Radiobiology of the acute radiation syndrome

Acute radiation syndrome or acute radiation sickness is classically subdivided into three subsyndromes: the hematopoietic, gastrointestinal and neurovascular syndrome but many other tissues can be damaged. The time course and severity of clinical signs and symptoms are a function of the overall body volume irradiated, the inhomogeneity of dose exposure, the particle type, the absorbed dose and the dose rate. Classical pathophysiology explain the failure of each of these organs and the timing of appearance of their signs and symptoms due to radiation-induced cytocidal effects of a great number of parenchymal cells of hierarchically organized tissues. Contemporaneously, many other radiation-induced effects has been described and all of them may lead to tissue injury with their corresponding signs and symptoms that can be expressed after short or long period of time. Radiation-induced multi-organ involvement is thought to be due to radiation-induced systemic inflammatory response mediated by released pro-inflammatory cytokines.     

阿托伐他汀强化降脂治疗急性脑梗死的疗效及对TNF-α、IL-10、IL-18、MMP-9水平的影响

目的:探讨阿托伐他汀强化降脂治疗急性脑梗死(ACI)的临床疗效,并分析其对肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)、白细胞介素-18(IL-18)及基质金属蛋白酶-9(MMP-9)水平的影响。方法:选取2015年3月-2016年12月我院收治的82例ACI患者,采用随机数字表法随机分为强化组(n=41)与常规组(n=41)。在常规治疗的基础上,常规组患者给予20 mg/次的阿托伐他汀治疗,强化组患者给予40 mg/次的阿托伐他汀治疗,两组均连续治疗8w。治疗结束后对比两组患者的临床疗效,对比两组患者治疗前后总胆固醇(TC)、三酰甘油(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、组织型纤溶酶原激活物(t-PA)、血浆纤溶酶原激活物抑制剂-1(PAI-1)、血浆纤维蛋白原(FIB)、TNF-α、IL-10、IL-18、MMP-9水平。结果:强化组与常规组患者的总有效率分别为95.12%、80.49%,与常规组对比,强化组患者的临床总有效率明显升高(P0.05);两组患者治疗后的TC、TG、LDL-C、PAI-1、FIB、TNF-α、IL-18、MMP-9水平均较治疗前显著降低,HDL-C、t-PA、IL-10水平均显著升高(P0.05),且治疗后强化组患者的TC、TG、LDL-C、PAI-1、FIB、TNF-α、IL-18、MMP-9水平均低于常规组,HDL-C、t-PA、IL-10均高于常规组(P0.05)。结论:阿托伐他汀强化降脂治疗ACI疗效较好,能够显著改善患者血脂、纤溶系统及炎症因子相关指标水平,具有降脂、调节纤溶活性及抑制炎症的作用。     

Oxygen-derived free radicals and hemolysis during open heart surgery

Reperfusion injury occurs during open-heart surgery after prolonged cardioplegic arrest. Cardiopulmonary bypass also is known to cause hemolysis. Since reperfusion of ischemic myocardium is associated with the generation of oxygen free radicals, and since free radicals can attack a protein molecule, it seems reasonable to assume that hemolysis might be the consequence of free radical attack on hemoglobin protein. The results of this study demonstrated that reperfusion following ischemic arrest caused an increase in free hemoglobin and free heme concentrations, simultaneously releasing free iron and generating hydroxyl radicals. In vitro studies using pure hemoglobin indicated that superoxide anion generated by the action of xanthine oxidase on xanthine could release iron from the heme ring and cause deoxygenation of oxyhemoglobin into ferrihemoglobin. This study further demonstrated that before the release of iron from the heme nucleus, oxyhemoglobin underwent deoxygenation to ferrihemoglobin. The released iron can catalyze the Fenton reaction, leading to the formation of cytotoxic hydroxyl radical (OH·). In fact, the formation of OH. in conjunction with hemolysis occurs during cardiac surgery, and when viewed in the light of the in vitro results, it seems likely that oxygen-derived free radicals may cause hemolysis during cardiopulmonary bypass and simultaneously release iron from the heme ring, which can catalyze the formation of OH·.     

急性心肌梗死患者肠道优势菌群分析

目的探讨急性心肌梗死患者肠道优势菌群的改变及其与疾病严重程度的关系。方法共筛选急性心肌梗死患者71名及正常健康体检者33名,急性心肌梗死患者根据是否心衰分为急性心肌梗死组36名和急性心肌梗死伴泵衰竭组35名,所有入选者收集大便及血清标本,分别采用qPCR及化学发光仪测定肠道优势菌群改变和血清脑钠肽前体及肌钙蛋白水平。结果急性心肌梗死患者肠道优势菌群显著改变,肠道肠杆菌以及肠球菌细菌数量较对照组显著增加,均与脑钠肽前体、肌钙蛋白、Killip分级显著正相关,而双歧杆菌、乳酸杆菌等细菌数量显著降低,与脑钠肽前体、肌钙蛋白、Killip分级显著负相关。结论急性心肌梗死患者呈现典型的肠道菌群紊乱,且与患者疾病严重程度相关。     

急性轻中度缺氧EEG信号的复杂度研究

建立了一个急性高空缺氧实验模型,记录了四种不同高度条件下从缺氧前(正常呼吸)到缺氧后30分钟时的EEG,分析了其复杂度。发现缺氧引起复杂度明显变化,随时间和高度增加,一定程度缺氧可使EEG复杂度低于正常。表明EEG复杂度对脑缺氧较为敏感,可用于缺氧程度进行评估,有望成为临床诊断的一个指标。     

血清胃泌素变化与急性胃粘膜病变关系的研究

对大白鼠血清中胃泌素水平的变化与急性胃粘膜病变的关系进行了初步的研究,结果表明以消炎痛为诱因引起的急性胃粘膜病变大白鼠血清胃泌素水平明显增高。而维酶素可以抑制因消炎痛引起的急性胃粘膜病变时血清胃泌素的释放,对胃粘膜具有保护作用。     

Acute phase response to recombinant interleukin-6 and macrophage- and fibroblast-derived crude cytokine preparations in primary cultures of mouse hepatocytes

A number of acute phase proteins were determined by electroimmunoassay in media from CBA mouse hepatocytes cultured for 2 days with human recombinant IFN beta 2/IL-6, as well as with conditioned media from LPS-stimulated rat macrophages, and of murine L fibroblasts. It was found that human recombinant IL-6 caused three-fold increase in secretion of fibrinogen, while haptoglobin, complement C3 and transferrin were increased respectively, to 168 per cent, 151 per cent, and 145 per cent of the control. DEX(10(-7) M) in DMEM supplemented with 5 per cent FCS, enhanced the IL-6 effect on the three positive acute phase proteins. IL-6 elevated haptoglobin mRNA in mouse hepatocytes to a degree comparable with the concentration of the protein in the culture medium. The effect of conditioned media from murine fibroblasts and peritoneal rat macrophages was generally similar to that of recombinant IL-6. However, both natural preparations of the cytokines caused decrease in albumin and alpha-1-proteinase inhibitor secretion.     

Serological differentiation of acute and chronic schistosomiasis using Schistosoma mansoni recombinant protein RP26

We obtained a recombinant protein encoded by Schistosoma mansoni gene which was able to differentiate acute from chronic schistosomiasis when applied as antigen in enzyme-linked immunosorbent assay (ELISA). A cDNA clone encoding a 26 kDa recombinant protein (RP26) was selected by screening of an adult worm S. mansoni λZAP expression library with rabbit sera produced against PIII, an adult worm protein fraction already known to possess protective and immunomodulating effects. The clone cDNA presented 99% identity with S. mansoni Sm22.3 gene. We assayed IgG reactivity of sera from 18 patients with acute, 25 patients with chronic S. mansoni infection and 20 uninfected donors with RP26 in ELISA. Our results showed that 89% of sera were positive in acute schistosomiasis group, and only 26% in chronic group, without false-positive reactions in uninfected group. In mice the immune response to RP26 increased up to week 9 after infection and then diminished. We proposed that production of antibodies binding to RP26 stopped at the chronic stage of disease. The testing of sera from eight other parasitic infections with RP26 revealed no positive reactions in majority of sera. However, we observed low positive reaction in sera from 20% of leishmaniasis patients. Our results indicate that a recombinant protein RP26 can be used as immunodiagnostic reagent for detection of acute phase of schistosomiasis mansoni.     

Development of 5-hydroxypyrazole derivatives as reversible inhibitors of lysine specific demethylase 1

A series of reversible inhibitors of lysine specific demethylase 1 (LSD1) with a 5-hydroxypyrazole scaffold have been developed from compound 7, which was identified from the patent literature. Surface plasmon resonance (SPR) and biochemical analysis showed it to be a reversible LSD1 inhibitor with an IC₅₀ value of 0.23 µM. Optimisation of this compound by rational design afforded compounds with K_d values of <10 nM. In human THP-1 cells, these compounds were found to upregulate the expression of the surrogate cellular biomarker CD86. Compound 11p was found to have moderate oral bioavailability in mice suggesting its potential for use as an in vivo tool compound.