Superoxide Dismutase Activity in Leukemic Blasts of Children with Acute Leukemia

ABSTRACT. Superoxide dismutase activity was determined in leukemic blasts of 24 patients with acute leukemia and was correlated to its type. The activity was significantly lower in five patients with T cell or B cell leukemia, and there was a wide range of distribution in IS patients with non-T, non-B cell leukemia. Manganese superoxide dismutase activity was significantly lower in all types of acute lymphoblastic leukemia than in normal mononuclear leukocytes. Both total and manganese superoxide dismutase activities in acute myeloblasts leukemia, however, were significantly higher than those in normal polymorphonuclear leukocytes. The prognosis in patients with a low superoxide dismutase activity in leukemic blasts seemed to be poorer. Determination of superoxide dismutase activity in leukemic blasts may have a prognostic value in the management of children with acute leukemia.     

Developmental patterns of antioxidant defense mechanisms in human erythrocytes

To obtain a profile of erythrocyte antioxidant defense potential during late fetal development, we studied selected antioxidant parameters in blood samples from 65 neonates with birth wt between 520 and 4210 g and from 12 healthy adults. Erythrocyte superoxide dismutase activity did not change significantly with maturation and no significant differences were observed among preterm infants grouped in increasing birth wt categories, term neonates, and adults. Erythrocyte catalase and glutathione peroxidase, as well as plasma vitamin E levels, showed highly significant positive correlations (p less than 0.001) with increasing fetal wt and gestational age; by term, CAT activity reached a level similar to the adult control group, but glutathione peroxidase activity, as well as plasma vitamin E levels, were markedly lower in all the preterm and in the term groups than in adults (p less than 0.01). Erythrocyte glutathione S-transferase activity showed a negative correlation with increasing gestational age (p less than 0.01) and the adult values were considerably lower than any of the neonatal levels (p less than 0.001). The role of glutathione S-transferase in erythrocyte metabolism remains obscure. Maturational changes in the activity of the red cell enzymes that were studied and in the plasma vitamin E level were apparent from about 31-36 wk of gestation, suggesting that the stimulation for these changes may have commenced from about 28-31 wk.     

CERULOPLASMIN LEVELS AND ERYTHROCYTE SUPEROXIDE DISMUTASE ACTIVITY IN SMALL PRETERM INFANTS DURING THE EARLY ANEMIA OF PREMATURITY

Abstract. Hågå, P. (Paediatric Research Institute, National Hospital of Norway, and Department of Paediatrics, Ullevål Hospital, Oslo, Norway). Ceruloplasmin levels and erythrocyte superoxide dismutase activity in small preterm infants during the early anemia of prematurity. Acta Paediatr Scand, 70: 861, 1981.-Ceruloplasmin plasma levels and erythrocyte superoxide dismutase activity were studied in appropriate for gestational age preterm infants (birth weights ≤1500 g) during the first 10 weeks of life. Preterm infants had significantly lower ceruloplasmin concentrations in cord blood than term infants, the mean level in the preterm infants being 0.07 g/I. At 1 week of age ceruloplasmin levels had risen significantly, whereupon a fall occurred at 2 weeks of age. Ceruloplasmin concentrations increased slowly and progressively from 4 weeks of age. The low ceruloplasmin concentration during the early anemia of prematurity seems not to interfere with iron mobilization. The superoxide dismutase activity per gram hemoglobin in cord blood erythrocytes from normal term infants was significantly lower than that of red blood cells from adults. When the activity was expressed per erythrocyte no difference was found. The normochromic macrocytic red blood cells of the neonate most likely explain this discrepancy. The erythrocyte superoxide dismutase activity of the preterm infants did not change from birth until 10 weeks of age, and the levels seemed adequate judged from the levels found in red blood cells from adults and cord blood from term infants. Neither ceruloplasmin nor erythrocyte superoxide dismutase activity seem to play a role in the etiology of the early anemia of prematurity.     

Erythrocyte Cu/Zn superoxide dismutase activity in preterm infants with and without bronchopulmonary dysplasia

BACKGROUND: Erythrocyte Cu/Zn superoxide dismutase is believed to play a major role as a first-line antioxidant defense. Studies have reported varying results from measures of superoxide dismutase activity in cord blood samples from neonates. OBJECTIVE: The study goal was to assess enzyme activity for preterm infants representing a range of gestational ages during the 1st week of life. Clinical data were obtained and correlations with superoxide dismutase activity were examined. METHODS: We collected blood samples from umbilical arterial lines or the radial artery of 44 preterm infants (gestational age range 25-30 weeks) on days 1, 3, and 6 after delivery and evaluated erythrocyte Cu/Zn superoxide dismutase activity. RESULTS: There was no correlation between enzyme activity and gestational age or birth weight. Superoxide dismutase activity gradually increased in preterm infants with bronchopulmonary dysplasia on days 3 and 6, with levels significantly higher than those of preterm infants without bronchopulmonary dysplasia on day 6. We found that packed red cell transfusion did not affect erythrocyte superoxide dismutase activity in either group. However, higher cumulative oxygen administration was noted in preterm infants with bronchopulmonary dysplasia. CONCLUSION: Higher cumulative oxygen administration may be one factor that upregulates the activity of erythrocyte superoxide dismutase.     

Nitrofen-induced diaphragmatic hernias in rats: pulmonary antioxidant enzyme activities.

We developed an experimental rat model of congenital diaphragmatic hernia (CDH) to elucidate the etiology and pathogenesis of this serious congenital anomaly in humans and in particular to study the effects of a short period of artificial ventilation on the CDH lung in relation to antioxidant defense mechanisms. CDH was induced in about 60% of the offspring by maternal exposure to 2,4-dichlorophenyl-p-nitrophenylether (Nitrofen) during pregnancy. This herbicide resembles thyroid hormone in chemical structure. The lungs of fetal rats (d 19, 20, 21, and 22) were examined for protein and DNA content and activity of superoxide dismutase, catalase, and glutathione peroxidase (GPX). The same parameters were assessed in tracheotomized newborn rats after pressure-controlled artificial ventilation with either room air or pure oxygen during a short period of 5 h. In both CDH rats and controls, wet lung weight increased during gestation. At term, CDH rats had significantly lower mean lung weights than controls. Neither group differed in protein and DNA content per mg lung or superoxide dismutase, catalase, and GPX activity before and at birth. After artificial ventilation of neonates with air and pure oxygen, superoxide dismutase activity tended to decrease, whereas catalase activity remained virtually unchanged in the CDH lung. However, GPX activity in the CDH lung was reduced to 80% of initial activity at term after ventilation with air and to 70% with pure oxygen. The present finding of a decline in GPX activity in this animal model after a short period of artificial ventilation may indicate that the CDH rat neonate is at risk to develop oxygen-related lung damage.     

Pulmonary antioxidant enzyme maturation in the fetal and neonatal rat. I. Developmental profiles

Neonatal, adult, and fetal rat lungs of 18, 20, and 22 d gestation from four to six litters were examined for cytochrome oxidase, glucose-6-phosphate dehydrogenase, catalase, glutathione peroxidase, copper-zinc and manganese superoxide dismutase activities. All results were corrected for the contribution of enzymes in blood that contaminate homogenates. Because lung protein/DNA ratios and body water change significantly with gestational age, enzyme activities were expressed as U/mg DNA. All activities were low in d 18 lung and increased with advancing gestational age. Only catalase and copper-zinc superoxide dismutase increased activity in response to air breathing, suggesting that maturation of the antioxidant enzyme system is virtually complete before delivery. Activities of glucose-6-phosphate dehydrogenase, catalase, glutathione peroxidase, and manganese superoxide dismutase were higher in neonatal than in adult lung.     

Superoxide dismutase activity and lipid peroxidation of the rat liver during development

The present work was an attempt to understand the effects of oxygen toxicity in the early neonatal period and was performed using rat liver homogenate and mitochondria as examples of superoxide dismutase (SOD) activity and lipid peroxidation. SOD activity of the liver was extremely low during the fetal period and approximately the 5th day after birth. However, a rapid increase in the level of activity was observed from about the 10th day after birth. By the 20th day, this had reached 88% of the level in the adult rat. Peroxidated lipids, in an inverse relation to SOD activity, occurred at high levels during the fetal and early neonatal period, but rapidly decreased after the 10th day. It can be considered, therefore, that protection against oxygen toxicity is inadequate in such rat livers during the fetal and early neonatal periods, but that it is well established by the 10th day after birth.     

Circulating concentrations of chemokines in cord blood, neonates, and adults

Chemokines are critical for the movement of leukocytes. Chemotaxis is deficient in neonates, particularly those delivered prematurely, and this likely contributes to their increased vulnerability to sepsis. The concentrations of circulating chemokines in neonates have not been reported, nor is it known whether low chemokine concentrations contribute to their defective chemotaxis. We hypothesized that serum concentrations of chemokines 1) would be lower in preterm than term neonates, and 2) would be lower in preterm and term neonates than adults. Samples were obtained from preterm and term neonates with normal neutrophil and eosinophil counts, umbilical cord blood samples from pregnancies without clinical evidence of intra-amniotic infection, and healthy adult volunteers. The concentrations of epithelial neutrophil activating peptide-78, growth-related oncogene-alpha, eotaxin, RANTES (regulated upon activation, normal T cell expressed and secreted), and macrophage inflammatory protein-1 alpha were measured using specific ELISA. Serum concentrations from preterm infants were either similar to or higher than those measured in term neonates and adults. We conclude that the chemotactic defect observed in premature neonates is not the result of diminished circulating concentrations of any of the specific chemokines we measured.     

Postnatal development of enzyme activities associated with protection against oxidative stress in the mouse

A number of enzyme systems are important in the protection of cells from chemical-induced oxidative damage. Little is known of the relative importance of these enzymes during postnatal development and its is possible that changes in their activity during this period may alter the susceptibility to toxic agents. This study investigated the activities of glutathione peroxidase, glutathione reductase, catalase, superoxide dismutase, gamma-glutamyl-cysteine synthetase and glutathione synthetase in the liver, lung and kidney of postnatal and adult mice. The first 3 postnatal weeks are characterized by marked changes in the activities of enzymes that protect against oxidative stress (glutathione peroxidase/reductase, catalase and superoxide dismutase). Overall, the activity of these enzymes suggests that the mouse has a higher level of protection against peroxides at various stages during this period but lower capacity to detoxify superoxide anions. The activities of the glutathione-synthetic enzymes (gamma-glutamylcysteine synthetase and glutathione synthetase) were significantly lower in the kidney of the postnatal mice, but the liver and lung had levels similar to those in the adult. Glutathione turnover in the liver of 2-week-old mice was not different from that in adults. The results indicate a complex pattern of development in the activities of detoxification enzyme systems during postnatal development.     

Erythrocyte cupric/zinc superoxide dismutase exhibits reduced activity in preterm and low-birthweight infants at birth

In a comparative study in term, preterm and low-birthweight infants, the mean activity and standard error of the mean for copper/zinc superoxide dismutase (Cu/Zn SOD) in cord erythrocytes from five term small for gestational age infants was 0.94 ±0.10 SOD units (mg protein)⁻¹. This value was significantly lower than the activity (2.34 ± 0.24) in nine term, appropriate for gestational age (AGA) babies ( p < 0.005). In 15 preterm (AGA) infants, the activity at birth (1.05±0.07SOD units (mg protein)⁻) was also significantly lower ( p < 0.001) relative to term AGA babies. An increased level of activity (1.59 ± 0.09) was detected in the red cells of eight preterm AGA infants on their expected date of delivery compared with (0.87 ± 0.06) at birth ( p < 0.001). However, the activity (1.59 ± 0.09) was still lower than that detected in term AGA babies (2.34 ±0.24; p < 0.02). Similar findings were obtained when enzymatic activity was expressed in units per millilitre of packed erythrocytes. The low activity of Cu/Zn SOD in preterm and low-birthweight babies may render them susceptible to diseases associated with membrane lipid peroxidation.     

Expression of gamma-glutamylcysteine synthetase during development

Prematurity has been associated with low glutathione (GSH) concentrations in bronchoalveolar lavage fluid as well as in leukocytes from tracheal aspirates and peripheral blood. To elucidate whether this is caused by deficient GSH synthesis, the expression and activity of gamma-glutamylcysteine synthetase (glutamate-cysteine ligase, GCS, EC 6.3.2.2), the rate-limiting enzyme for GSH synthesis, were measured from fetal, neonatal, and adult human liver, lung, and kidney samples. The highest activity was measured in the liver, in which mRNA expression of the catalytic GCS heavy and the regulatory light subunits, as well as activity, were, on average, similar in the various stages of development. Although GCS light subunit mRNA concentrations in the lung were higher in neonates than in fetuses and adults, enzyme activities were similar. In the adult kidney, mean enzyme activity was somewhat higher than in fetal or neonatal kidney, but this may be accounted for by the variation in the small number of samples. In conclusion, GCS is expressed and active already in the second trimester and thus low GSH concentrations found in preterm neonates appear not to be explained by deficient GSH synthesis. Other factors, such as limited availability of the GSH precursor cysteine or increased GSH consumption, may account for the lower concentrations of GSH found in preterm infants.     

Study of the sensitivity of neonates to digoxin: contribution of erythrocyte 86rubidium uptake test

In general, there is little agreement how digoxin should be used in newborn, and the results of studies in this field seem contradictory. This study attempts a quantitative assessment of the number and the sensitivity of cellular receptors for digoxin in the organism, by the in vitro measurement of erythrocyte 86Rubidium uptake in neonates compared with adults and old people. Red blood cells are first incubated with differing concentrations of digoxin, and then incubated with 86Rb. The initial level of 86Rb uptake (Rbi) is that observed in the absence of digoxin. The 50% index of captation (IC50) is the digoxin concentration in nanograms per ml at which 86Rb uptake is half Rbi. Three groups of patients were studied: Group I: 12 neonates, less than 5 days old; Group II: 11 adults (26 to 57 years old); Group III: 9 elderly people (71 to 82 years old). Rbi was significantly lower in neonates (Mean +/- SD: 25.8% +/- 3.5, P less than 0.001) and in the elderly (29.9% +/- 3.1) than in adults (36.8% +/- 4.6). IC50 was significantly lower in the elderly (12.1 ng/ml +/- 2.4) than in the adult patients (20.5 ng/ml +/- 5.5, P less than 0.001). In the newborns, values of IC50 were widely scattered (16.2 ng/ml +/- 7.2). The authors suggest that since Rbi reflects Na+, K+-ATPase activity, this activity is diminished in newborn and old people, and indicates that they have fewer cellular receptors for digoxin than adults. In the elderly, the low IC50 would imply increased sensitivity to digoxin. In neonates, the wide range of values for IC50 suggests considerable individual variation in sensitivity to digoxin. The results are consistent with the recently recommended lower dosages of digoxin in neonates.     

新生儿中性粒细胞CDllb表达的研究

目的 在分子水平上了解新生儿中性粒细胞的功能状态。方法 采用全血流式细胞术和直接免疫荧光法检测了33例正常足月新生儿中性粒细胞CD11b平均荧光强度（MFI）。10例健康成人作对照。结果 自然分娩脐血和成人静脉血中性粒细胞CD11b MFI均低于择期剖宫产脐血和新生儿静脉血（P均＜0．05），自然分娩脐血和成人静脉血间CD11b MFI差异无显著性（P＞0．05）。结论 分娩方式影响新生儿中性粒细胞CD11b表达。足月儿中性粒细胞静息状态下CD11b表达已基本成熟。     

Cord gamma glutamyl transpeptidase activity and neonatal jaundice.

gamma Glutamyl transpeptidase (GGT) activity was measured in normal neonates and in maternal serum post partum. Levels were above the normal adult range (35I U/1) in all neonates and a significant correlation was bound between enzyme activity and bilirubin levels on day 7(P less than 0-005). The mean bilirubin level on days 4 and 7 was higher in babies with cord values less than 90 IU/1. In certain circumstances increased plasma GGT activity may serve as an index of enzyme induction. However, our results suggest that raised levels in the neonate may reflect hepatic microsomal damage with subsequent impairment of bilirubin conjugation. Further evaluative studies of cord GGT activity in neonates at risk, with a view to early prophylactic or therapeutic measures, are indicated.     

The effect of hyperoxic exposure on antioxidant enzyme activities of alveolar type II cells in neonatal and adult rats.

Neonatal animals of several species are more tolerant of hyperoxic exposure than are adults, but the mechanisms of increased neonatal tolerance are unknown, as are the cell types, if any, that contribute to oxygen resistance. We studied the effect of in vivo exposure to 85% oxygen for 72 h on the activities of the antioxidant enzymes, glutathione peroxidase, catalase and superoxide dismutase (SOD), in alveolar type II cells and whole lung from adult and neonatal rats. Baseline antioxidant enzyme activities were generally lower in neonatal type II cells compared with adults. Baseline enzyme activities did not differ in neonatal type II cells and lung homogenates except for lower catalase activity in type II cells. Hyperoxic exposure resulted in 35-38% increases in antioxidant enzyme activities in neonatal whole lung. In neonatal type II cells, SOD activity increased by 170% after hyperoxia, whereas catalase and glutathione peroxidase were not significantly changed. In the adult whole lung, hyperoxic exposure resulted in increases in only glutathione peroxidase activity, whereas in adult type II cells there was a significant decrease in SOD activity after O2 exposure. Therefore, although baseline antioxidant enzyme activities were not higher in neonatal type II cells compared with whole lung, there were differences in the antioxidant enzyme responses of adult and neonatal type II cells to hyperoxia, particularly with respect to SOD. The ability of the neonatal type II cell to respond to hyperoxia with an early increase in SOD activity may contribute to the enhanced oxygen tolerance of the neonate.     

Anti-oxidant enzymes and related elements in term and preterm newborns

Background:  Although oxidative stress-related diseases mostly affect neonates with extremely low birthweight, healthy preterm newborns might also be at risk of oxidative damages. The aim of the present study was to verify this possibility.
Methods:  Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), erythrocyte glutathione peroxidase (GSHPx) and superoxide dismutase (SOD), plasma and erythrocyte concentrations of selenium, zinc and copper were measured until 100 days of life in 30 preterm infants with mean ± SD birthweight and gestational age of 1605 ± 122 g and 34.5 ± 0.5 weeks. The control group included 30 term infants with birthweight 3123 158 g and gestational age 39.6 0.7 weeks.
Results:  Throughout the study period urinary 8-OHdG, taken as a marker of oxidative stress, was significantly higher in the preterm than in the term group. Up until 20 days of life, GSHPx activity was significantly lower in the preterm than in the term infants but this was not associated with any apparent selenium deficiency. Conversely, up until 100 days, preterm infants had significantly reduced SOD levels that appeared to reflect a shortage of the elements needed for this enzyme's activity, notably copper, the plasma concentrations of which were constantly and significantly below the control values.
Conclusion:  The nutritional status of the elements related to the anti-oxidant enzymes, especially zinc and copper, should be carefully assessed in preterm infants, even if their birthweight is not extremely low.     

Neutrophil functions of Chinese neonates

OBJECTIVE: To delineate neutrophil function of preterm and full-term neonates of Chinese origin. METHODS: Chinese neonates admitted to two major Hong Kong neonatal units were randomly selected for the study. Candidacidal activity, phagocytosis, chemotaxis and nitroblue tetrazolium reduction scores were evaluated from blood. RESULTS: Except for chemotactic activity, the neutrophil functions of Chinese preterm neonates were similar to Chinese full-term neonates. The candidacidal activity of males was significantly lower when compared with female neonates. Compared with adult controls, both term and preterm infants had similar phagocytic activities although their candidacidal activities and chemotactic index were significantly decreased. Neutrophil function of Chinese infants was nearer to that of adult controls than historically reported for western infants. CONCLUSION:: Preterm Chinese neonates had similar neutrophil function to full-term infants. Neutrophil function of Chinese infants was more mature than that of western infants.     

不同压力高压氧治疗对新生儿HIE疗效观察

目的：研究发现高压氧(HBO)可以降低新生儿缺氧缺血性脑病（HIE）的伤残率和病死率,因而用于HIE的治疗,但临床报道所使用的治疗压力及疗效各不相同。该文通过观察HBO治疗前后机体氧化、抗氧化水平变化,脑血管舒缩调节因子和神经行为评分（NBNA）的变化,探讨不同压力HBO治疗对HIE的疗效。方法：随机将收治的60例HIE患儿按所使用的治疗压即绝对压（ATA）的不同分别分1.4 ATA,1.5 ATA,1.6 ATA三组,采用不同压力HBO治疗,每天1次,7 d为一疗程。各组均在HBO第一次治疗前和最后一次治疗后,测血清MDA,SOD,NO,NOS,查NBNA和眼底。结果：3组不同压力HBO治疗前后患儿血清MDA,SOD,NO,NOS比较, 差异有显著性意义(P<0.01);1.4 ATA和1.6 ATA 高压氧治疗后患儿血清MDA,SOD,NO,NOS比较, 差异有显著性(P<0.05)。3组治疗前后患儿NBNA比较, 差异有显著性意义(P<0.05)。3组不同压力HBO治疗前后患儿眼底检查无异常。结论：1.4 ATA,1.5 ATA,1.6 ATA 3组压力HBO综合治疗新生儿缺氧缺血性脑病过程中,随着压力的增高机体抗氧能力逐渐增强,至1.6 ATA时MDA均值最低,SOD均值最高。NO,NOS含量较治疗前下降。3组压力的HBO综合治疗HIE均安全、有效。     

Altered anti-oxidant status and increased lipid peroxidation in marasmic children

BACKGROUND: Protein energy malnutrition (PEM) is a common pediatric health problem in developing countries. Although the clinical features of PEM are well known, its pathophysiology is still unclear. Free radicals have been implicated in pathogenesis of PEM. In the present study, oxidant/anti-oxidant status in marasmus was investigated. METHODS: Red cell glutathione, glutathione peroxidase and superoxide dismutase and their related cofactors, serum selenium and copper, were studied in marasmic and control children. Serum lipid peroxidation was also evaluated to assess oxidative stress. RESULTS: The red cell glutathione levels and glutathione peroxidase activities were found to be significantly lower in the marasmic children than in the controls. Red cell superoxide dismutase (SOD) activity was not different between two groups. Serum selenium and copper concentrations were significantly lower in the marasmic children than in the control subjects. The malondialdehyde concentration, which is an index of lipid peroxidation, was significantly higher in the marasmic group compared with the controls. CONCLUSION: The anti-oxidant defense system was affected in marasmic children. Reduced anti-oxidant status and increased oxidative stress occurs in marasmic children.