Fat metabolism and its response to infusion of insulin and glucose in patients with advanced chronic obstructive pulmonary disease

Summary. In order to investigate fat metabolism and the regulation of lipolysis and blood fuel metabolites by insulin, nine patients with chronic obstructive pulmonary disease (COPD) with chronic hypoxaemia and seven healthy control subjects of similar age were investigated by determination of the turnover rate of free fatty acids (TOR), using 1-¹⁴C-oleic acid as a tracer, and arterial concentrations of FFA, glycerol and 3-hydroxybutyrate. The measurements were performed in the basal state and during insulin and glucose infusion, aiming at euglycaemia at insulin levels of 50 and 100 mU l^-1. The subjects' ages were 64±2.7 and 66±1.1 (mean±SEM) years in the COPD and control groups, respectively. TOR was 0.73±0.06 and 0.52±0.02 mmol min^-1 (P<0.05) in the basal state, 0.33±0.04 and 0.30±0.02 at an insulin level of 50 mU I^-1 and 0.32±0.08 and 0.24±0.02 at an insulin level of 100 mU I^-1, in the COPD and control groups, respectively. Arterial FFA concentration was 0.98±0.08 and 0.75±0.06 mmol 1^-1 (P<0.05) in the basal state in the COPD and control groups, respectively. During the clamp, the decrease in FFA mirrored that in TOR. The results show that the state of lipolysis is increased in severe COPD patients with chronic hypoxaemia. Furthermore, the results suggest a reduced effect of insulin in lipolysis.     

Carbohydrate metabolism in children receiving growth hormone for 5 years

Carbohydrate metabolism was evaluated by fasting and postprandial glucose, insulin, and hemoglobin (Hb)A_1c levels in children with chronic renal insufficiency and various other growth disorders treated with growth hormone. Mean fasting and postprandial glucose remained unchanged throughout the 5-year study period in all four study groups. Median fasting insulin levels rose from lownormal levels into the normal range after 5 years of growth hormone. Average fasting insulin level after 5 years was 10 mU/l. Median postprandial insulin values also rose, yet remained within the normal range at the 5-year mark. Mean Hb A_1c levels remained within low to middle end of the normal range in the patients with growth hormone deficiency, Turner syndrome, and idiopathic short stature. Mean Hb A_1c levels at the 5 years were slightly elevated to 6.3% for the patients with chronic renal insufficiency.     

Effect of KB-2796, a new diphenylpiperazine Ca antagonist, on voltage-dependent Ca currents and oxidative metabolism in dissociated mammalian CNS neurons

The effects of KB-2796, 1-[bis(4-fluorophenyl)methyl]-4-(2,3,4-trimethoxybenzyl)piperazine-2HCl, on the low- and high-voltage activated Ca²⁺ currents (LVA and HVA I_Ca, respectively) and on oxidative metabolism were studied in neurons freshly dissociated from rat brain. KB-2796 reduced the peak amplitude of LVA I_Ca in a concentration-dependent manner with a threshold concentration of 10⁻⁷ M when the LVA I_Ca was elicited every 30 s in the external solution with 10 mM Ca²⁺. The concentration for half-maximum inhibition (IC₅₀) was 1.9 × 10⁻⁶M. At 10⁻⁵ M or more of KB-2796, a complete suppression of the LVA I_Ca was observed in the majority of neurons tested. There was no apparent effect on the current-voltage (I-V) relationship and the current kinetics. KB-2796 delayed the reactivation and enhanced the inactivation of the Ca²⁺ channel for LVA I_Ca voltage- and time-dependently, suggesting that KB-2796 preferentially binds to the inactivated Ca²⁺ channel. KB-2796 at a concentration of3.0 × 10⁻⁶M also decreased the peak amplitude of the HVA I_Ca without shifting the I-V relationship. In addition, KB-2796 reduced the oxidative metabolism (the formation of reactive oxygen species) of the neuron in a concentration-dependent manner with a threshold concentration of3 × 10⁻⁶M. It is suggested that the inhibitory action of KB-2796 on the neuronal Ca²⁺ influx and the oxidative metabolism, in combination with a cerebral vasodilatory action, may reduce ischemic brain damage.     

2-mercaptopropionate,a novel metabolite formed during treatment with 2-mercaptopropionyl-glycine in cystinuria

Summary A new acid thiol, 2-mercaptopropionate, has been identified by GC-MS in urine from cystinuric patients on treatment with 2-mercaptopropionylglycine. The amount excreted was 50–300 µmol/24 h and it was correlated with the oral dose of 2-mercaptopropionyl-glycine. The observation may be of clinical importance as the metabolite could be a potential hazard in oxidation of fatty acids.     

糖尿病调脂药物治疗的循证医学

本文重点介绍近年来糖尿病患者调脂治疗,主要包括临床常用的他汀类、贝特类、烟酸等药物降胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白-胆固醇(LDL-C)水平、升高高密度脂蛋白-胆固醇(HDL-C),以及减少心血管事件的疗效、不良反应等。     

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.