Dino Gioia

Maternal and Neonatal Plasma Cytokine Levels in Relation to Mode of Delivery

After birth, host defences must be recruited to manage the transition from an almost sterile to a normal environment. The present study was undertaken to evaluate the relationship between cytokine plasma levels and phagocyte burst in mothers and neonates during the peripartal period. Plasma levels of interleukin (IL)-1, IL-6, tumour necrosis factor (TNF)-alpha, interferon (IFN)-gamma, and granulocyte-macrophage colony-stimulating factor (GM-CSF) and whole blood superoxide anion (.O2-) generation were evaluated in 27 healthy mothers, 16 undergoing vaginal delivery (VD) and 11 elective caesarean section (ECS) and in their babies. Blood specimens were taken from the mothers at the beginning of labour, during labour, immediately after delivery and 4 days later in the VD group, and before anaesthesia, immediately after delivery and 4 days later in the ECS group; neonatal samples were taken at birth (cord blood) and 4 days later. After delivery by VD, these mothers had higher plasma levels of IL-1 beta, IL-6, IFN-gamma and higher .O2- generation than those delivered by ECS. IL-6 plasma levels and .O2- generation were higher in babies born by VD than in those born by ECS. A statistically significant correlation between IL-6 plasma levels and .O2- release was observed in cord blood of babies born by VD (r = 0.69; p < 0.006). The study demonstrates that labour plays an important role in modulating host defences in the newborn.

Hypoxia-induced free iron release in the red cells of newborn infants*

Heparinized blood samples were obtained at birth from 164 newborn infants (101 full term; 63 preterm). Intra‐erythrocyte free iron concentration and hypoxanthine plasma levels were determined by high‐pressure liquid chromatography. Intra‐erythrocyte free iron concentration was higher in preterm than in full term babies (p < 0:0001) and adults (p < 0:0001). Statistically significant correlations were observed between intra‐erythrocyte free iron concentration and hypoxanthine levels (r = 0:66; p= 0:0001), pH (r = ‐ 0:76; p = 0:0001), base excess (r = ‐ 0:79; p= 0:0001), and gestational age (r = ‐ 0:44; p= 0:0001) in both infant populations. Multiple regression analysis between intra‐erythrocyte free iron concentration in cord blood, as an independent variable, and Apgar score at 1 min, pH, base excess, hypoxanthine values, FiO2 needed for resuscitation immediately after delivery, and gestational age, as dependent variables, identified hypoxanthine levels (p= 0:0003; partial F‐test = 15.4) as the best single predictor of intra‐erythrocyte free iron concentration. In conclusion, hypoxia induces intra‐erythrocyte free iron release, and therefore enhances the risk of oxidative injury due to hydroxyl radical generation.

Superoxide Anion Release by Polymorphonuclear Leukocytes in Whole Blood of Newborns and Mothers during the Peripartal Period

ABSTRACT: Superoxide anion (·O2-) production was investigated in whole blood of mothers in the peripartal period and in neonates. Blood samples from 14 mothers undergoing vaginal delivery (VD) were tested at the beginning of labor, during labor, after delivery, and 4 d after delivery. Nine mothers undergoing elective cesarean section (ECS) were tested before anesthesia, after extraction of the fetus, and 4 d later. Seventy-two healthy, full-term newborn infants were examined at birth and on the fourth day of life. Red cell glutathione peroxidase, catalase, glutathione reductase, and superoxide dismutase activities were also measured at birth and on the fourth day of life in 26 of the 72 neonates. Higher ·O2- levels were detected in mothers undergoing VD compared with ECS (p < 0.05). A significant decrease was detected in zymosan-stimulated ·O2- production between cord and fourth-day blood samples in both VD- and ECS-delivered infants (p < 0.01). Zymosan-stimulated samples showed higher values after VD than ECS, both in cord blood (p < 0.004) and on the fourth day of life (p < 0.006). A positive correlation was found between ·O2- release in zymosan-stimulated cord blood and that found in the mothers at the beginning of labor (r 0.654; p < 0.01), during labor (r = 0.721; p = 0.008), and after delivery (r = 0.832; p = 0.0008). A positive correlation was also found between ·O2- release and glutathione peroxidase on the fourth day (r = 0.709, p = 0.014). The results of the present investigation demonstrate the role of peripartal events in modulating free radical release by polymorphonuclear leukocytes during the perinatal period.

Gender‐related differences in erythrocyte glutathione peroxidase activity in healthy subjects

objective The antioxidant property of oestrogens may partly explain the gender differences in atherosclerotic heart disease and a reduction in the incidence of coronary heart disease, as well as mortality from cardiovascular disease in women undergoing postmenopausal oestrogen therapy. In the present study, we tested the hypothesis that the antioxidant glutathione peroxidase (GSH‐Px) erythrocyte activity is gender related and is correlated with oestradiol serum levels.

Variations in erythrocyte antioxidant glutathione peroxidase activity during the menstrual cycle

Antioxidant enzymes are an important part of the defence mechanisms against free radical damage. Little is known, however, about the relationship between sex steroid hormones and cellular antioxidant systems. We have investigated the effect of physiological sex steroid changes on the erythrocyte antioxidant glutathione peroxidase (GSH‐Px) activity during the menstrual cycle in a population of healthy normomenorrhoic women.

ANTIOXIDANT ERYTHROCYTE ENZYME ACTIVITIES DURING ORAL CONTRACEPTION

Nineteen healthy young women, non-smokers and of normal weight, used a combined oral contraceptive, consisting of 20 micrograms ethinylestradiol and 150 micrograms desogestrel, for 9 cycles and were investigated before starting oral contraceptive use, and during the 3rd, 6th and 9th cycle. In all cases, the antioxidant erythrocyte enzyme activities, superoxide-dismutase (SOD), catalase (CAT) and glutathione-peroxidase (GSH-Px), were determined. Pyruvate-kinase (PK) activity was also considered as a predictable index of the age and constancy of the erythrocyte population. A steady, significant increase in GSH-Px and CAT enzyme activities was found. No significant variations were found in SOD and PK enzyme levels. These findings clearly suggest that the use of combined oral contraceptives leads to an increase in antioxidant defenses. The specific physiological and biochemical mechanisms of this response merit further investigation.

Changes in the erythrocyte antioxidant enzyme system during transdermal estradiol therapy for secondary amenorrhea

Twenty-two hypothalamic amenorrheic patients, who were non-smokers and of normal weight, received replacement therapy for 1 month with transdermal patches containing 8 mg estradiol. No other drugs were prescribed or taken during the study. Before treatment (time 0) and 1 month after its start, blood samples were taken for assay of plasma estradiol levels, the erythrocyte antioxidant enzyme activities of superoxide dismutase, catalase, glutathione peroxidase (GSH-Px), and an age-dependent erythrocyte enzyme activity, pyruvate kinase. Plasma malondialdehyde levels, as an index of lipoperoxidation products, were also detected. The results showed no significant variations in superoxide dismutase, catalase, pyruvate kinase erythrocyte enzyme activities or plasma malondialdehyde levels. A significant increase in plasma estradiol levels (time 0, 17.33 +/- 4.12 pg/ml; 1 month, 81.25 +/- 10.45 pg/ml; means +/- SD; p < 0.0001) and in GSH-Px erythrocyte activity (time 0, 11.97 +/- 2.31 IU/g hemoglobin; 1 month, 16.88 +/- 4.38 IU/g hemoglobin; p < 0.004) was found. Plasma estradiol levels correlated significantly with GSH-Px erythrocyte activity 1 month after therapy was begun (r = 0.776, p < 0.003). We suggest that estrogens restored to physiological plasma levels, stimulate erythrocyte antioxidant GSH-Px activity, improving the antioxidant power of amenorrheic patients.

Characteristics and functional properties of red cells during the first days of life

In order to evaluate postnatal red blood cell (RBC) properties and whole-blood rheology, 36 healthy full-term newborn infants were tested twice (cord blood, 4th-day blood) for whole-blood flow rate, hematocrit, hemoglobin (Hb), RBC count, mean corpuscular volume, mean corpuscular Hb and its concentration, white blood cell and platelet count, plasma fibrinogen, erythrocyte glucose-6-phosphate dehydrogenase, glutathione peroxidase (GSH-Px), glutathione reductase, catalase and superoxide dismutase. Another 38 healthy full-term newborns were tested twice for separation of erythrocytes into fractions of different density. Healthy adults were taken as control. The results showed a decreased whole-blood flow rate in blood drawn on the 4th day with respect to cord blood. A multivariate analysis with flow rate as dependent variable demonstrated a significant positive correlation with GSH-Px on the 4th day. The assays of RBC densities showed a significant increase in the first 4 days.

Erythroblast Count in Newborn Infants in Relation to Different Markers of Fetal Hypoxia 45

Aim: To investigate the relationship between absolute erythroblast count (AEC) at birth and conventional markers of fetal hypoxia in neonates with perinatal distress.

38 CYTOKINE SERUM LEVELS AND WHOLE BLOOD SUPEROXIDE ANION GENERATION IN MOTHERS AND NEWBORNS DURING PERIPARTUM

The present study was undertaken in order to evaluate the relationship between cytokine plasma levels and leucocyte burst in mothers and neonates during peripartum. Serum levels of IL-1ß, IL-6, TNF-α, IFN-γ and GM-CSF, and whole blood superoxide anion generation (SAg) were evaluated in 27 healthy mothers, 16 undergoing spontaneous delivery (SD) and 11 elective cesarean section (ECS), and in their babies. Blood specimens were taken from the mothers at the beginning of labour (BL), during labour (DL), immediately after delivery (AD) and 4 days after delivery (4DAD) in the SD group, and before the operation, AD and 4DAD in ECS group, from the cord and from the babies 4DAD. The cytokines (IU/ml) were measured by enzyme-linked immunoassay. The SAg assay was performed spectrophotometrically by the method of superoxide dismutase inhibitable reduction of ferricytochrome C, with opsonized zymosan stimulation of PMN in whole blood. Statistical analysis was performed by two-tailed “t” test and by linear correlation. After delivery, SD mothers had higher levels of IL-Iß, IL-6 and IFN-γ than ECS (IL-1ß: 55.6 ± 49 vs 38.4 ± 23 p < 0.05; IL-6: 74.8 ± 68 vs 12.8 ± 6.7, p < 0.005; IFN-γ: 1.05 ± 1.02 vs 0.55 ± 0.38 p < 0.05; mean ± SD). IL-6 was higher in SD cord than ECS (20.6 ± 13 vs 12.6 ± 2.5, p < 0.05). No differences were found between the SD and ECS groups for TNF-α and GM-CSF. SAg in mothers was significantly correlated with SAg in the cord blood of their babies (BL: r = 0.64, p <0.01; DL: r = 0.71, p< 0.001). IL-6 values in mothers BL significantly correlated with SAg in mothers AD (r = 0.62, p <0.04) and SAg in cord blood of their babies (r= 0.54; p <0.05). In conclusion, labour appears to be associated with increased IL-Iß, IL-6 and IFN-γ and more active phagocyte function.