Effect of exercise on tissue anti-oxidant capacity and heart electrical properties in male and female rats

We studied the changes in the anti-oxidant capacity of tissues, such as heart, liver, and blood in male and female rats, as a parameter for evaluating oxidative stress after either a prolonged (210 min) or an exhausting bout of swimming. Furthermore, we also investigated exercise-induced changes in the electrophysiological properties, measured in vitro, of papillary muscle fibres. Small decreases of anti-oxidant capacities after prolonged exercise [0.10 (SEM 0.04) in heart, 0.43 (SEM 0.19) in liver, 0.22 (SEM 0.05) in blood] and greater decreases after exhausting exercise [0.23 (SEM 0.04) in heart, 0.90 (SEM 0.29) in liver, 0.34 (SEM 0.04) in blood] were found in tissues from the male rats. For the female rats, similar changes were found only in the blood [0.11 (SEM 0.07) and 0.35 (SEM 0.06) for prolonged and exhausting exercise, respectively]. Liver and heart anti-oxidant capacity remained unchanged after prolonged exercise, while after exhausting swimming it underwent a decrease almost the same as found in the male rats, though the swimming time to exhaustion (endurance capacity) was much greater [706 (SEM 10) min and 444 (SEM 32) min for the females and males, respectively]. The duration of the action potential, recorded from papillary muscle fibres, underwent changes related to the decreases in heart anti-oxidant capacity. In fact, the action potential duration (APD) was shorter only in preparations from the male rats after prolonged exercise, but in all preparations after exhausting exercise. After such exercise, the APD was similar for the male and female rats [37.1 (SEM 3.4) ms and 37.0 (SEM 3.6) ms, respectively]. Such a pattern was independent of stimulation frequency, since it was found substantially unchanged when the frequency was increased from 1 to 5 Hz. We concluded that the different susceptibilities to the effects of physical exercise, exhibited by tissues from these male and female rats might have been related to different capacities to oppose oxidative stress effectively.     

Astrocytes and intracerebral immune responses

The astrocyte is the most abundant cell within the central nervous system (CNS). This cell subserves a multiplicity of important functions that contribute to the process of neural development as well as to the integrity of normal brain function. Adding to the already exhaustive list of capabilities, the astrocyte has now been demonstrated to function as an intracerebral antigen presenting cell. These findings are serving to revise our view of the brain as an immunoprivileged site and perhaps will shed some light on the pathogenetic mechanisms involved in a number of CNS disorders of immune dysregulation. In this review we provide some perspective on the regulatory mechanisms that influence astrocyte immune functions. Specifically, we address the role played by the major histocompatibility complex (MHC) antigens as well as adhesion molecules in the initiation of brain immune responses.     

Transmural distribution of antioxidant defences and lipid peroxidation in the rabbit left ventricular myocardium

The left ventricular subendocardial and subepicardial layers of six perfused rabbit hearts were tested for enzymatic and non-enzymatic antioxidant defences and for lipid peroxidation. The subendocardium showed significantly lower catalase activity and contents of non-protein thiol compounds and vitamin E associated with a higher degree of lipid peroxidation. The activities of Cu,Zn- and Mn-superoxide dismutases, glutathione reductase, -glutamylcysteine synthetase and -glutamyl transpeptidase showed no significant transmural differences, and Se-independent glutathione peroxidase activity was not detectable in either layer. Comparable results were observed in another group of six unperfused rabbit hearts. In five H₂O₂-perfused rabbit hearts, lipid peroxidation was higher, and myocardial creatine phosphokinase activity lower, in the subendocarium than in the subepicardium. In this group, only the subendocardium had significantly higher lipid peroxidation levels than the control hearts. Thus, a lower antioxidant capacity and a greater oxidative stress are present in the rabbit subendocardium. These findings could provide insight into the problem of subendocardial vulnerability to free radical-mediated processes, such as occurs in ischaemia-reperfusion injury.     

牛磺酸拮抗同型半胱氨酸诱导的线粒体呼吸链自由基生成和同型半胱氨酸抑制线粒体牛磺酸转运体

目的:观察同型半胱氨酸(Hcy)对心肌线粒体电子漏及自由基生成的影响,以及观察牛磺酸的拮抗效应。方法: 分离大鼠心肌线粒体,超声波破碎线粒体制备亚线粒体,纯化制备猪心肌线粒体琥珀酸细胞色素C还原酶(SCR)重组体。分别用Hcy和/或牛磺酸共同孵育心肌线粒体、亚线粒体、SCR;用化学发光法测定H₂O₂^- 及O₂^- 生成;并用滤膜抽滤法观察线粒体膜牛磺酸转运体的性质及Hcy对牛磺酸转运功能的影响。结果: Hcy呈浓度依赖性地刺激大鼠心肌线粒体、亚线粒体氧自由基生成及SCR电子漏增加,牛磺酸自身不影响心肌线粒体、亚线粒体及SCR氧自由基生成,但呈浓度依赖性地抑制Hcy诱导的线粒体、亚线粒体及呼吸链重组体氧自由基生成。线粒体膜上存在Na+依赖性的牛磺酸转运体,Hcy呈浓度依赖性地抑制牛磺酸转运体对牛磺酸的转运功能。结论: 牛磺酸抑制Hcy刺激的线粒体呼吸链电子漏增加及氧自由基生成。线粒体膜上存在Na+依赖性的牛磺酸转运体,Hcy抑制线粒体膜上牛磺酸转运体对牛磺酸的转运功能。     

Peroxisome proliferator-activated receptor-α and liver cancer: where do we stand?

The peroxisome proliferator-activated receptor- (PPAR), first identified in 1990 as a member of the nuclear receptor superfamily, has a central role in the regulation of numerous target genes encoding proteins that modulate fatty acid transport and catabolism. PPAR is the molecular target for the widely prescribed lipid-lowering fibrate drugs and the diverse class of chemicals collectively referred to as peroxisome proliferators. The lipid-lowering function of PPAR occurs across a number of mammalian species, thus demonstrating the essential role of this nuclear receptor in lipid homeostasis. In contrast, prolonged administration of PPAR agonists causes hepatocarcinogenesis, specifically in rats and mice, indicating that PPAR also mediates this effect. There is no strong evidence that the low-affinity fibrate ligands are associated with cancer in humans, but it still remains a possibility that chronic activation with high-affinity ligands could be carcinogenic in humans. It is now established that the species difference between rodents and humans in response to peroxisome proliferators is due in part to PPAR. The cascade of molecular events leading to liver cancer in rodents involves hepatocyte proliferation and oxidative stress, but the PPAR target genes that mediate this response are unknown. This review focuses on the current understanding of the role of PPAR in hepatocarcinogenesis and identifies future research directions that should be taken to delineate the mechanisms underlying PPAR agonist-induced hepatocarcinogenesis.     

Effects of protein supplementation during prolonged exercise at moderate altitude on performance and plasma amino acid pattern

Summary The effects of two levels of protein intake on muscle performance and energy metabolism were studied in humans submitted to repeated daily sessions of prolonged exercise at moderate altitude. For this purpose, 29 healthy males, were exposed to seven successive stages of ski-mountaineering at altitudes between 2500 and 3 800 m, and to an isocaloric diet (4000 kcal·day^–1, 16760 kJ·day^–1) with either 1.5g·kg^–1·day^–1 (C group,n =14), or 2.5 g·kg^–1·day^–1 (PR group,n =15) protein intake. Measurements made after the ski-mountaineering programme did not show any change in body mass. The peak torque during maximal isometric voluntary contraction (MVC) of the quadriceps muscle was unaffected by the repeated exercises, whereas the endurance time at 50% MVC was decreased in PR subjects (–26.8%,P<0.001). Increased levels of both free fatty acids (+147%,P<0.001) and glycerol (+170%,P<0.001) observed in C subjects would suggest that lipolysis was enhanced after the repeated exercise. The plasma amino acid pattern was altered after completion of the ski-mountaineering programme; the plasma concentration of the three branched-chain amino acids (BCAA) was significantly decreased in C subjects, whereas the higher level of protein intake (PR group) greatly minimized the exercise-induced decrease in serum BCAA.     

肺动脉高压大鼠一氧化氮及过氧化氢依赖的可溶性鸟苷酸环化酶通路的变化

目的：观察低O2高CO2对血浆一氧化氮（NO）、肺组织超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、可溶性鸟苷酸环化酶(sGC)活性以及cGMP含量的变化，探讨NO-sGC和H2O2-sGC通路于肺动脉高压中的作用。 方法： 复制低O2高CO2 1、2、4周组及对照组大鼠模型。测定平均肺动脉压（mPAP）。比色法测定血浆一氧化氮（NO）、肺组织超氧化物歧化酶（SOD）、过氧化氢酶（CAT）活性，酶动力学分析基础及过氧化氢（H2O2）及硝普钠（SNP）激活的肺组织sGC酶活性，［125I］-放射免疫法检测肺组织cGMP含量。 结果： 低O2高CO2 1、2、4周组mPAP均明显高于对照组（均P<0.01）；血浆NO、肺组织SOD、CAT活性、基础sGC活性、过氧化氢（H2O2）及硝普钠（SNP）激活的sGC活性和肺组织cGMP含量均显著低于对照组（分别P<0.05, P<0.01）。 结论： 低O2高CO2抑制NO-sGC和H2O2-sGC通路参与肺动脉高压的形成与发展。     

Effect of age and ambient temperature on n-pentane production in adult housefly, Musca domestica

The objective of this study was to examine the relationship between lipid peroxidation and aging in the male housefly. Metabolic rate of flies is known to be higher and life span shorter at elevated ambient temperature. Evolution of n-pentane and level of thiobarbituric acid (TBA) reactive material were used as indicators of lipid peroxidation. n-Pentane accumulated by houseflies in vivo and by whole body homogenates of houseflies, in response to tert-butyl hydroperoxide (1 mM), increased with age. n-Pentane accumulation in vivo was markedly higher at higher ambient temperature. Furthermore, n-pentane generated by flies in vivo and by fly homogenates in vitro tended to be lower in flies raised at a lower ambient temperature. TBA-reactive material, elicited by tert-butyl hydroperoxide, was augmented in older flies, but no significant difference was found between flies aged at different ambient temperatures. Analysis of fatty acids in housefly homogenates indicated an age-associated increase in the ratio of polyunsaturated to saturated fatty acids.     

HLA antigens in affective disorders and schizophrenia

The distribution of HLA antigen frequencies has been studied in patients with affective disorders. There were no significant differences between bipolar patients, unipolar patients, or controls. Preliminary data on HLA antigen distribution in schizophrenic patients are reported. Our negative results in affective disorders are discussed in relation to HLA studies reported from other laboratories, with special reference to some potential methodological problems.     

丹参对脊髓损伤早期自由基影响的实验研究

目的通过观察大白兔脊髓损伤模型，早期及使用丹参后的变化，探讨丹参在脊髓损伤早期对自由基的作用机制。方法通过改良的Allen‘s法制作脊髓损伤模型。分别在不同时段测定血液标本和脊髓标本的丙二醛(MDA)和超氧化物歧化酶(SOD)。通过应用丹参观察上述指标的变化，并在光镜下观察组织形态的变化。结果损伤组血液标本和脊髓标本中MDA升高、SOD降低，丹参组血液标本和脊髓标本中MDA有所减低，SOD有所升高，丹参组血液标本和脊髓标本所测定的各个指标与损伤组的比较有显著性差别。组织学形态上，丹参组治疗组脊髓损伤程度小，神经元细胞破坏少。结论脊髓损伤后血液和脊髓组织中氧自由基含量升高，丹参能有效清除自由基，从而保护脊髓，在一定程度上阻止继发损伤的进一步发展。