Leptin values in placental cord blood of human newborns with normal intrauterine growth after 30-42 weeks of gestation

OBJECTIVE: To evaluate leptin values in placental cord blood of newborns with normal intrauterine growth after 30-42 weeks of gestation. DESIGN: Leptin, a protein encoded by the ob gene, plays an important role in the regulation of feeding behaviour and energy balance in rodents, primates and humans. The presence of leptin in human amniotic fluid and cord blood has recently been reported in human gestations at term and the possible role of leptin in human fetal growth suggested. However, little is known of leptin synthesis during human foetal development. Thus, the aim of our work was to measure leptin (RIA, Linco Research, Inc.) in placental cord blood of human newborns at different fetal ages. PATIENTS: One hundred and twenty-six healthy newborns with normal intrauterine growth were studied. Twenty-nine were preterm (15 males and 14 females; gestational age: 30-36 weeks) and 99 were at term (49 males and 48 females; gestational age: 37-42 weeks). RESULTS: Leptin values increase progressively throughout gestation from 1.30 +/- 0.53 ng/ml at 30 weeks of gestation to 7.98 +/- 4.96 ng/ml (mean +/- SD) at term, and correlate positively with birth weight (r = 0.56, p < 0. 005, n = 126), length (r = 0.37, p < 0.005, n = 126), BMI (r = 0.57, p < 0.005, n = 126), head circumference (r = 0.37, p < 0.005, n = 126), gestational age (r = 0.48, p < 0.005, n = 126) and placental weight (r = 0.38, p < 0.003, n = 59). Leptin values are statistically significantly lower (p < 0.005) preterm (median: 2.05 ng/ml; range: 0.7-8.3 ng/ml) than at term (median: 7.0 ng/ml; range: 1.1-28.1 ng/ml). Leptin values are also significantly (p < 0.005) higher in females (median: 7.2 ng/ml; range: 0.9-23.6 ng/ml, n = 62) than in males (median: 4.8 ng/ml; range: 0.7-28.1 ng/ml, n = 64), although there are no differences in weight (2,864 +/- 536 g in females vs. 2,937 +/- 744 g in males). Multiple regression analysis shows weight to be a positive sex-independent predictor of serum leptin values (p < 0.0005). Sex also proves to be a predictor of leptin, independently of weight and is higher in females than in males (p < 0.003). CONCLUSION: Leptin is present in placental human cord blood after 30-42 weeks of gestation. Newborn weight and sex are independent predictors of leptin values.     

Serum concentrations of calcitonin and parathormone in the cord blood of premature infants

Determinations of serum calcium (Ca), calcitonin (CT) and parathyroid hormone (PTH) were carried out in mixed cord blood of 23 preterm infants. Gestational age ranged between 25 and 37 weeks. 17 of theme were vaginally delivered while 6 were delivered by emergency Caesarean section. 4 neonates died because of respiratory distress syndrome. The serum was stored at -30 degrees C until the determinations. Serum Ca levels were determined by spectrophotometry while CT and PTH levels by RIA (Immuno Nuclear Co). In cord serum the mean (M +/- SE) Ca,CT and PTH concentrations of all neonates examined were respectively: 9,9 +/- 0,6 mg/dl; 176 +/- 44 pg/ml and 1100 +/- 446 pg/ml. Serum values of CT and PTH in preterm newborns delivered by emergency Caesarean section were significantly higher than in those neonates vaginally delivered (CT: 302 +/- 115 vs 94 +/- 9 pg/ml; p less than 0.005) (PTH:2655 +/- 1857 vs 466 +/- 59 pg/ml; p less than 0.05). No differences were observed between serum CT and PTH levels in preterm neonates of different gestational age. Both CT and PTH serum concentrations were higher in neonates who died. In conclusion, the preterm neonate is able to secrete both peptides and to maintain Ca homeostasis; the mode of delivery likely affects the CT and PTH secretion; unexplainable high CT and PTH serum levels were detected in poor outcome preterm infants.     

Changes in the tumor marker concentration in female patients with hyper-, eu-, and hypothyroidism

The levels of 6 circulating tumor markers were evaluated in a total of 131 female subjects with altered thyroid states; 36 normal subjects, 46 hyperthyroid patients with Graves' disease, and 49 primary hypothyroid patients. The mean CEA concentration was observed to be significantly higher (p less than 0.02) in hypothyroid patients than in normal and hyperthyroid patients (1.1 +/- 0.1 ng/ml, 0.8 +/- 0.1 ng/ml and 0.8 +/- 0.1 ng/ml, respectively). Similarly, the mean serum CA 125 concentration in hypothyroid patients was higher (p less than 0.02) than in normal and hyperthyroid patients (13.0 +/- 2.6 U/ml, 7.6 +/- 1.1 U/ml and 5.5 +/- 0.8 U/ml, respectively), and the mean serum CA 15-3 concentration in hypothyroid patients was significantly higher than in normal subjects (p less than 0.01) and hyperthyroid patients (p less than 0.001) (16.2 +/- 0.9 U/ml, 13.9 +/- 0.6 U/ml and 10.6 +/- 0.5 U/ml, respectively). No statistical difference was found in mean CA 19-9 in the three subject groups. AFP in the hypothyroid patients (3.6 +/- 0.3 ng/ml) was significantly higher (p less than 0.05) than in normal subjects (2.6 +/- 0.2 ng/ml) and hyperthyroid patients (1.7 +/- 0.2 ng/ml) (p less than 0.01). On the other hand, serum ferritin was low in the hypothyroid patients (65.9 8.0 ng/ml) and significantly increased (69.1 +/- 9.0 ng/ml) (p less than 0.02) with the normalization of thyroid function. In hyperthyroidism, serum ferritin (70.2 +/- 7.0 ng/ml) was significantly higher than in the hypothyroid patients (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of medium-chain triglyceride feeding or glucose infusion on glucose kinetics in the newborn rat

Hypoglycaemia which develops in starved newborn rats (0.15 +/- 0.01 mg/ml) is reversed by feeding medium-chain triglycerides (0.66 +/- 0.05 mg/ml). Despite similar glycaemia (0.71 +/- 0.07 mg/ml) starved newborns infused with glucose (10.7 mg/min/kg) show a 30% higher glucose turnover rate than medium-chain triglyceride fed animals (14.1 +/- 0.6 versus 10.6 +/- 0.3 mg/min/kg, p less than 0.01). For a comparable [6-3H]glucose turnover rate (10.5 +/- 0.3 mg/min/kg), glucose-infused (5.25 mg/min/kg) newborns have a 30% lower glycaemia (0.50 +/- 0.03 mg/ml, p less than 0.01) than medium-chain triglyceride-fed newborns. Thus, medium chain triglyceride feeding leads to a 30% decreased capacity of the tissues to utilize glucose. For a similar glucose turnover rate, medium-chain triglyceride-fed newborns have a higher blood lactate concentration than glucose-infused newborns (0.26 +/- 0.03 versus 0.15 +/- 0.02 mg/ml). However, in medium-chain triglyceride-fed newborns, the increase of blood lactate is not only due to the Cori cycle, as glucose recycling is less increased than glucose production. Thus medium-chain triglyceride increases the release of gluconeogenic precursors which are not derived from blood glucose. In presence of a glucose infusion (15.25 mg/min/kg) producing hyperglycaemia (1.35 +/- 0.05 mg/ml), endogenous glucose production is suppressed by only 37%. If 3-mercaptopicolinate, an inhibitor or gluconeogenesis, is given concomitantly, hyperglycaemia is prevented (0.72 +/- 0.08 mg/ml) and endogenous glucose production is suppressed. Glucose infusion in the hypoglycaemic newborn rat might thus lead to a precarious glucose homeostasis.     

Selenium levels in related biological samples: human placenta, maternal and umbilical cord blood, hair and nails.

A study on selenium levels has been carried out in human placenta, maternal and umbilical cord blood, hair and nails of a group of 50 mothers and in the hair of the newborns. The determinations were perfomed by electrothermal atomic absorption spectrometry. The selenium concentration obtained for each sample type was as follows: For the human placenta the values obtained were between 0.56 and 1.06 microg/g (mean +/- standard deviation: 0.81 +/- 0.02 microg/g). The levels for the umbilical cord blood were 51.1-104.2 microg/l (76.3 +/- 6.5 microg/l). For the maternal blood the values measured were between 57.3 and 117.9 microg/l (90.0 +/- 15.2 microg/l), and for hair and nails were 0.22-1.5 microg/g (0.60 +/- 0.37 microg/g) and 0.46-1.57 microg/g (0.90 +/- 0.27 microg/g), respectively. For the hair of the newborns the values obtained were between 0.40 and 2.53 microg/g (1.04 +/- 0.48 microg/g). The effect of different variables as age, habitat, nutritional index or gestation age of the mothers on the selenium concentration in the samples was studied. The influence of the habitat is significant with a confidence level of 95% for the selenium concentration in maternal blood and umbilical cord blood samples. The influence of the mothers' age is significant with a confidence level of 95% for the selenium concentration in the umbilical cord blood samples. For the placenta samples, the effect of the nutritional index is significant with a confidence level of 95%. There is a positive correlation between samples of umbilical cord blood and the newborns' hair, between placenta and umbilical cord, and between cord blood and maternal blood.     

Effects of variations in thyroid hormone serum concentrations on serum ACE-activity

Serum angiotensin converting enzyme activities were significantly increased in 26 untreated hyperthyroid patients (20.3 +/- 5.4 U/ml; P less than 0.001) compared with healthy control subjects (13.1 +/- 2.3 U/ml). In 12 patients a significant fall in enzyme activities was observed after treatment compared with pretreatment serum ACE levels (P less than 0.001). Eight patients with hypothyroidism (15.7 +/- 5.1 U/ml) and 11 athyreotic patients, totally thyroidectomized for well-differentiated thyroid cancer, showed no significant differences in serum ACE activities (14.3 +/- 2.2 U/ml) compared with control subjects. After thyroid hormone supplementation a significant increase in serum ACE activity (P less than 0.05) was found in the athyreotic patients. Addition of increasing amounts of L-thyroxine to a serum sample of an athyreotic patient showed no significant effect on ACE activity in vitro. We suggest that the elevated serum ACE activity in hyperthyroidism is not from the thyroid gland, but represents a direct effect of thyroid hormone on ACE synthesis and/or release from endothelial cells.     

Study of plasma aldosterone in normal pregnancy, in pre-eclamptic women and in cord plasma of newborns.

A radioimmunoassay without chromatography was used for the determination of plasma aldosterone in pregnancy. The mean values (+/- S.D.) of aldosterone concentration increased consistently from 23.2 +/- 5.3 ng/100 ml (n = 14) during the first trimester to 37.2 +/- 10.6 ng/100 ml (n = 17) during the second trimester and 64.0 +/- 18.8 ng/100 ml (n = 29) during the third trimester of pregnancy. The highest values were found at delivery (71.9 +/- 14.2 ng/100 ml; n = 21) and in the cord plasma of newborns (83.4 +/- 14.9 ng/100 ml; n = 21). Significantly lower plasma aldosterone values were found in the plasma of pre-eclamptic women during the third trimester of pregnancy (41.9 +/- 21.3 ng/100 ml; n = 11).     

Increase of serum somatomedin C in hyperthyroid patients with pregnancy.

In thyrotoxic women with pregnancy, serum somatomedin C (SmC) concentration was markedly elevated (mean +/- SD 13.57 +/- 4.66 U/ml) compared to thyrotoxic women without pregnancy (1.24 +/- 1.09 U/ml), non-pregnant euthyroid women previously treated for hyperthyroidism (0.87 +/- 0.30 U/ml), normal subjects with pregnancy (6.08 +/- 3.36 U/ml) and pregnant euthyroid women previously treated for hyperthyroidism (5.98 +/- 1.52 U/ml). Since SmC/growth hormone ratio was significantly more in thyrotoxic pregnant women than in normal pregnant women and euthyroid pregnant women previously treated for hyperthyroidism, and since human placental lactogen (HPL), human chorionic gonadotropin (HCG) and prolactin (PRL) do not crossreact with SmC antibody, it is suggested that excess thyroid hormone during pregnancy results in excessive hepatic somatomedin C production.     

Plasma and urinary endothelin-1 concentrations in asphyxiated newborns [corrected

The aim of this study was to determine if there is any correlation between the hypoxia induced deterioration of renal functions and urinary excretions of endothelin (ET). Therefore using a sensitive and specific radioimmunoassay, we have investigated plasma ET-1 concentrations and urine ET-1 excretions in healthy and asphyxiated newborns. Sixteen newborns (10 boys, 6 girls) with perinatal asphyxia or hypoxia of variable seriousness which were followed at Newborn Intensive Care Unit in Eskisehir Osmangazi University Faculty of Medicine were enrolled. Simultaneously, gestation and weight matched 10 newborns (6 boys, 4 girls) with no asphyxia (first minute Apgar score >7) were enrolled as controls. Plasma ET-1 concentrations of the asphyxiated infants (61.8+/-79.3 pg/ml, between 23.4-125.2 pg/ml) were higher than in the control group (29.3+/-22.1 pg/ml, between 12.3 and 50.8 pg/ml, p<0.05). However creatinine clearance values were not different between the two groups (p>0.05), mean fractional excretion of sodium levels (FeNa%) were higher in the study group than the controls (p<0.01). Urinary ET-1 concentrations in the asphyxiated infants were 144.6+/-63.4 pg/ml versus 70.1+/-27.7 pg/ml in the control group (p<0.001). The ET clearance were more elevated in the asphyxiated newborns than in the healthy infants (p<0.05). Urinary ET-1/Cr ratio in the hypoxic infants were significantly elevated in the first day of life when compared with those of healthy infants (p<0.05). Total ET excretion was negatively correlated with FeNa (%) (r=-0.603, p<0.05). Plasma ET-1 concentrations of the asphyxiated infants reduced at 48 hours of age (p<0.001). Fifth minute Apgar score was negatively correlated with urinary ET-1 levels (r=-0.615, p<0.01), urinary Na excretion (r=-0.583, p<0.01), FeNa (%) (r=-0.597, p<0.01) and total ET excretion (r=-0.560, p<0.01) and positively correlated with ET clearance (r=0.559, p<0.05). Urinary ET-1 levels were negatively correlated with umbilical artery BE levels (r=-0.612, p<0.05). To our study, elevated urinary ET-1 levels were observed during perinatal asphyxia and urinary ET-1 levels were negatively correlated with 5th minute Apgar score and cord blood base excess levels. For this reason urinary ET-1 levels could be a marker of perinatal asphyxia as cord blood ET-1 levels. With investigations showing renal production is independent from plasma and increased urinary ET-1/Cr levels in newborn with perinatal asphyxia and also negative correlation between the total ET excretion and FeNa, urinary ET-1 levels could be served as a useful marker to detecting also impaired renal functions in infants with perinatal asphyxia.     

Radioimmunoassay of testosterone in late fetal and newborn rabbit plasma, gonads and adrenal glands]

A radioimmunoassay was used for measuring testosterone in the plasma, gonads and adrenals of 28, 29, 30 and 31-day-old rabbit fetuses of both sexes and newborns. A marked sex difference was shown in the concentrations of testosterone in plasma and in gonads whereas in adrenals the levels of testosterone were low in both sexes (34 to 147 pg/10 mg). In male fetuses, plasma testosterone levels increased from the 28th (133 +/- 20 pg/ml) to the 31st day (361 +/- 119 pg/ml) of intrauterine life, reaching then the values observed in the newborns (387 +/- 73 pg/ml). Plasma from males, on the other hand contained, at all stages studied, significantly more testosterone than plasma from female fetuses (21 +/- 6 to 41 +/- 11 pg/ml) and female newborns (42 +/- 6 pg/ml). In the same way, fetal testicular testosterone concentrations varying from 1 382 +/- 218 to 2 317 +/- 333 pg/10 mg were similar to those measured in the newborns (1 940 +/- 304 pg/10 mg) and significantly higher than fetal (13 to 34 pg/10 mg) or neonatal (44 pg/10 mg) ovarian concentrations. These results showed at evidence the endocrine activity of the fetal testis during this period.     

In vivo and in vitro effect of liver on somatomedin generation

The serum concentration of circulating somatomedins was measured in the blood of healthy donors and subjects with hepatic cirrhosis, and in culture media from in vitro explants of healthy and cirrhotic human liver. Serum levels of somatomedin bioactivity were significantly lower in cirrhotic subjects (0.42 +/- 0.03 U/ml; M +/- SEM) compared with age matched controls (0.99 +/- 0.03 U/ml). Radioreceptor assay of somatomedin concentrations confirmed this reduction in cirrhotic patients (0.89 +/- 0.06 U/ml) compared with controls (1.32 +/- 0.05 U/ml). A parallel reduction in somatomedin circulating binding ability was also observed (99.43 +/- 7.28% in cirrhotic and 123.5% +/- 10.8% in normal subjects). In vitro explants from normal human liver tissue produced a significant increase (0.57 +/- 0.09 U/ml) in somatomedin bioactivity contained in the medium (0.29 +/- 0.06 U/ml), while a decreased bioactivity (0.12 +/- 0.06 U/ml) was observed with explants of cirrhotic livers. These results support a role of liver in the biosynthesis of both somatomedin and somatomedin binding protein.     

Umbilical cord ghrelin concentrations in Asian and Caucasian neonates

OBJECTIVES: To compare the relationship between cord plasma ghrelin and growth hormone (GH) concentrations and birth weight in Asian and Caucasian neonates. METHODS: We measured umbilical cord ghrelin and GH concentrations in 180 full-term newborns [4 groups of 45 according to ethnicity (Caucasian/Asian) and sex]. RESULTS: Ghrelin was detectable in all umbilical cord samples (mean +/- SD: 611 +/- 267, range 193-2,010 pg/ml). There was no significant difference in ghrelin concentrations between Asian and Caucasian male or female neonates. In contrast, GH values were significantly affected by sex (p = 0.001) and ethnicity (p = 0.006). Except for a weak (r = -0.33, p < 0.03) negative correlation between ghrelin and GH in male Caucasian neonates, ghrelin and GH concentrations were independent. CONCLUSIONS: Umbilical cord concentrations of ghrelin, a potent orexigenic and GH stimulatory agent, are similar in Caucasian and Asian newborns, suggesting that ghrelin does not play a causal role in the differences in body composition and GH metabolism observed in these neonates.     

Global DNA hypomethylation is associated with in utero exposure to cotinine and perfluorinated alkyl compounds

Environmental exposures in-utero may alter the epigenome, thus impacting chromosomal stability and gene expression. We hypothesized that in utero exposures to maternal smoking and perfluoroalkyl compounds (PFCs) are associated with global DNA hypomethylation in umbilical cord serum. Our objective was to determine if global DNA methylation could be used as a biomarker of in utero exposures to maternal smoking and PFCs. Using an ELISA-based method, global DNA methylation was quantified in umbilical cord serum from 30 newborns with high (>10 ng/ml, mean 123.8 ng/ml), low (range 1-10 ng/ml, mean 1.6 ng/ml) and very low (&lt;1 ng/ml, mean 0.06 ng/ml) cord serum cotinine levels. Y chromosome analysis was performed to rule out maternal DNA cross-contamination. Cord serum global DNA methylation showed an inverse dose response to serum cotinine levels (p&lt;0.001). Global DNA methylation levels in cord blood were the lowest among newborns with smoking mothers (mean=15.04%; 95% CI, 8.4, 21.7) when compared to babies of mothers who were second-hand smokers (21.1%; 95% CI, 16.6, 25.5) and non-smokers (mean=29.2%; 95% CI, 20.1, 38.1). Global DNA methylation was inversely correlated with serum PFOA (r= -0.72, p &lt;0.01) but not PFOS levels. Serum Y chromosome analyses did not detect maternal DNA cross-contamination. This study supports the use of global DNA methylation status as a biomarker of in utero exposure to cigarette smoke and PFCs.     

Distribution of CA 125 in placental tissues

The presence of the tumor marker CA 125 was studied in different compartments of the human placenta. Levels of CA 125 in the cytosol of chorionic villi ranged from 27-17100 U/g (median 560 U/g). In the placental amnion and chorion concentrations ranged from 175-29000 U/g, median 1060 U/g and were not statistically different. In the umbilical cord values were significantly lower (range 44-7600 U/g; median 180 U/g). Maternal serum probes were above the upper limit of normal in all cases (range 48-500 U/ml; median 131 U/ml). Immunohistochemistry detected CA 125 exclusively within the amniotic cells of the placenta and the umbilical cord. This might be because CA 125 fixes more to insoluble structures in the amnion or because of contamination of chorionic villi with the underlying decidua.     

Diagnostic utility of anti-cyclic citrullinated peptide and anti-modified citrullinated vimentin antibodies in rheumatoid arthritis

Several autoantibodies found in RA are directed to epitopes in citrullinated proteins. One of them is anti modified citrullinated vimentin (Anti-MCV). We tested the value a newly developed ELISA for the detection of antibodies against a genetically modified citrullinated vimentin (anti-MCV) in comparison with an anti-CCP based ELISA system for the diagnosis of RA. Thirty-five patients with RA (mean age; 42.6 +/- 10.87 years, mean disease duration; 9.37 +/- 3.98 years) were enrolled in this study. Twenty -five ankylosing spondylitis (mean age; 35.88 +/- 6.64 years, mean disease duration; 10.25 +/- 4.61 years), and 19 healthy subjects (mean age; 40.26 +/- 5.11 years) served as controls. Anti-CCP antibodies and Anti-MCV antibodies were measured using ELISA. In all RA patients, mean anti- CCP level was 69.07 +/- 90.43 U/ml and anti-MCV level was 665.77 +/- 1040.19 U/ml. In patients with AS, the mean anti-CCP level was 10.7 +/- 5.22 U/ml and anti-MCV level was 40.54 +/- 20.15 U/ml. In healthy controls, the mean anti-CCP level was 11.11 +/- 7.65 U/ml, anti-MCV level was 23.12 +/- 12.04 U/ml. In patients with active RA, the mean serum anti-CCP level was 100.54 +/- 98.07 U/ml and anti-MCV level was 998.74 +/- 1154.93 U/ml. In patients with inactive RA, the mean serum anti-CCP level was 8.77 +/- 1.55 U/ml and anti-MCV level was 27.59 +/- 23.10 U/ml. According to these results; In patients with RA, the mean serum anti-MCV and anti-CCP levels were significantly high compared to patients with AS and healthy controls (p=0.002, p=0.001, p=0.002, p=0.001 respectively). The mean serum anti-MCV and anti- CCP levels were significantly higher in active patients with RA than in inactive patients with RA patients (p=0.001 and p=0.001 respectively). In inactive patients with RA, the mean serum anti-MCV and anti-CCP levels were similar in patients with AS and patients (p=0.484, p=0.308, p=0.09 and p=0.222 respectively). The mean serum anti-MCV levels were correlated with DAS 28 (r=0.531, p=0.001), VAS score (r=0.332, p=0.01), ESR (r=0.458, p=0.001), serum CRP levels (r=0.568, p=0.01), serum RF levels (r=0.529, p=0.001), swollen joints number (r=0.525, p=0.001) and tender joints number (r=0.638, p=0.001). As a result; measurement of serum anti-MCV levels is useful for diagnosis of RA and combined use of anti-MCV and RF may be more useful prognostic factor than either method alone, RF and anti-CCP.     

Low levels of glucocorticoid binding sites in circulating lymphocytes of premature infants suffering from hyaline membrane disease

The number and affinity of glucocorticoid binding sites in lymphocytes of newborns and prematures were determined by a whole cell [3H]dexamethasone binding assay. The average binding capacities were as follows: 1758 +/- 245 binding sites/cell in cord blood, 2758 +/- 307 binding sites/cell in mature newborns (Kd: 6,23 X 10(-9) M), and 2031 +/- 330 binding sites/cell in prematures. No specific binding was measurable in several cases. All the prematures, who did not display a measurable glucocorticoid binding capacity, suffered from a serious hyaline membrane disease (HMD), they died on 3.5-4 days of life. HMD diagnosis was established in 12 cases in toto. The number of glucocorticoid binding sites was significantly smaller in this group (639 +/- 216 per cell) than in the case of the rest of prematures (2959 +/- 404 per cell, P less than 0.001). Our results suggest that lack of glucocorticoid receptors may be one of the causes of the HMD.     

Whole blood and serum copper levels in relation to sex and age

The copper content in whole blood and serum was determined in healthy human subjects (240 males and 217 females) by atomic absorption spectrophotometry. The mean level of copper obtained in whole blood was 104.8 +/- 20.5 micrograms/100 ml in males and 117.1 +/- 20.1 micrograms/100 ml in females. The mean level of copper in serum was 102.3 +/- 21.7 micrograms/100 ml and 123.9 +/- 30.4 micrograms/100 ml, in males and females respectively. The copper concentration in whole blood and serum in females proved to be significantly higher than in males (p less than 0.001). With respect to age, the copper level showed a slightly negative correlation which is only statistically significant in whole blood in females (p less than 0.05).     

Effect of estrogens on renal responsiveness to parathyroid hormone in elderly female subjects

The effect of estrogens on the renal responsiveness to parathyroid hormone (PTH) was examined by PTH loading tests with synthetic human-PTH (1-34) in 8 normal elderly females (mean +/- SD age, 81.0 +/- 7.1 yr) before and after administration of estrogen (Premarin 1.25 mg/day for 4 weeks). Basal urinary adenosine cyclic 3', 5'-monophosphate (cAMP) excretion showed a tendency to increase after estrogen administration (5.47 +/- 1.68 vs 6.60 +/- 2.67 nmol/100 ml GFR) and the theoretical renal phosphorous threshold showed a tendency to decrease from 3.22 +/- 0.98 to 2.73 +/- 0.56 mg/dl. The blood ionized calcium concentration did not change after estrogen administration (4.44 +/- 0.16 vs 4.32 +/- 0.20 mg/dl) and serum phosphorous (P) decreased significantly (3.65 +/- 0.47 vs 3.01 +/- 0.42 mg/dl, p less than 0.05). There was no increase in mean serum immunoreactive PTH (0.34 +/- 0.10 vs 0.34 +/- 0.05 ngeq/ml). The urinary excretions of cAMP in response to PTH loading [100 U of human-PTH (1-34), intravenously] significantly (p less than 0.05) increased (94.8 +/- 57.0 vs 196.7 +/- 118.3 nmol/100 ml GFR/h) after estrogen administration. Moreover the changes in urinary excretion of cAMP (r = 0.698, p less than 0.01) and P (r = 0.555, p less than 0.05) induced by the PTH loading were positively correlated with serum estradiol in elderly females, assessed as groups before and after estrogen administration. These results suggest that estrogens may enhance the renal responsiveness to exogenous PTH administration.     

Changes and Relationship of PAF and TNF in Rats with Myocardial Ischaemia and Reperfusion Injury

IN THIS STUDY IT IS REPORTED THAT: (1) the levels of blood platelet-activating factor and serum tumour necrosis factor significantly increased after coronary ligation and reperfusion, compared with sham-ligated controls, in an anaesthetized rat model; (2) compared with vehicle controls, pretreatment with the PAF antagonist BN 50739 (10 mg/kg, i.v.) produced significant decreases in infarct size (from 29.6 +/- 4.0% to 22.4 +/- 2.1%, p < 0.05 after 3 h ligation, and from 28.5 +/- 9.5% to 10.5 +/- 4.5%, p < 0.01 after 4 h reperfusion) and the level of serum TNF (from 10.4 +/- 7.7 U/ml to 3.9 +/- 4.8 U/ml, p < 0.05); and (3) a significan positive correlation was found between the level of blood PAF or serum TNF and infarct size. The present results indicate that PAF and TNF may be important mediators involved in myocardial ischaemia and reperfusion injury, and that PAF antagonists may exert a protective effect on ischaemic or reperfused myocardium by inhibiting the interaction of PAF and TNF.     

Global DNA hypomethylation is associated with in utero exposure to cotinine and perfluorinated alkyl compounds

Environmental exposures in utero may alter the epigenome, thus impacting chromosomal stability and gene expression. We hypothesized that in utero exposures to maternal smoking and perfluoroalkyl compounds (PFCs) are associated with global DNA hypomethylation in umbilical cord serum. Our objective was to determine if global DNA methylation could be used as a biomarker of in utero exposures to maternal smoking and PFCs. Using an ELISA-based method, global DNA methylation was quantified in umbilical cord serum from 30 newborns with high (>10 ng/ml, mean 123.8 ng/ml), low (range 1–10 ng/ml, mean 1.6 ng/ml) and very low (<1 ng/ml, mean 0.06 ng/ml) cord serum cotinine levels. Y chromosome analysis was performed to rule out maternal DNA cross-contamination. Cord serum global DNA methylation showed an inverse dose response to serum cotinine levels (p < 0.001). Global DNA methylation levels in cord blood were the lowest among newborns with smoking mothers (mean = 15.04%; 95% CI, 8.4, 21.7) when compared to babies of mothers who were second-hand smokers (21.1%; 95% CI, 16.6, 25.5) and non-smokers (mean = 29.2%; 95% CI, 20.1, 38.1). Global DNA methylation was inversely correlated with serum PFOA (r = -0.35, p = 0.06) but not PFOS levels. Serum Y chromosome analyses did not detect maternal DNA cross-contamination. This study supports the use of global DNA methylation status as a biomarker of in utero exposure to cigarette smoke and PFCs.Key words: epigenomics, umbilical cord serum, hypomethylation, cigarette smoke, perfluorooctane sulfonate, perfluorooctanoate, global DNA methylation