利用氢质子磁共振波谱(1 H-magnetic resonance spectroscopy,1H-MRS)的方法,分别检测额叶、颞叶海马区域NAA,ml及Cho等代谢产物波峰的峰高,并以Cr峰高作为标准,计算各代谢产物与其比值,比较两组间的差别;同时,对MCI组的MMSE评分和NAA/Cr,ml/Cr及Cho/Cr进行相关分析.结果:MCI组患者脑内额叶和颞叶海马区域NAA/Cr较正常对照组显著下降,而ml/Cr和Cho/Cr与对照组间无显著差异.MCI组MMSE评分与额叶和海马区域NAA/Cr间均呈正相关关系,与nd/Cr及Cho/Cr间均无显著相关关系.结论:利用1H-MRS可以检测MCI患者脑内代谢变化,为MCI之诊断提供客观指标,且NAA/Cr变化可作为认知损害程度的客观指标,对AD早期防治具有重要意义.     

Proton therapy for central nervous system tumors in children

Proton therapy is a form of particle therapy with physical properties that provide a superior dose distribution compared to photons. The ability to spare healthy, developing tissues from low dose radiation with proton therapy is well known. The capability to decrease radiation exposure for children has been lauded as an important advance in pediatric cancer care, particularly for central nervous system (CNS) tumors. Favorable clinical outcomes have been reported and justify the increased cost and burden of this therapy. In this review, we summarize the current literature for proton therapy for pediatric CNS malignancies, with a focus on clinical outcomes to date.     

Relative biological effectiveness of simulated solar particle event proton radiation to induce acute hematological change in the porcine model

The present study was undertaken to determine relative biological effectiveness (RBE) values for simulated solar particle event (SPE) radiation on peripheral blood cells using Yucatan minipigs and electron-simulated SPE as the reference radiation. The results demonstrated a generally downward trend in the RBE values with increasing doses of simulated SPE radiation for leukocytes in the irradiated animals. The fitted RBE values for white blood cells (WBCs), lymphocytes, neutrophils, monocytes and eosinophils were above 1.0 in all three radiation dose groups at all time-points evaluated, and the lower limits of the 95% confidence intervals were > 1.0 in the majority of the dose groups at different time-points, which together suggest that proton-simulated SPE radiation is more effective than electron-simulated SPE radiation in reducing the number of peripheral WBCs, lymphocytes, neutrophils, monocytes and eosinophils, especially at the low end of the 5–10 Gy dose range evaluated. Other than the RBE values, the responses of leukocytes to electron-simulated SPE radiation and proton-simulated SPE radiation exposure are highly similar with respect to the time-course, the most radiosensitive cell type (the lymphocytes), and the shape of the dose–response curves, which is generally log-linear. These findings provide additional evidence that electron-simulated SPE radiation is an appropriate reference radiation for determination of RBE values for the simulated SPE radiations, and the RBE estimations using electron-simulated SPE radiation as the reference radiation are not complicated by other characteristics of the leukocyte response to radiation exposure.