The importance of free hydroxyl radicals to hypoxia preconditioning

Hypoxia preconditioning states that a sublethal hypoxia period will afford neuroprotection against a second harmful event. In our experiments, we carried out a procedure for the development of hypoxia preconditioning in adult male Wistar rats using hypoxic exposure (9% O(2); 91% N(2)) for 1 h. The protection against pentylenetetrazol (PTZ)-induced seizures was studied. For this, rats were tested by a single injection of PTZ (55 mg/kg i.p.) on days 1-21 after hypoxia exposure. The hypoxia exposure significantly prevented the development of acute PTZ convulsion at different times after hypoxia. The present study was designed to determine the effect of N-t-butyl-alpha-phenylnitrone (PBN), an electron-trapping agent and free radical scavenger, on hypoxia preconditioning against PTZ seizures 7 days after hypoxia exposure. PBN abolished the protective action of hypoxia exposure. The generation of free hydroxyl radicals in the brains of animals exposed to hypoxia was determined in a second experiment. For this purpose, the rats were i. p. pretreated with 30 mg/kg PBN and NaCl, respectively, 20 min before the start of hypoxia exposure. Forty-five minutes later the rats were i.p. injected with 300 mg/kg sodium salicylate and once again exposed to hypoxia for 15 min. Immediately after that the animals were decapitated and the free hydroxyl radicals and the salicylate content were estimated in the whole brain without cerebellum. Hypoxia preconditioned animals pretreated with NaCl showed a significantly higher extent of free hydroxyl radicals in the brain compared with PBN-injected preconditioned animals and with naive and sham exposed controls. The results pointed out that the generation of free reactive oxygen species under hypoxic conditions in the brain is involved in the development of the hypoxic preconditioning phenomenon.     

CoQ10 fails to protect brain against focal and global ischemia in rats

OBJECTIVE: Release of oxygen free radicals occurs following cerebral ischemia. Studies show that oxygen free radicals mediate ischemic brain injury. CoQ10 is a potent free radical scavenger and may offset brain injury associated with reperfusion. We tested exogeneous CoQ10 as a neuroprotectant in rats following both global and focal ischemic insults. METHODS: Rats were subjected to either 4-vessel occlusion ischemia (4-VO, 10 min occlusion, 7-day survival) or middle cerebral artery occlusion (MCAO, 120 min-occlusion, 22.5 h survival). Regional cerebral blood flows (rCBF) and physiological variables such as blood pressure, pO2, pCO2, plasma glucose and hematocrit were monitored and measured in focal ischemia. The animals were randomized to receive treatments of either phosphate buffered saline (PBS) vehicle or CoQ10 following global or focal ischemia. Injection times were at the end of ischemia and 3 h later for both models of ischemia. Histological outcomes are expressed as a percentage of hippocampal CA(1) cell injury in global ischemia or percentage of cortical infarct over that of non-ischemic hemisphere in focal ischemia. RESULTS: In global ischemia, animals treated with PBS vehicle and CoQ10 had 86+/-5% (n=8) and 83+/-10% (n=8), respectively, of hippocampal CA(1) cell injury (P>0.05). The percentage of infarct volumes in animals following focal ischemia were 23+/-9% (control, n=10) and 25+/-9% (CoQ10, n=10). There were no temperature or physiological differences between the two treatment groups. CONCLUSION: Acute treatment with CoQ10 via intraperitoneal injection does not prevent neuronal injuries following global and focal ischemia.     

人工耳蜗植入后不同言语处理器编程方案的比较

目的　了解和认识体佩式 (SPrint)和耳背式言语处理器 (ESPrit 3G)在调试中的不同特点 ,以便更好地进行人工耳蜗调式。方法　对 9例年龄 2～ 5 4岁的全聋患者于手术后 6～ 2 4个月由使用SPrint转换使用ESPrit 3G ,比较使用不同言语处理器调试所创建的电听力图之阈值 (thresholdlevel,T -L)和舒适阈 (comfortablelevel,C -L)、以及在ESPrit 3G使用不同程序时的声场测试和问卷调查结果 ,并进行统计学分析。结果　使用由SPrint获得的程序佩戴ESPrit 3G ,4例患者 (1组 )感觉聆听效果满意 ,与以往佩戴SPrint无差异。有 5例患者 (2组 )从不同言语处理器所获得的T -L和C -L有显著差异 (P <0 .0 1) ;使用不同的编程佩戴ESPrit3G进行声场 (啭音 )听阈测试 ,结果有显著差异 (P <0 .0 1) ;问卷调查显示使用经ESPrit3G直接调试获得的程序较使用由SPrint转换而来的程序有更好的聆听效果。 1组与使用ESPrit 3G调试获得程序的 2组的声场测试结果无差异 (P >0 .0 5 )。 1组与使用由SPrint转换而来程序的 2组的声场测试结果有显著差异 (P <0 .0 1)。结论　由佩戴SPrint转为使用ESPrit3G时 ,部分患者直接使用由SPrint转化而来的程序可能存在音量感受不足的情况 ,因此为了使患者获得更好的聆听效果 ,应经ESPrit 3G重新进行     

患者接受医院免费健康教育处方状况分析

目的　了解来北京大学第一医院就诊者及其家属对《健康教育处方》的认同状况。方法　对摆放健康教育处方前来院就诊者及其陪同家属 3 98人和摆放《健康教育处方》后主动索取《健康教育处方》的 5 49人进行问卷调查。结果　《健康教育处方》摆放前 ,97 74%的人认为候诊等待时烦躁 ,92 2 1 %的人抱怨缺乏阅读材料 ,97 99%的赞成摆放《健康教育处方》 ;摆放《健康教育处方》后 ,3 7 70 %的人候诊等待时感到烦躁 ,仅 9 47%的人抱怨缺乏阅读材料 ,98 1 8%的人赞成摆放《健康教育处方》。结论　在医院发放《健康教育处方》是可行的 ,由制药厂赞助《健康教育处方》印制的方式受到大多数就诊者的认可     

富勒烯和富勒醇的生物学和生物医学应用研究

介绍富勒烯C60和富勒醇C60(OH)n(n=6-24)的生物学和生物医学应用。C60可抑制半胱氨酸蛋白酶和丝氨酸蛋白酶的活性，它以强憎水作用结合于HIVP(人体免疫缺损病毒蛋白酶)的空穴，可抑制HIVP的活性，可使氧分子转化为活性氧和超氧自由基，切割DNA。富勒醇可抑制小鼠大动脉平滑肌细胞生长，但促进HL-60细胞的生长代谢。C60能清除自由基，在光照和避光条件下具有诱导癌细胞凋亡的能力。     

医院获得性肺炎克雷伯菌性肺炎患者脂质过氧化损伤的研究

目的探讨医院获得性肺炎克雷伯菌性肺炎患者体内的氧自由基损伤. 方法对呼吸加强病房20例医院获得性肺炎克雷伯菌性肺炎患者血清脂质过氧化氢(LHP)水平、血清谷胱甘肽过氧化物酶(GSH-PX) 及血清3种超氧化物歧化酶(SOD)进行测定, 并与对照组进行比较. 结果克雷伯菌性肺炎组LHP明显高于健康对照组, 两组比较差异非常显著(t=7.8901, P<0.01);GSH-PX水平明显低于对照组, 两组比较差异非常显著(t=9.9810, P<0.01);SOD T、SOD Cu-Zn、SOD Mn水平明显低于对照组, 两组比较差异非常显著(t=7.8546, t=10.3378, t=5.2179, 均P<0.01). 结论医院获得性肺炎克雷伯菌性肺炎患者体内存在由自由基介导的脂质过氧化损伤,这种脂质过氧化损伤参与了肺炎克雷伯菌性肺炎的病理过程;在治疗中合理使用自由基清除药物可能提高临床疗效.     

Diagnóstico y seguimiento de los pacientes con hipotiroidismo congénito diagnosticados por cribado neonatal

The screening program of congenital hypothyroidism (CH) is probably one of the best achievements in paediatrics. Thyroid hormones are essential for brain development and brain maturation that continue through the neonatal period. Hypothyroidism that begins in the first months of life causes irreversible damage to the central nervous system, and is one of the most frequent and preventable causes of mental retardation. As children with congenital hypothyroidism are born with a normal appearance, analytical studies are required to immediately start the appropriate therapy.This article analyses the aims, diagnostic procedures, tests required, aetiology, and differential diagnosis in this disorder. Especially relevant is to perform frequent monitoring to ensure dose adjustments of L-Thyroxine therapy, avoiding infra- or supra-dosing that negatively affects neurosensory functions. Re-evaluation of the aetiology permanent vs transient hypothyroidism is always recommended after 3 years of chronological age.The relevance of this screening program should be widely discussed in paediatrics. The main objective is to avoid cerebral damage in these patients, and has been highly successful and economically beneficial.Other aspects are required to optimise patient outcomes, to perform all the controls according to the recommendations and to include, in the near future, the diagnosis of central hypothyroidism. Implementation of this program is necessary to progress in accordance with current scientific knowledge.     

Curcumin/turmeric solubilized in sodium hydroxide inhibits HNE protein modification--an in vitro study

Free radical mediated lipid peroxidation has been implicated in multiple diseases. A major oxidation by-product of this deleterious process is 4-hydroxy-2-nonenal (HNE). HNE is cytotoxic, mutagenic and genotoxic and is involved in disease pathogenesis. Curcumin, a non-steroidal anti-inflammatory agent (occurring as the yellow pigment found in the rhizomes of the perennial herb Curcuma longa known as turmeric), has emerged as the newest "nutraceutical" agent that has been shown to be efficacious against colon cancer and other disorders, including correcting cystic fibrosis defects. Since curcumin has been reported to have anti-oxidant properties we hypothesized that it will inhibit HNE-modification of a protein substrate. Using an ELISA that employed HNE-modification of solid phase antigen following immobilization, we found that the curcumin solubilized in dilute alkali (5mM sodium hydroxide, pH 11) inhibited HNE-protein modification by 65%. Turmeric also inhibited HNE-protein modification similarly (65%) but at a much lower alkali level (130muM sodium hydroxide, pH 7.6). Alkali by itself (5mM sodium hydroxide, pH 11) was found to enhance HNE modification by as much as 267%. Curcumin/turmeric has to inhibit this alkali enhanced HNE-modification prior to inhibiting the normal HNE protein modification induced by HNE. Thus, inhibition of HNE-modification could be a mechanism by which curcumin exerts its antioxidant effects. The pH at which the inhibition of HNE modification of substrate was observed was close to the physiological pH, making this formulation of curcumin potentially useful practically.     

黄花倒水莲抗氧化活性研究

目的:阐明黄花倒水莲(PolygalafallaxHemsl.[P.aureocaudaDumn])的抗氧化活性及有效部位,为进一步的活性追踪及临床应用提供理论依据。方法:从广西采集黄花倒水莲的根部分,经植化手段分离得到7个化学性质不同的组分(PFE1、PFE2、PFE3、PFB4、PFB5、PFB6、PFW7)。用比色法研究了各组分还原三价铁离子及清除脂性自由基DPPH能力,采用化学发光法观察各组分清除羟自由基和超氧阴离子的活性。结果:PFE3、PFB4对DPPH、羟自由基、超氧阴离子的清除作用EC50分别为92·44,42·29,5·50;96·33,38·26,6·21μg·mL-1。结论:黄花倒水莲各组分均有一定的清除自由基作用,这可以用来解释其在传统应用中的抗炎、抗衰老作用。     

五味余甘子散对大鼠心肌缺血再灌损伤的保护作用

目的探讨藏方五味余甘子散对心肌缺血再灌损伤大鼠的保护作用。方法将96只SD大鼠随机均分成五味余甘子散高、中、低剂量组及伪手术组、模型组和阳性对照组,连续给药10 d,在末次给药24 h后,进行造模,结扎左冠前室间支30min,复灌40 min。测定血清中乳酸脱氢酶(LDH)、肌酸激酶(CK)的含量及心肌组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)的活性和丙二醛(MDA)的含量,并比较各组心肌的超微结构变化。结果五味余甘子散能显著降低血清中LDH和CK的含量,同时能提高心肌组织中SOD、GSH-Px的活性,降低MDA的活性。结论五味余甘子散对大鼠心肌缺血再灌损伤有保护作用,其机制可能与抑制自由基相关酶有关。