Proline reduces brain cytochrome c oxidase: prevention by antioxidants

In the present study, we initially investigated the in vivo (acute and chronic) and in vitro effects of proline on cytochrome c oxidase (complex IV) activity in rat cerebral cortex to test the hypothesis that proline might alter energy metabolism and that this alteration could be provoked by oxidative stress. The action of alpha-tocopherol and ascorbic acid on the effects produced by proline was also evaluated. For acute administration, 29- and 60-day-old rats received one subcutaneous injection of proline (18.2 micromol/g body weight) or an equivalent volume of 0.9% saline solution (control) and were sacrificed 1h later. For chronic treatment, proline was injected subcutaneously twice a day at 10h intervals from the 6(th) to the 28(th) day of age. Rats were sacrificed 12h (29(th)) or 31 days (60(th)) after the last injection. Results showed that acute administration of proline significantly diminished the activity of cytochrome c oxidase in the cerebral cortex of 29- and 60-day-old rats. On the other hand, chronic hyperprolinemia reduced this complex activity only on day 29, but not on the 60(th) day of life. In another set of experiments, 22-day-old rats or 53-day-old rats were pretreated for 1 week with daily intraperitoneal administration of alpha-tocopherol (40 mg/kg) and ascorbic acid (100mg/kg) or saline. Twelve hours after the last antioxidant injection, rats received a single injection of proline or saline and were killed 1h later. In parallel to chronic treatment, rats received a daily intraperitoneal injection of alpha-tocopherol and ascorbic acid from the 6(th) to the 28(th) day of life and were killed 12h after the last injection. Results showed that the pretreatment with alpha-tocopherol and ascorbic acid before acute proline administration or concomitant to chronic proline administration significantly prevented these effects. We also observed that proline (3.0 microM-1.0 mM) when added to the incubation medium (in vitro studies) did not alter cytochrome c oxidase activity. Data suggest that the inhibitory effect of proline on cytochrome c oxidase activity is possibly associated with oxidative stress and that this parameter may be involved in the brain dysfunction observed in hyperprolinemia.     

人抵抗素基因cDNA的克隆

目的克隆人抵抗素基因(hRETN)cDNA,为进一步研究RETN的结构和功能提供实验基础.方法应用RT-PCR方法从中国人网膜脂肪垫总RNA中扩增出RETN 基因cDNA,克隆入载体pMD18-T中,形成重组载体pMD18-T/hRETN.通过蓝白斑筛选出阳性克隆,限制性内切酶酶切鉴定后对其进行测序.结果从脂肪组织总RNA中扩增得到363 bp片段hRETN基因,其cDNA序列与Genbank hRETN基因序列基本相同.结论成功地克隆中国人hRETN cDNA.     

Macrophage response to microtextured silicone

Seven different silicone surface textures were tested for effect on macrophage spreading and metabolic activity in vitro. Variables of the textured arrays that could modify spreading were determined to be the size, spacing between, depth, density, and orientation of the individual surface events and the roughness of the surfaces. Cells were influenced by the size of the events and the roughness of the surfaces more than any other variables. Cell morphology data, surface area and perimeter, could be divided into discrete regions that correlated well with the size of the events. Cell dimensions on 5μm textures were smallest while those on smooth silicone and glass surfaces were the largest. Surface texture events may be modifying contact guidance of the cells or interacting with specific transmembrane proteins to alter cell shape and function. The mitochondrial activity of cells attached to the textured silicones was determined by measuring the amount of reduced MTT directly through live cells. Cells on polystyrene (PS), 5VP and 8VP textures were metabolically more active than cells on the other textures. PMA was used to stimulate cells on the various textures. PMA-stimulated cells, on the smaller textures, 2VP, 5VP and 5CP, were less active than test cells that were not stimulated. The inability of PMA to stimulate these cells may be due to a structural alteration of protein kinase C. An hypothesis is introduced that includes a possible mechanism of how a micrometre-sized surface texture could modify cell function.     

重组人生长激素对老年人骨盆骨折蛋白质代谢及免疫功能的影响

目的 探讨应用重组人生长激素(recombinant human growth hormone,rhGH)对接受常规肠内营养支持的老年骨盆骨折患者蛋白质代谢及免疫功能的调理作用.方法 选择多发性骨盆骨折(骨折3处以上),年龄＞70岁患者30例,随机分为2组: 治疗组15例,采用标准肠内营养 rhGH[rhGH 0.2U/(kg·d)皮下注射,共计8天];另外15例作为对照组,治疗前和治疗后的第8天,分别测定血清白蛋白、血清转铁蛋白、血清前白蛋白浓度、免疫球蛋白(IgA、IgG、IgM)、T淋巴细胞亚群(CD3、CD4、CD8),并统计医院获得性肺炎的发生情况.结果 治疗组患者在治疗后第8天的血清白蛋白、血清转铁蛋白和血清前白蛋白水平比对照组显著升高(P＜0.05), IgA、IgG、IgM、CD3、CD4、CD4/CD8与对照组相比有明显增高(P＜0.05);治疗组患者医院获得性肺炎的发生率也较对照组显著降低(P＜0.05).结论 在肠内营养支持下加用rhGH可以明显促进老年骨盆骨折患者的蛋白质合成代谢,并改善免疫功能,增加肌肉的收缩力,增强排痰力度,减少医院获得性肺炎的发生率.     

Cerebral blood flow, cerebral metabolic rate of oxygen and relative CO2 reactivity during neurolept anaesthesia in patients subjected to craniotomy for supratentorial cerebral tumours

In 10 patients subjected to craniotomy for supratentorial cerebral tumours in neurolept anaesthesia, cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) were measured twice peroperatively by a modification of the Kety & Schmidt technique, using 133Xe. The relative CO2 reactivity was assessed indirectly as the % change of the arteriovenous oxygen difference (AVDO2) per mm change in PaCO2. The patients were premedicated with diazepam 10-15 mg perorally. For induction, thiopentone 4-6 mg/kg, droperidol 0.2 mg/kg and fentanyl 5 micrograms/kg were used, and for maintenance N2O 67% and fentanyl 4 micrograms/kg/h. During the first flow measurement the median and range of CBF was 30 ml/100 g/min (range 17-45), of AVDO2 8.0 vol % (range 4.1-9.5), and of CMRO2 2.28 ml O2/100 g/min (range 1.57-2.84). During the second CBF study, AVDO2 increased to 9.3 vol % (range 3.4-11) (P less than 0.05), and CMRO2 increased to 2.51 ml O2/100 g/min (range 1.88-3.00) P less than 0.05, while CBF was unchanged. The CO2 reactivity was present in all studies, median 1.8%/mmHg (range 0.5-15.1). The correlation coefficients between jugular venous oxygen tension/saturation, respectively, and CBF were high at tensions/saturations exceeding 4.0 kPa and 55%, indicating that hyperperfusion is easily unveiled by venous samples from the jugular vein during this anaesthesia.     

青海玉树健康人甲状腺激素测定

本文对玉树(海拔3700米)正常人58例的甲状腺激素用放射免疫法进行了测定,与西宁地区和平原地区对比,结果说明玉树地区T3、T4值明显或显著低于西宁和平原地区。TSH值又明显或显著高于西宁和平原地区、西宁地区P3、T4和TSH值均明显或显著低于平原。玉树地区藏、汉之间;男、女之间也有一定差异。这可能是高原低气压,缺氧对肝脏代谢的影响,调节甲状腺激素,以求机体对高原坏境的适应。     

Free plasma magnesium following glucose loading in healthy humans

The recognized existence of a circadian pattern in extracellular magnesium balance might mirror either an inherent rhythm in the homeostasis of this ion or dietary factors. Since in vitro insulin enhances cellular magnesium uptake, the circadian rhythm in extracellular magnesium metabolism might be modulated at least in part by carbohydrate intake. To assess this hypothesis, the effects of oral glucose loading on plasma total and ionized magnesium were investigted in lean healthy humans with a negative family history for essential hypertension and diabetes mellitus. Plasma total and ionized magnesium was similar before glucose loading and 30, 60, 90, 180, and 210 min thereafter. It is therefore concluded that in healthy humans the circadian pattern of extracellular magnesium is not modulated by the metabolic and hormonal mechanisms that adjust the concentration of glucose. Received: 5 February 1997 / Accepted in revised form: 14 April 1997     

A method for calculating the mean absorption time of drugs undergoing reversible and first-pass metabolism

A method has been derived for calculating the mean absorption time of an oral drug and its interconversion metabolite which is generated from the drug systemically and presystemically. The method evolves from the convolution integral and requires plasma AUC and AUMC values after separate intravenous administration of the drug and its interconversion metabolite and oral administration of the drug. It can also be used to calculate the mean input time of a drug undergoing reversible metabolism and administered by any other extravascular route. Results of a simulation study using both errorless and errant data indicate that, when the absorption rate constant of a drug or its interconversion metabolite is not much larger than the apparent elimination rate constant, the proposed method performs satisfactorily. However, when the absorption rate constant of a drug or its interconversion metabolite is much larger than the apparent elimination rate constant, the proposed method appears to be inaccurate.