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The authors analyzed the concentration of malonic dialdehyde (MDA) in the cerebrospinal fluid (CSF) of children with intracranial hypertension. For the control group an intracranial pressure (ICP) of 250 mm H2O was taken as a reference point. The concentration of MDA was determined by a method using thiobarbituric acid. In a group of children with ICP values greater than the limiting value, the concentration of malonic dialdehyde was 0.629 mmol/mg protein, while in the control group with an ICP below 250 mm H2O, this value was 0.610 mmol/mg protein. The differences between the two groups were not statistically significant. from the results obtained it can be concluded that the concentration of MDA, as an isolated parameter, does not constitute a good measure of intensity of the lipid peroxidation processes in central nervous system (CNS) tissues, taken as an indicator of their disintegration in cases of hydrocephalus with intracranial hypertension.

The interaction between various antioxidants may be important in protecting against oxygen toxicity. We studied the total radical trapping capacity of the antioxidants in plasma (TRAP) and compared the TRAP-level in the patients with eclampsia with that in normal pregnant women. The measured and calculated TRAP-level was higher in the control group than in the group with eclampsia. The uric acid, vitamins E and C and sulfide concentrations were lower in the group of women with eclampsia compared with the controls. The central conclusion from this work is that for patients with eclampsia, the plasma concentrations of the essential nutrients: vitamin E, vitamin C, and cysteinerich protein are too low for optimal antioxidant systems activities.

In our study of potassium levels in normal pregnant women the mean serum potassium concentration was 5.65 (0.76) (SD) mmol/l. This level decreased with maternal age and parity and increased progressively with gestational age. The value recorded in the first trimester was 4.25 mmol/l, which increased to 5.83 mmol/l in the second trimester and to 5.95 mmol/l in the third trimester. Apart from other factors that affect serum potassium levels during pregnancy, the social status of the pregnant women was also found to influence the values, rising from 4.97 mmol/l in the case of poor women to 6.03 mmol/l in the case of civil servants. The nutritional implications of this study with respect to proper fetal development is discussed.

The aim of our investigation was an attempt to determine malondialdehyde concentration (MDA) in amniotic fluid as a biochemical test in prenatal diagnosis. The investigations were carried out in 56 pregnant women and their newborns in whom IUGR was diagnosed clinically. The control group consisted of 35 pregnants who had as uneventful pregnancy and normal labour. Samples of amniotic fluid were taken in the first stage of parturition (dilatation of cervical os 4-5 cm) by vaginal amniocentesis or amniotomy during cesarean section. It was found that during pregnancy complicated by IUGR, the MDA concentration in amniotic fluid was almost three times higher than in normal pregnancy (0.785 mmol/l and 0.268 mmol/l, respectively). These differences are statistically significant at p < 0.001. Thus, determination of MDA can be used as a biochemical test in parental diagnosis of IUGR.

Amniotic fluid elastolytic activity was assessed in a group of 120 women who delivered preterm infants and in 35 women who delivered at term. Amniotic fluid elastolytic activity decreases as pregnancy progresses. The lecithin-to-sphingomyelin (L/S) ratio in women's amniotic fluid was determined by the method developed by Gluck and associates [6] and elastolytic activity by that developed by Mehdi and associates. A significant negative correlation was found between the amniotic fluid L/S ratio and amniotic fluid elastolytic activity (r = -0.932; p < 0.001). The border value of elastolytic activity that indicates lung maturity (L/S ratio equal to or greater than 2) is 2.01 +/- 0.05 mmol/min ml. In the amniotic elastolytic activity test, it is the value that differentiates mature from immature lungs. The amniotic fluid elastolytic activity test is characterized by high sensitivity (91.43%) and specificity (91.67%), high positive prognostic value (76.19%) and low negative prognostic value (2.65%). The test parameters do not therefore differ greatly from those of the Gluck test. Moreover, the amniotic fluid elastolytic activity test is cheaper and takes less time to perform.

Erythrocyte activity of glutathione peroxidase (GSH-Px) was measured in 26 patients with colon cancer and in 26 sex, age, height and weight matched controls. The patient group had a lower mean GSH-Px activity than the control group (p < 0.001). No correlation was found between glutathione peroxidase activity and sex, age, height, or weight, or between glutathione peroxidase activity and duration of the disease. The inverse correlation between the activity of this enzyme and the extent of the disease may be caused by a decreased absorption of selenium from the diseased colon. The significance of decreased GSH-Px in patients with this disease is unknown, but the possibility exists that this may further increase their risk of developing colonic cancer.

Despite similar vitamin E concentrations, erythrocytes of 25 children of smoking parents had an increased tendency (p < 0.01) to peroxidize in vitro as compared with those of 28 children of nonsmoking parents. This difference was abolished by vitamin E supplementation (100 mg alpha-tocopherol acetate/day for 14 days). The increased susceptibility to erythrocyte peroxidation in the smokers may reflect lower erythrocyte glucose-6-phosphate dehydrogenase, glutathione peroxidase and superoxide dismutase activities (p < 0.001, p < 0.005, and p < 0.02, respectively) in children of smoking parents. Children of smoking parents seem to be under sustained oxidant stress with increased plasma-conjugated dienes (p < 0.01) and dehydroascorbate (p < 0.002) concentrations. Total plasma cholesterol was similar in children of smoking and nonsmoking parents, and was unaffected by vitamin E supplementation. Indices of sustained oxidant stress in children of smoking parents were partially ameliorated by vitamin E supplementation.

The effect of a triphasic combination of ethinyl estradiol and levonorgestrel upon activities of superoxide dismutase, catalase and glutathione peroxidase in erythrocytes was compared to that of a preparation that contained ethinyl estradiol and desogestrel on the 21st day of a control cycle, of the third cycle of treatment with ethinyl estradiol/levonorgestrel or ethinyl estradiol/desogestrel (14 volunteers each), and of the third cycle of a 3-month washout period. Significant decreases were found in the activities of superoxide dismutase, catalase and glutathione peroxidase in erythrocytes with both preparations. The effect of desogestrel on the activities of the superoxide dismutase, catalase and glutathione peroxidase is similar to that of levonorgestrel. These data suggest that low-dose oral contraceptives, by decreasing the activities of antioxidant enzymes and by enhancing the lipid peroxidation, increase the risk of cardiovascular disease.

An increase in the incidence of cardiovascular disease has generally been observed in postmenopausal women. Because thromboxane A2 is both vasoconstrictor and a potent stimulus for platelet aggregation, it may be an important mediator of atherosclerosis. Its effects are antagonized by prostacyclin. We tested the hypothesis that there may be an imbalance between the release of thromboxane A2 and prostacyclin in women after menopause. We used radioimmunoassays to measure the 24-hour urinary excretion of two stable metabolites of thromboxane A2 and a metabolite of prostacyclin in 106 postmenopausal women and in 105 premenopausal women, both aged 45 to 55 years. The 24-hour excretion of 11-dehydro-thromboxane B2 (a stable metabolite of thromboxane A2) was increased in postmenopausal women whereas the 24-hour excretion of 2,3-dinor-6-keto-prostaglandin F1 alpha (a stable metabolite of prostacyclin) was decreased. Whether the imbalance in the release of these mediators is a cause or a result of atherosclerosis is unknown, but it may play a part in the development of this disorder.

The rheology of red blood cells in patients with atherosclerosis is abnormal. To investigate this further, the authors examined the effect of sera from patients with atherosclerosis on the handling of calcium by the erythrocyte membrane. Normal erythrocytes were filled with a photoprotein (aequorin) which emits light on contact with calcium. These photoprotein-loaded normal erythrocytes were then incubated overnight with the serum from normal subjects (n = 34) and from patients with atherosclerosis (n = 30). There was a significant decrease in basal calcium leakage, as measured by the amount of light produced following the addition of triton X-100. Induced calcium influx, as measured by the amount of light produced following the addition of ionophore A23817, was significantly greater in the photoprotein-loaded erythrocytes incubated overnight with the serum from patients with atherosclerosis compared with those incubated with the serum from normal subjects (p < 0.01). This modulation of Ca2+ handling in erythrocytes by a serum factor from patients with atherosclerosis could account for the alterations in erythrocyte function, such as red cell deformability, observed in atherosclerosis.

The cholesterol test was previously described and preliminary experience suggested it might be a rapid, inexpensive, and reliable indicator of fetal lung maturity. In this expanded series of 1342 patients delivered of infants within 72 hours of amniotic fluid analysis, the predictive value for mature test was 98.6%. Predictive value for immature test was 55.4%. For the phospholipid profile the predictive value was 97.0% for a mature test result, 31.2% for an immature result. These observations, coupled with its methodologic simplicity, make the cholesterol palmitate test a good first step in a cascade scheme of tests for fetal lung maturity and a valuable test in a facility where the phospholipid profile is not available 24 hours a day.

Thie biological effect of low dose radiation is little known. In the current study male Wistar rats were exposed monthly to a 60Co-source low dose whole body irradiation (0.25 Gy, per 18 months; total dose: 4.5 Gy). The glutathione disulphide (GSSH): total glutathione (GSH) ratio, the concentration of thiobarbituric acid-reactive substances and the activities of glutathione peroxidase and glutathione transferase in: small intestine, spleen, kidney, soleus muscle, and liver were analysed. Low dose irradiation is accompanied by distinct peroxidative changes in organs, observed in the small intestine, the spleen and in the kidneys. The current study suggests that the measurement of glutathione status and thiobarbituric acid-reactive substances can be proposed as sensitive parameters for low dose radiation induced changes.

Serum 18:2 (9, 11) linoleic acid concentration was measured in normal pregnancy and pre-eclampsia. The 18:2 (9, 11) linoleic acid in normal pregnancy increased progressively with advancing gestation, reaching the highest value at the end of pregnancy. The 18:2 (9, 11) linoleic acid concentration in pregnancy complicated by pre-eclampsia was significantly higher than in normal pregnancy after week 28. It is suggested that measurement of the 18:2 (9, 11) linoleic acid concentration in plasma may be useful as a predictor of the likely development of pre-eclampsia.

In patients with precancerous states and cancer of the uterine cervix prior to and after radiotherapy exhibit the decreased activity of neutrophil beta-glucuronidase. Moreover, patients treated by radiotherapy before the age 6 to 9 years demonstrate deficiency of N-acetyl-beta-glucuronidase in the above cells. The main finding in lymphocytes of the patients studied was in the appearance by diffusion of the above enzymes and of acid phosphatase in the cytoplasm, reflecting their release from lysosomes and immunological mobilization of these cells. The authors discuss the possible role of neutrophil enzymatic deficiency in lowering the antitumor cytotoxic effect of these cells.

This study investigated the influence of the location of the sampling site during enzymatic analyses of 31 human term placentae. The activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione transferase, glutathione reductase, and glucose-6-phosphate dehydrogenase were measured in fetal membranes, umbilical cords and placental disc. The disc samples were obtained from central (peri-insertion and mid-disc fetal and maternal halves), and peripheral regions. Significant variations were found. This study demonstrates the importance of defining the location of the sampling site in studies involving enzymatic analysis of the placenta.

The effect of long-term intake of hydralazine on myocardial lipid peroxidation (measured as formation of thiobarbituric acid-reactive substances and lipid peroxide concentrations), superoxide dismutase activity, and the protective action of vitamin A were studied in rats. Hydralazine was administered to rats for 6 months. Compared with the controls, the left ventricle of the hydralazine-treated animals had an increased thiobarbituric-acid reactive substance content and lipid hydroperoxide concentrations per g of wet tissue. Simultaneous administration of vitamin A prevented the changes in lipid peroxidation and significantly increased the superoxide dismutase activity compared with that in hydralazine-treated rats. The results seem to indicate that the increase of lipid peroxidation in rats treated with hydralazine is due not only to the stimulation, but also to the inhibition of superoxide dismutase activity.

Phospholipase A2 activity was significantly increased in placental homogenates from 22 patients with pre-eclampsia in comparison to placental homogenates from women with uncomplicated pregnancy. Such an abnormality may be responsible for an altered release of free arachidonic acid, thus playing a major role in the pathogenesis of this syndrome.

The metabolism of hydralazine and its pyruvic acid hydrazone was studied in a medium containing isolated adult rat hepatocytes. Hydralazine undergoes conversion to 3-methyltriazolophthalazine, while hydralazine pyruvic acid hydrazone is not metabolized in rat hepatocytes.

The collagen-like syndrome was induced in rats by hydralazine application during 5 months. Prolongation of hyperglycemia following oral glucose appeared in rats. This was accompanied by lowered levels in serum zinc, although the serum insulin levels were unchanged.

Earlier investigators have demonstrated in animal studies interrelationships between mineral elements. Serum zinc, magnesium and copper were monitored over a two year period in 120 women between the ages of 40 and 55 years. One group (65 women) was supplemented with calcium, the other served as a control. We concluded that calcium supplementation at a level of 1,500 mg Ca mainly does not affect serum zinc, magnesium and copper, however, serum copper concentration is elevated in women taking medication for hypertension.

Lymphocytes from patients with cancer of the larynx have been characterized by the activity of two enzymes involved in purine metabolism--adenosine deaminase and purine nucleoside phosphorylase. It has been shown that purine nucleoside phosphorylase activity was 1.5-fold higher in lymphocytes of patients in comparison with a group of healthy individuals. Adenosine deaminase activity in lymphocytes was elevated three to four-fold. The authors suggest that especially the estimation of adenosine deaminase activity in lymphocytes would be a useful laboratory test in the study of immune responsiveness of patients with cancer of the larynx.

In the present paper N-acetyltransferase phenotype has been evaluated in 128 patients with cancer of the larynx. Out of 128 patients, 86.7% were smokers. The corresponding control group consisted of 106 men who did not suffer from neoplastic diseases. 83.6% of the patients were slow acetylators. This is significantly different from the frequency of 60.3% of slow acetylators observed in the control group. The slow acetylators exhibited a greater susceptibility to the cancer of the larynx.

Hydralazine (1-hydrazinophthalazine) was administered in drinking water as a 0.0312% solution to randomly bred Swiss mice for life beginning at 5 weeks of age. The treatments gave rise to statistically significant incidences of lung tumors: 55% in females and 43% in males. A decreased copper concentration and superoxide dismutase activity in the lung of mice were observed. The role of copper and superoxide dismutase in the malignant process is briefly discussed.

Serum vitamin A concentrations were measured in 22 patients with laryngeal cancer and found to be significantly lower than those of patients of similar age with either nonmalignant laryngeal or other than laryngeal diseases. The levels of vitamin A in the patients with laryngeal cancer, but not in the controls, significantly correlated with serum concentrations of retinol-binding protein (RBP) and zinc. It is suggested that low levels of zinc might reduce the synthesis of RBP and thus reduce the mobilization of vitamin A from the liver stores.

LE-positive collagen-like syndrome was produced in rats with chronic hydralazine treatment. An increase in histamine level in total blood and serum was found in the hydralazine-treated animals.

The healing of myocardial infarction is accompanied by an increased accumulation of collagen in the heart muscle. Indexes of collagen metabolism (serum hydroxyproline, hydroxylysine and collagen-like protein concentration) were measured in 60 patients with myocardial infarction and 30 healthy blood donors. Determinations were carried out 1, 2, 3 days after admission and between the 10th-14th and 21st-25th day of the illness. It was found that hydroxyproline and hydroxylysine decreased in the first days of the disease, and subsequently increased in the course of the healing process accompanied by an increased collagen-like protein level. The changes did not depend on the total protein concentration.

In this study, we sought to determine the role of neutral proteases in cartilage matrix proteoglycan degradation, which occurs during the experimental hydralazine-induced collagen-like syndrome (c-l-s) in rats. The digestion of endogenous proteoglycans by neutral proteases in homogenates of cartilage from rats with c-l-s has been measured and compared with that of normal age-matched controls. Cartilage specimens from the tibial plateau were analysed for DNA and proteoglycan content, and neutral proteoglycan-degrading activity, No significant difference in cartilage DNA concentration was observed among the rats with c-l-s and the controls. Total neutral proteoglycan-degrading metallo-enzyme activity, determined by direct tissue assay, was significantly higher in c-l-s cartilage than that in control cartilage. Serine protease activity on proteoglycans was much lower than that of metalloprotease. The results of this study are consistent with the hypothesis that the neutral metalloproteases of cartilage are involved in the degradation of proteoglycans in c-l-s.

The excretion of the two hydroxylysine glycosides hydroxylysine-galactose-glucose and hydroxylysine-galactose was studied in the urine of normal healthy and experimental rats chronically treated with collagen-like syndrome inductors, hydralazine or binazine. The elevated urinary hydroxylysine-galactose-glucose and hydroxylysine-galactose strongly suggests an altered rate of collagen degradation during induced collagen-like syndrome.

The effect of a tumor-promoting skin mitogen, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on the induction of matrix degradation in the dermis of mouse skin has been examined. Dermis specimens were analyzed for proteoglycan content and neutral proteoglycan degrading activity. Total neutral metalloproteinase activity (latent plus active forms), determined by direct tissue assay, was significantly elevated in TPA-treated dermis than in control dermis. The active form of neutral metalloproteinase was significantly higher in TPA-treated dermis than in control dermis. Serine protease activity on proteoglycans was much lower than that of metalloproteinase. The increase in the total and active neutral metalloproteinase supports the hypothesis that these enzymes are involved in matrix degradation which is related to tumor promotion.

Studies of zinc and copper contents of breast milk were performed in 34 mothers during their lactation period until 5 days postpartum. They experienced no problems during pregnancy and delivery. All women had full term healthy infants, 22 were multiparous and 12 primiparous. The highest zinc concentration was found in the colostrum, and subsequently the concentration declined. Copper content was stable during the 5 days of lactation. Significantly lower zinc concentration and higher copper concentration were found in the serum of lactating women 3 days post partum, when compared with non-lactating women. Factors including lactation history, age of lactating women, serum levels of zinc and copper did not affect the contents of these trace minerals in breast milk.

Hydralazine (1-hydrazinophthalazine) was administered in drinking water as a 0.0312% solution to randomly bred female Wistar rats during 3 weeks. The average daily intake of this compound was 6.74 mg for a rat. The treatment resulted in lipid peroxidation in the nuclear fraction of the lungs. This lipid peroxidation was detected spectrophotometrically by the appearance of a peak at 233-235 nm in the spectrum of chloroform-methanol extract. The close proximity of DNA may make it a possible target for attack by free radicals.

Ionic fluoride is taken up by rabbit synovial fibroblasts in culture. The uptake was accompanied by an increased production of latent collagenase, and decreased activity of 5'-nucleotidase.

Collagen-like syndrome was induced in rats by oral hydralazine administration during 5 months. After 4 months, a subgroup of rats was shifted from the standard diet to the diet supplemented with copper (II) (60 micrograms of copper per g of pellet) as copper sulphate. A decreased serum copper concentration was noted, LE cells were observed in the blood of 75% of rats fed with standard diet. In the subgroup of copper supplemented rats, the LE cells were observed in 40% of rats only. The activity of superoxide dismutase, the antioxidative copper-dependent enzyme, was significantly lower in erythrocytes of rats fed with standard diet, than the activity in rats fed with copper supplemented diet. These results are briefly discussed.

In 38 male and 42 female healthy subjects serum concentrations of free and peptide-bound hydroxylysine were determined. There were no statistically significant differences between men and women.

Changes in skin collagen structure were studied after i.p. injection of phenylalanine mustard to rats. First order amino groups of lysine and arginine reacted with phenylalanine mustard, as stated potentiometrically. Bacterial collagenase was used to solubilize the skin collagen, and the aldehyde content of this material was measured using N-methyl benzothiazolone hydrazone. The aldehyde content was decreased in the collagen from rats skin after phenylalanine mustard injection. The observed changes in collagen may be analogous to the effect of aging, wherein collagen cross-linking is strengthened although qualitative changes in cross-linking may lower the measurable aldehydes.

The copper and zinc concentrations in 44 malignant and 48 nonmalignant women tissue samples of reproductive organs in women were measured. In malignant samples, the mean copper concentrations were 110%, 76%, and 38% higher for cervix, endometrium and ovary than the nonmalignant ones. The zinc concentrations in the analysed malignant tissues were lower than that in the corresponding nonmalignant tissues. The results of superoxide dismutase activities determinations demonstrate a considerable lowering of the enzymatic capacities to remove free oxygen radical in malignant tissues. A hypothesis for possible mechanism involving elevated copper concentrations, and decreased zinc concentrations, which may be responsible for malignant processes, are presented.

In 45 patients suffering from acquired valvular heart disease (a.v.h.d.) and in 20 controls blood serum levels of copper (Cu2+), ceruloplasmin (Clp), hydroxyproline (Hypro), hydroxylisine (Hyliz), collagen-like protein (Col-p), and daily urine excretion of Cu2+, Hypro, Hyliz and glycosamino-glicans (GAG) were determined. The comparison of the obtained mean values has shown that blood serum levels of Cu2+, Clp, Hypro, Hyliz, Col-p in the studied patients were statistically significantly higher than those found in controls, and the values of daily urine excretion of Cu2+, Hypro, Hyliz, GAG behaviour were similar. There were no significant differences between active and inactive processes and between infective and rheumatic endocarditis excluding GAG urine excretion. These elevated collagen degradation products provide evidence for disturbed collagen metabolism and confirm our previous biochemical, histopathological and ultrastructural examinations of connective tissue in patient with a.v.h.d. They also indicate that general collagenopathy might be the primary cause of a.v.h.d.

Collagen was obtained from liver tissue of rats with hydralazine-induced collagen-like syndrome. Bacterial collagenase was used to solubilize the collagen, and the aldehyde content of this material was measured using N-methyl benzothiazolone hydrazone. The aldehyde content was decreased in the in the collagen from livers of rats with collagen-like syndrome. The changes in hepatic collagen may be analogous to the effect of aging on collagen, wherein collagen cross-linking is strengthened although qualitative changes in cross-linking may lower the measurable aldehydes.

Phospholipase A2 activity was significantly increased in placental homogenates from 22 patients with preeclampsia in comparison to placental homogenates from women with uncomplicated pregnancy. Such an abnormality may be responsible for a altered release of free arachidonic acid, thus playing a major role in the pathogenesis of this syndrome.

20 healthy primigravidas were studied from 28 weeks' gestation until 4 days after delivery. In 9 of these women pre-eclampsia developed, the remaining 11 subjects who were age-matched had normal pregnancies. Plasma retinol, beta-carotene and vitamin E concentrations were measured by high performance liquid chromatography. The concentrations of retinol and vitamin E were significantly lower in the pre-eclampsia group than in the normotensive group at 28 weeks' gestation--that is before the onset of symptoms and signs of pre-eclampsia. The concentrations of retinol and vitamin E remained significantly lower in the pre-eclampsia group until delivery. It is suggested that measurement of the retinol or vitamin E concentration in plasma may be useful as a predictor of the likely development of pre-eclampsia.

Alkaline elution has been used to examine the integrity of DNA isolated from liver and kidney from rats treated with hydralazine (1-hydrazinophthalazine). Hydralazine was administered intragastrically at daily doses of 5, 10 and 25 mg per kg body weight to randomly bred female Wistar rats during 3 weeks. The relative strand scission, expressed as rad equivalents increased with increasing drug dose. The incidence of strand scission gives further support to the suggestion that hydralazine can be metabolically activated generating DNA-reactive species.