Risto Tuimala

Findings on lipid peroxidation and antioxidant function in hypertensive complications of pregnancy

Objective To assess lipid peroxidation and antioxidant function in hypertensive complications of pregnancy.

Lipid peroxidation products, selenium-dependent glutathione peroxidase and vitamin E in normal pregnancy

Twenty healthy women with normal pregnancy were simultaneously analysed with regard to lipid peroxidation products, selenium-dependent glutathione peroxidase and vitamin E. Conjugated diene double bonds, fluorescent chromolipids and thiobarbituric acid-reactive material were analysed as breakdown products of lipid peroxidation. The level of conjugated dienes in serum rose more than 45% when pregnancy advanced from the first to second trimester, but after that it declined almost to the same level as in the first trimester. The fluorescent chromolipids tended to behave in the same way. While the lipid peroxidation products reached their highest level in the second trimester, the activity of glutathione peroxidase rose progressively till the third trimester both in erythrocytes and platelets, in spite of the stable concentration of selenium in blood and plasma. The concentration of vitamin E in serum rose progressively till the end of pregnancy, but in the relation of vitamin E to cholesterol only a slight rising tendency was noted. We suggest that in normal pregnancy lipid peroxidation is controlled by adequate antioxidative response.

The total peroxyl radical-trapping ability of plasma and cerebrospinal fluid in normal and preeclamptic parturients.

Plasma and cerebrospinal fluid total peroxyl radical-trapping antioxidative parameter (TRAP) and the main antioxidant components of TRAP (vitamin E, ascorbic acid, uric acid, protein sulfhydryl groups, and the unidentified antioxidant proportion) were analyzed in 11 preeclamptic parturients, 9 healthy parturients with an uncomplicated pregnancy, and 10 healthy nonpregnant women. In addition, the possible effects of ongoing labor were studied in 10 healthy parturients. The samples of plasma and cerebrospinal fluid (CSF) were collected at cesarean section (pregnant women) or minor surgical procedure (nonpregnant women). Normal pregnancy or ongoing labor induced no significant changes in total TRAP, as compared with nonpregnant women, but significant changes in the percentage contributions of individual antioxidants were noted in plasma and CSF. In preeclampsia, a significant increase in TRAP was noted in both plasma and CSF. This increase was mainly due to an increased proportion of uric acid and unidentified antioxidants in plasma samples, and an increased proportion of unidentified antioxidants in CSF. The concentration of CSF ascorbic acid was decreased in preeclampsia, and a negative correlation between CSF ascorbic acid and blood pressure was observed.

Proliferative Activity of Human Uterine Leiomyoma Cells as Measured by Automatic Image Analysis

Proliferative activity of uterine leiomyomas from premenopausal (n = 44) and postmenopausal (n = 12) women was investigated by automatic image analysis on frozen tissue sections using immunohistochemistry with anti-proliferating cell nuclear antigen antibody. The quantitative proliferation index (QPI) in premenopausal leiomyoma cells was significantly (p < 0.025) higher than that in leiomyomas in postmenopausal women. Leiomyomas proliferated most actively during the secretory phase. After the climacterium, leiomyomas showed no proliferative activity in the absence of hormone supply, while combined substitution with estrogen and progestagen considerably increased QPI.

Pregnancy-induced hypertension is associated with changes in maternal and umbilical blood antioxidants.

Seventeen pregnancies with pregnancy-induced hypertension (PIH) and 28 control pregnancies were analyzed with regard to maternal and fetal blood antioxidants and lipid peroxidation products (conjugated dienes). In PIH, maternal blood levels of conjugated dienes were higher than in normal pregnancy. Also the activities of platelet and plasma glutathione peroxidase (GSHPx) were higher in PIH. In umbilical cord blood, the appearance of conjugated dienes, the concentration of vitamin E and the activity of erythrocyte GSHPx were lower than the corresponding maternal values. There was no difference between PIH and normal pregnancy in the appearance of conjugated dienes in cord blood, but erythrocyte GSHPx and plasma vitamin A were lower in PIH. Cord blood plasma vitamin A showed a negative correlation to maternal mean arterial pressure. We suggest that lipid peroxidation is involved in the pathogenesis of maternal PIH, and it may also have effects on the vascular function and antioxidant status of the fetus.

Erythrocyte glutathione peroxidase activity in hypertensive complications of pregnancy.

Thirty-nine patients with hypertensive complications of pregnancy were analyzed in the third trimester with respect to erythrocyte glutathione peroxidase (GSHPx) activity. Patients with severe or superimposed preeclampsia had significantly higher activities of GSHPx than those with mild preeclampsia. We suggest that a high level of GSHPx in the severe forms of preeclampsia reflects the greatly increased peroxide load generated in this disease and is of compensatory nature, responding to the disturbed peroxide and prostaglandin metabolism.

Peripherally administered sufentanil inhibits pain perception after postpartum tubal ligation.

The clinical effectiveness of locally administered opioids is still under discussion; in particular, the potency of morphine in settings other than intra-articular arthroscopy has been questioned. We developed another pain model, postpartum resection of the fallopian tubes for sterilisation, in which each patient serves as her own control when one side is infiltrated with the active drug (in this study sufentanil 5 mg) and the contralateral side with normal saline. In the control group both sides are infiltrated with plain saline. After 30 min from the end of anaesthesia onwards, 26 out of 30 patients observed significant pain relief on the side of the sufentanil infiltration, which in 11 patients lasted until the end of the observation period 24 h postoperatively; no difference was observed in the control group. In our pain model with a high assay sensitivity, the infiltration of one side with the lipophilic test drug, sufentanil, caused local analgesia in primarily non-inflamed tissue. The use of each patient as her own control excluded inter-subject bias.

Hormonal changes during the perinatal period: Fsh, prolactin and some steroid hormones in the cord blood and peripheral serum of preterm and fullterm female infants

Fetoplacental endocrine function during the last third of gestation, and first 5 days post partum, was studied by hormone measurements of umbilical cord arterial and venous serum in preterm (31-37 weeks gestation) and fullterm (39-42 weeks gestation) female newborn. Furthermore, hormones were measured in peripheral serum of fullterm female infants of 1, 3 and 5 days of age. The data were compared with those obtained previously in corresponding age groups of males. FSH was significantly (P less than 0.05) higher in the cord serum of preterm females (5.4 +/- 1.8 IU/I, SE, n = 30) than in males (1.5 +/- 0.08 IU/l, n = 27), and decreased significantly (P less than 0.05) in preterm females towards fullterm. PRL levels increased in both sexes towards the end of gestation (P less than 0.01), and decreased post partum, but no sex differences could be detected. Testosterone was significantly higher in the male serum samples (P less than 0.01-0.05), but only minor sex differences were seen in cord serum, or post partum, concentrations of the other steroids measured, pregnenolone, progesterone, 17-hydroxyprogesterone and androstenedione. Significant arterio-venous difference (higher in the vein) were seen at term in progesterone and 17-hydroxyprogesterone. The levels of these two steroids also decreased most clearly after birth. Female serum testosterone peaked at d 1 post partum (0.084 +/- 0.014 microgram/l, SE, n = 11), decreased thereafter, but remained at the intrauterine level, suggesting that the low female levels of this steroid are of fetal, rather than placental/maternal origin. The same seems to be true for androstenedione. Our data suggest that the fetal ovary is quiescent during the last weeks of gestation.

Peripheral venous concentrations of oestrogens in postmenopausal women with ovarian cancer

Summary. Serum concentrations of oestrone, oestradiol and oestriol were measured in 23 postmenopausal women, 12 with ovarian cancer and 11 with genital prolapse. Oestrone (387.6 pmol/1) and oestradiol (72.7 pmol/1) levels were higher in the cancer group than those in the control group (159.8 and 27.5 pmol/1 respectively), while oestriol levels did not differ (434.5–270.8 pmol/1). The results indicate abnormal ovarian function in postmenopausal patients with ovarian cancer.

CYP1A1 activity in renal cell carcinoma and in adjacent normal renal tissue

Abstract Cytochrome P450-isoenzyme, CYP1A1, is responsible for the metabolic activation of several precarcinogenic environmental chemicals to their carcinogenic intermediates. Microsomal CYP1A1 activity in renal cell carcinoma (RCC) and in normal renal tissue was determined by measuring spectrofluorometrically the hydroxylation rate of benzo[a]pyrene. The study included 50 patients who underwent nephrectomy for RCC. Tissue specimens were taken from renal tumours and, as a control, from macroscopic normal renal tissue adjacent to the tumours. Normal renal tissues that were adjacent to poorly differentiated grade 3 tumours and/or to metastatic RCC contained significantly higher CYP1A1 activities than renal tissues next to well-differentiated (P = 0.02) and/or organ-confined tumours (P = 0.001). In conclusion, those patients who had tumours that could be considered aggressive on the grounds of poor cell differentiation or a metastatic feature of tumour, had remarkably higher CYP1A1 activities in their kidneys than the patients with less aggressive renal tumours.