Changes in activity of superoxide dismutase in the human endometrium throughout the menstrual cycle and in early pregnancy

To investigate the possible role of the superoxide radical andits scavenging system in the human endometrium, the immunohistochemicaldistribution of superoxide dismutase (SOD), activities of SODand lipid peroxide concentrations were studied in the humanendometrium throughout the menstrual cycle and in early pregnancy.The endometrial epithelium showed a positive immunostainingfor Cu, Zn-SOD and Mn-SOD throughout the entire menstrual cycleand in early pregnancy. In the stroma, weak immunostaining forCu, Zn-SOD and moderate immunostaining for Mn-SOD were observedin the predecidual cells in the late secretory phase. Decidualcells in early pregnancy showed strong immunostaining for Cu,Zn-SOD and Mn-SOD. Total SOD activity in theendometrium increasedfrom early proliferative phase to mid-late proliferative phaseand further increased in the mid-secretory phase, and decreasedin the late secretory phase. The total SOD activity in the endometriumofearly pregnancy was the same level as that in the mid-secretoryphase. Cu, Zn-SOD and Mn-SOD activitieschanged in a similarmanner to total SOD activity throughout the menstrual cycleand in early pregnancy. Lipid peroxide concentration in theendometrium increased from early proliferative phase to mid-lateproliferativephase and further increased in the late secretoryphase. However, lipid peroxide concentration in theendometriumof early pregnancy was the same as that in the midsecretoryphase. These results suggested thatthe superoxide radical andits scavenging system may play an important role in the regulationof humanendometrial function.     

Lipid peroxidation and antioxidant status in human cervical carcinoma

Reactive oxygen species (ROS), represented by superoxide, hydrogen peroxide and hydroxyl radicals, have been implicated in many diseases including cancer. ROS have been known to play an important role in the initiation and promotion of multistep carcinogenesis. The cellular antioxidants play a crucial role in protection against neoplastic disease. However, very little is known about the antioxidant defense in cervical carcinoma. This is addressed in the present study. Lipid peroxides, glutathione content and the activities of antioxidant enzymes, together with vitamin C and E content, were estimated in patients who had carcinoma of the cervix, and the values were compared with those of normal women. The results showed a remarkable reduction in the content of glutathione, vitamin E and C. Activities of glutathione peroxidase and superoxide dismutase were also reduced in cervical cancer compared to normal controls (P < 0.001). This reduction was more marked in late stages (III, IV) than in early stages (I, II) (P < 0.001). Glutathione was reduced more in poorly differentiated tumors (grade III) than in well and moderately differentiated ones (grade I, II) (P < 0.05). Levels of lipid peroxides were found to be significantly higher in malignant than in normal tissue samples and their levels were correlated with advanced clinical stage (P < 0.001). Our results suggest impaired antioxidant status in carcinoma of the cervix. This impairment is related to tumor progression.     

Long-lived alphaMUPA transgenic mice show reduced SOD2 expression, enhanced apoptosis and reduced susceptibility to the carcinogen dimethylhydrazine

Calorie restriction (CR) extends the life span of various species through mechanisms that are as yet unclear. Recently, we have reported that mitochondrion-mediated apoptosis was enhanced in alphaMUPA transgenic mice that spontaneously eat less and live longer compared with their wild-type (WT) control mice. To understand the molecular mechanisms underlying the increased apoptosis, we compared alphaMUPA and WT mice for parameters associated with SOD2 (MnSOD), a mitochondrial antioxidant enzyme that converts superoxide radicals into H(2)O(2) and is also known to inhibit apoptosis. The SOD2-related parameters included the levels of SOD2 mRNA, immunoreactivity and enzymatic activity in the liver, lipid oxidation and aconitase activity in isolated liver mitochondria, and the sensitivity of the mice to paraquat, an agent that elicits oxidative stress. In addition, we compared the mice for the levels of SOD2 mRNA after treatment with bacterial lipopolysaccharides (LPS), and for the DNA binding activity of NFkappaB as a marker for the inflammatory state. We extended SOD2 determination to the colon, where we also examined the formation of pre-neoplastic aberrant crypt foci (ACF) following treatment with dimethylhydrazine (DMH), a colonic organotypic carcinogen. Overall, alphaMUPA mice showed reduced basal levels of SOD2 gene expression and activity concomitantly with reduced lipid oxidation, increased aconitase activity and enhanced paraquat sensitivity, while maintaining the capacity to produce high levels of SOD2 in response to the inflammatory stimulus. alphaMUPA mice also showed increased resistance to DMH-induced pre-neoplasia. Collectively, these data are consistent with a model, in which an optimal fine-tuning of SOD2 throughout a long-term regimen of reduced eating could contribute to longevity, at least in the alphaMUPA mice.     

冠心病患者治疗前后血清SOD、ET及T淋巴细胞亚群水平

目的:探讨了冠心病患者治疗前后血清SOD、ET及T淋巴细胞亚群水平。方法:分别应用放免法和单克隆抗体法对42例冠心病患者进行了血清SOD、ET及T淋巴细胞亚群水平检测,并与35名正常健康人作比较。结果:冠心病患者在治疗前血清ET水平显著地高于正常人组(P<0.01),而SOD和CD4/CD8比值明显地低于正常人组(P<0.01),经治疗后一个月则与正常人组比较差异无显著性(P>0.05)。结论:检测冠心病患者血清SOD、ET及T淋巴细胞亚群水平对判断病情及其预后均具有一定的临床实用价值。     

2-Mercapto-ethanol enhancement of agglutination reaction--a possible in vitro serological correlate for assessment of functional immunity in simian malaria

Conventional indirect haemagglutination test was performed in rhesus monkey sera (collected from Plasmodium knowlesi infected animals) with and without prior treatment of sera with 2-mercapto-ethanol (2-ME). Surprisingly, many sera samples showed significant enhancement of final titre with 2-ME. The 2-ME enhancement effect was more pronounced in the sera of hyperimmune monkeys on further injection of antigen or parasites. It was also noticeable in the sera during primary drug-suppressed P. knowlesi infection and appeared to have a bearing on the immune status of the animals to rechallenge. The use of a soluble antigen prepared from P. knowlesi infected erythrocytes was found to be essential in IHA test to demonstrate the 2-ME enhancement effect. Antigen prepared from freed parasites (commonly used) failed to show a similar effect in IHA. The possible role of certain T-lymphocyte products - antigen binding, non-agglutinating, 2-ME sensitive molecules - in malarial immunology has been proposed.     

丹参对缺血心肌的保护作用

目的:通过观察丹参注射液(DSZ)对缺血心肌细胞各项生化指标的影响,探讨其对心肌保护作用及其机制。方法:将小鼠随机分为四组,以40%丹参注射液0.25ml/10g灌胃处理,一周后腹腔注射垂体后叶素(Pit),复制心肌缺血模型,观察小鼠心肌组织一氧化氮合酶(NOS)及超氧化物岐化酶(SOD)活性、脂质过氧化物丙二醛(MDA)的含量、血清肌酸激酶(CK)活性。结果:DSZ预处理小鼠心肌组织NOS、SOD活性显著增加,而MDA的含量及血清CK活性显著降低(P<0.01)。结论:丹参减轻心肌缺血引发的损伤,保护心脏,其作用机制可能与增加缺血心肌组织NOS、SOD活性,减少MDA含量和血清CK活性有关。     

小儿支气管肺炎患者中性粒细胞吞噬及细胞内杀菌功能与脂质过氧化关系的探讨

目的：探讨了小儿支气管肺炎患者血液中性粒细胞吞噬及细胞内杀菌功能与脂质过氧化的关系。方法：采用普通酵母菌对62例患者及35例正常人进行中性粒细胞吞噬和细胞内杀菌功能试验和化学比色法测定血浆丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH—PX）含量，放免法测超氧化物歧化酶（SOD），并与35名正常健康人作比较。结果：小儿支气管肺炎患儿在治疗前中性粒细胞吞噬及细胞内杀菌功能均明显低于正常人（P〈0．01），S01）、GSH-PX低于正常人组（P〈0．01），而MDA显著地高于正常人组（P〈0．01），相关分析显示，中性粒细胞吞噬及细胞内杀菌功能与MDA呈显著负相关（r=-0．3118，-0．3024，P〈0．05），经10d治疗后则与正常人比较无显著性差异（P〉0．05）。结论：检测小儿支气管肺炎患儿血液中性粒细胞吞噬及细胞内杀菌功能与脂质过氧化的关系对临床诊断、治疗和预后观察有重要的临床价值。     

Influence of antibody and complement components on phagocytosis and chemiluminescence of macrophages

Macrophages are known to release reactive oxygen species (O₂^?, ¹O₂, H₂O₂, OH·) in response to various membrane stimuliHowever, our studies show that phagocytic stimulation of macrophages is not necessarily accompanied by a stimulation of the oxidative burstWhereas IgG-opsonized erythrocytes were capable to induce phagocytosis and a chemiluminescence response, both being dependent on the number of IgG bound per erythrocyte, C3b-bearing erythrocytes were well ingested but failed to induce any chemiluminescence reactionFurthermore, stimulation of macrophages, via the Fc-receptors, seems to alter their functional state in regard to the activation of a receptor, which enables them to recognize membrane lesions on the target erythrocyteThe presence of IgG and membrane lesions, e.gthe C5b-9-complex of complement, induced a marked increase in chemiluminescence compared with stimulation by IgG-bearing particles aloneThe augmented response of macrophages was at least in part due to an additional release of H₂O₂, which was not liberated in response to IgG-bearing erythrocytesThis «Alesion recognizing receptor» in the macrophage membrane could not be activated by stimulation of C3b-receptors, indicating its functional linkage to the Fc-receptors.     

Lucigenin-dependent chemiluminescence as a new assay for NAD(P)H-oxidase activity in particulate fractions of human polymorphonuclear leukocytes

The enzyme responsible for the respiratory burst in human neutrophils is an oxidase that catalyzes the reduction of oxygen to superoxide anion (O-2). Superoxide anion production may be measured by chemiluminescence (CL) in the presence of lucigenin (10,10'-dimethyl-9,9'- biacridinium dinitrate). We established an assay of the oxidase, by measuring the CL of particulate fractions of PMN in the presence of lucigenin . This CL required the addition of NAD(P)H and was very low in fractions of resting cells. In particulate fractions of PMNs stimulated with PMA selectively, the NADPH-dependent CL was found to be increased. CL was linear with protein concentrations up to 100 micrograms and was shown to be at least 10 times more sensitive for the detection of O-2 than the assay based on the spectrophotometric determination of superoxide mediated cytochrome c reduction. CL was abolished by inactivating the enzyme at 56 degrees C.     

KMG03粉针剂对大鼠实验性急性心肌缺血的保护作用

采用结扎大鼠冠脉造成急性心肌缺血模型。观察KMG03粉针剂的抗心肌缺血作用。结果：KMG03粉针剂50mg/kg和100mg/kg对大鼠实验性急性心肌缺血均有一定程度的保护作用。在改善心电图S——T段的上移、降低血清CPK,LDH方法两个剂量组均有显著作用。在缩小心肌塞范围方面,以100mg/kg组为明显,KMG03粉针剂和丹参均能保护超氧化物岐化酶活性,显著降低丙二醛含量,还能显著增加缺血心肌前列环素合成。结果表明：KMG03粉针剂对心肌缺血的保护作用与抗脂质过氧化作用有关,其促进前列环素合成作用可能与其抗心肌缺血有关。