Increased monocyte-dependent suppression of polyclonal activation of B lymphocytes from cystinotic children

In infantile cystinosis the amino acid cystine preferentially accumulates in phagocytic cells, polymorphonuclear leucocytes (PMN) and monocytes, rather than in lymphocytes. We previously described functional abnormalities in the oxidative metabolism and locomotion of cystinotic PMN and monocytes. The present study shows an abnormal lymphocyte polyclonal activation as evidenced by a decreased immunoglobulin (Ig) production and generation of Ig-containing cells (ICC) in cultures of peripheral blood mononuclear cells (PBMC) from cystinotic children upon stimultion with pokeweed mitogen andStaphylococcus aureus Cowan I. However, monocyte depletion from cystinotic PBMC fully reconstituted Ig production and ICC generation, indicating: (1) the presence of an increased monocyte-dependent suppression on lymphocyte polyclonal activation, and (2) that the intrinsic ability of cystinotic lymphocytes to respond to polyclonal stimulation was preserved. The increased cystinotic monocytedependent suppressive effect was not mediated by prostaglandin E₂ (PGE₂) since its production by cystinotic PBMC upon polyclonal activation was not different from that of controls. In addition, the sensitivity of cystinotic lymphocytes to the immunosuppressive effect of varying concentrations of exogenous PGE₂ was similar to that of controls. Finally, indomethacin and 2-mercaptoethanol, two agents able to scavenge hydroxyl (OH) radicals, restored Ig production by cystinotic PBMC, suggesting a role for reactive oxygen species in the increased cystinotic monocyte-dependent suppression.     

Comparison of the lactate-pyruvate ratio during labour and delivery in singleton and twin pregnancy

Oxygen utilisation at the tissue level was investigated by the use of lactate-pyruvate (LP) ratio in forty women; twenty with term twin pregnancy, with a matched controlled group of twenty women with term singleton pregnancy. The lactate-pyruvate ratio in twin pregnancy was significantly higher than in singleton pregnancy at term (p < 0.05). There was also significantly higher LP ratio in advanced labour in twin pregnancy than in singleton pregnancy (p < 0.001). Similarly, the venous cord blood LP ratio of twin II was higher than in twin I. Our findings have thus demonstrated more marked anaerobic metabolism in twin pregnancy than in singleton pregnancy. Secondly, the second twin is more involved in anaerobic metabolism as a result of relative oxygen deficiency, than twin I. This may to some extent account for the higher morbidity and mortality in twin pregnancy, compared to singleton pregnancy, and in twin II compared to twin I. Received: 20 March 1995 / Accepted: 25 July 1995     

Hyperbaric oxygenation induced tolerance against focal cerebral ischemia in mice is strain dependent

SV129 or C57BL/6 mice were exposed to hyperbaric oxygenation (HBO, 5 days, 1 h every day, 100% O(2) at 3 atm absolute). One day after the 5th HBO session focal cerebral ischemia was induced. In SV129 mice, HBO induced tolerance against permanent focal cerebral ischemia (n=42, mean infarct volume reduction 27%, P=0.001), but not against transient (30 or 60 min) focal cerebral ischemia. In the C57BL/6 strain of mice, HBO did not induce tolerance against focal cerebral ischemia, even when the duration of ischemia or the HBO protocol were modified. For the first time we demonstrate that HBO can induce tolerance to focal cerebral ischemia, but this effect is strain dependent.     

糖尿病早期内耳损伤听力学改变的实验研究

目的研究糖尿病内耳损伤早期的听力学改变及其机制。方法建立糖尿病动物模型,每日检测动物血糖,持续2周。实验前后检测ABR及DPOAE,2周后检测血脂、超氧化物岐化酶（SOD）、谷胱甘肽过氧化物酶（GSHPx）、血清丙二醛（MDA）,并与对照组比较。结果模型组大鼠的血糖、血脂增高,GSH-Px的活性下降,ABR阈值无显著变化,DPOAE的反应幅值下降,与正常组比较差异有统计学意义（P〈0．05）。结论糖尿病造成大鼠内耳损害的机制与机体代谢紊乱引起内耳毛细胞的氧化损伤有关;这种损伤所致的耳声发射的异常改变早于听性脑干反应异常的出现。     

Analysis of the metabolic footprint and tissue metabolome of placental villous explants cultured at different oxygen tensions reveals novel redox biomarkers

Pre-eclampsia (PE) is a multi-system disorder of pregnancy hypothesised to arise from circulating factors derived from an unhealthy placenta. Some changes in placental phenotype seen in PE can be reproduced by culture in altered oxygen (O(2)) tension. Currently, these circulating factors are unidentified, partly due to the complexity of maternal plasma. Investigation of factors released from placental tissue provides a potential method to identify bioactive compounds. Experimental strategies to study compounds present in a biological system have expanded greatly in recent years. Metabolomics can detect and identify endogenous and secreted metabolites. We aimed to determine whether metabolites could be identified in placental cultures with acceptable experimental variability and to determine whether altered O(2) tension affects the composition of the placental metabolome. In this study we used gas-chromatography-mass spectroscopy to determine the presence of metabolites in conditioned culture medium (CCM) and tissue lysates of placental villous explants cultured in 1, 6 and 20% atmospheric O(2) for 96h. This experimental strategy had an intra-assay variation of 6.1-11.6%. Intra and inter-placental variability were 15.7-35.8% and 44.8-46.2% respectively. Metabolic differences were identified between samples cultured in 1, 6 and 20% O(2) in both CCM and tissue lysate. Differentially expressed metabolites included: 2-deoxyribose, threitol or erythritol and hexadecanoic acid. We conclude that metabolomic strategies offer a novel approach to investigate placental function. When conducted under carefully controlled conditions, with appropriate statistical analysis, metabolic differences can be identified in placental explants in response to altered O(2) tension. Metabolomics could be used to identify changes in conditions associated with placental pathology.     

严重创伤后氧对T细胞功能的影响

目的 探讨严重创伤后病人T淋巴细胞转化活性及CD4 T、CD8 T细胞活性变化,CTLA-4分子水平在严重创伤转归、干预治疗等方面的意义.方法 将133例病人分为创伤对照组46例、高流量吸氧组44例、高压氧组43例,创伤对照组患者入院后给予常规治疗;高流量吸氧组患者辅以5 L/min,120 min/d吸氧治疗;高压氧组患者辅以高压氧治疗(压力2 ATA,60 min/d).于3、7 d时间点,对各组分别进行T淋巴细胞转化活性、T淋巴细胞亚群及CTLA-4分子水平的测定.结果 与创伤对照组比较,高流量吸氧组和高压氧组患者的T淋巴细胞转化活性增高,CD4 T细胞数明显增多(P＜0.01),CD4 /CD8 细胞比值明显增加(P＜0.01),T细胞表面和总CTLA-4分子表达明显降低(P＜0.01);与高流量吸氧组相比,高压氧组患者的T淋巴细胞转化活性增高,CD4 T细胞数明显增多(P＜0.05),CD4 /CD8 细胞比值明显增加(P＜0.01),T细胞表面和总CTLA-4分子表达降低(P＜0.05).结论 氧能够明显提高T淋巴细胞转化活性,使CD4 T细胞增多,CD4 /CD8 细胞比值明显增加,并且明显降低T细胞表面和总CTLA-4分子的表达.     

早产儿缺氧缺血性脑病的MRI征像分析

目的:探讨分析早产儿缺氧缺血性脑病的MRI表现及其病理生理。方法:132例临床诊断为新生儿缺氧缺血性脑病的早产儿,常规行T1WI、T2WI、DWI、FLAIR扫描。结果:临床表现均考虑HIE,MRI表现皮层及皮层下出血、深部白质出血、脑室旁出血、脑室内出血、脑室旁软化灶。结论:MRI对早产儿HIE具有特征性表现,对早产儿HIE的早期诊断有重要意义。     

全麻快诱导期非加压通气的可行性

目的观察丙泊酚-爱可松-瑞芬太尼快诱导期非正压通气的可行性及对急性胃扩张的预防效果。方法20例择期全麻病人入手术室即作动脉血气分析,高流量(8~10L/m in)吸氧5m in后静注丙泊酚(2mg/kg)-爱可松(0.8mg/kg)-瑞芬太尼(1μg/kg)序贯快诱导(60 s内注射完毕),60 s后气管插管。插管成功即刻再进行动脉血气分析。诱导插管期间任由患者进入无呼吸状态而不给予正压辅助通气。结果各病人诱导后插管条件满意,平均插管耗时27.45 s。诱导插管后患者的PaO2、PaCO2均上升,与基础值相比分别为(242±111)Vs(93±10)mm Hg(P<0.01)和(45±8)Vs(39±4)mm Hg(P<0.01),无急性胃扩张发生。结论经5m in的高流量纯氧预吸后,丙泊酚-爱可松-瑞芬太尼快诱导插管期无通气并无低氧、高碳酸血症的发生,且可有效防止诱导期急性胃扩张发生。     

Mechanical efficiency of the left ventricle as a function of preload,afterload, and contractility

Summary We have recently shown that the mechanical efficiency of the contractile machinery of the canine left ventricle is constant at 30%–50%, independent of its loading, heart rate, and inotropic conditions. In contrast, the conventional mechanical efficiency of the ventricle is known to vary between 0 and 30%, depending on these conditions. In this study, we derived an equation for the conventional mechanical efficiency as a function of ventricular preload, afterload, and contractility, based on the constant mechanical efficiency of the contractile machinery. In deriving this equation, we fully utilized our new concept of the total mechanical energy of the left ventricle, i.e., systolic pressure-volume area, and our recent findings of the linear relationship between left ventricular oxygen consumption and the systolic pressure-volume area as well as the dependence of this relation on the ventricular inotropic state. As a result, the conventional mechanical efficiency of the left ventricle was found to change between 0 and 25% as an explicit function of these cardiodynamic and inotropic conditions. Using this function, we obtained combinations of loading and inotropic conditions to maximize the conventional mechanical efficiency of the left ventricle.