Concentration of metals, ceruloplasmin, metallothionein and the activity of N-acetyl-beta-D-glucosaminidase and gamma-glutamyltransferase in pregnant women who smoke and in those environmentally exposed to tobacco smoke and in their infants. Part I

Concentrations of metals (Zn, Cu, Se, Cd), metallotionein (MT) and ceruloplasmin (Cp), and the activity of N-acetyl-beta-D-glucosaminidase (NAG) and gamma-glutamyltransferase (gammaGT) in pregnant women who smoke and in passive smokers as well as in their newborns were measured. In smoking women a many-fold increase in cotinine concentrations in maternal and infant urine, amniotic fluid, placenta and milk was found as compared to passive smokers. Smoking lowered serum Se concentration in mothers and infants, increased serum ceruloplasmin in mothers and decreased serum Cu concentration in infants. Serum Zn level in infants was higher than in mothers, and smoking furthered its increase. Statistically significant increase in concentrations of Cd in placenta, amniotic fluid and milk, of Cu in placentae and amniotic fluid and of Zn in placenta and milk was revealed. Higher concentrations of metals were accompanied by an elevated MT level in placenta and amniotic fluid. In smoking women a significant increase in NAG activity in urine, amniotic fluid and milk, increase in gammaGT activity in urine and amniotic fluid and decrease in gammaGT activity in milk and placenta were observed. There was high, positive correlation between MT/NAG and MT/gammaGT in amniotic fluid of passive and active smokers, while similar correlation in milk was indicated only in the group of active smokers. The biochemical parameters analysed proved their usefulness in the evaluation of effects of exposure to cigarette smoke on pregnant woman and her fetus.     

Placental copper transport in rats: effects of elevated dietary zinc on fetal copper, iron and metallothionein

We hypothesized that the competition between zinc (Zn) and copper (Cu) during fetal accretion of copper could be discriminated at either the dam-to-placenta or placenta-to-fetus stage. This premise was tested by feeding dams a high Zn diet (1000 mg/kg, HZn) during the second half of gestation. One day before delivery, dams were anesthetized, fetuses removed and both maternal and fetal tissues and plasma obtained and assayed. Other rats were fed a normal Zn concentration diet (32.4 mg/kg, ND) throughout pregnancy. There were significantly lower fetal liver Cu concentrations and greater plasma Fe concentrations, but not plasma Cu concentrations or liver Fe concentrations in the HZn group. Both dam and fetal Zn liver concentrations were greater in the HZn than in the ND group. Plasma Cu levels were lower in the HZn-fed than in the ND-fed dams. Placental tissue from the HZn litters had a greater concentration of Zn and Fe than did the ND group, whereas no effect was noted for Cu concentration. Metallothionein (MT) levels were elevated in dam livers and placenta in the HZn group, but there were no differences in fetal liver MT. The dynamic assessment of placental transport was conducted by injecting 2.5 mg/kg Cu acetate intravenously into dams of both groups. Sequential samplings of dam and fetal blood and placentas were taken from 0 to 60 min. After the Cu bolus, there was a consistently higher plasma Cu concentration in the HZn than in the ND dams, but no alteration in the concentration of Cu in the placenta or fetal plasma. This study indicates that placental Cu uptake is not affected by a high Zn diet in the dam. In addition, the greater Zn concentration in the placenta of HZn than in ND litters results in abnormal fetal Cu, Fe and Zn concentrations, suggesting that an imbalanced maternal mineral consumption is deleterious to normal divalent metal accretion.     

Efficacy of amphipathic dithiocarbamates in intracellular cadmium mobilization and in modulation of hepatic and renal metallothionein in cadmium pre-exposed rat

Forty-eight hours after an intraperitoneal injection of cadmium chloride (1.5 mg Cd/kg) to female albino rats, Cd was mainly localized in the hepatic and renal supernatant cytosolic fraction (SCF). Seventy-two hours later, the total hepatic burden remained unchanged but the total renal burden was enhanced, showing its tendency to accumulate in the kidney. A single dose (0.4 mmol/kg, i.p.) of sodium N-benzyl-D-glucamine dithiocarbamate (BG.DTC) or sodium N-(4-methoxybenzyl)-D-glucamine dithiocarbamate (MeO.BG.DTC), 24 h after Cd injection, efficiently mobilized Cd from hepatic SCF, apparently from cadmium-metallothionein (Cd-MT); MeO.BG.DTC also removed Cd from hepatic nuclear mitochondrial fraction. This treatment, however, increased the renal burden of Cd, indicating that the chelating agents, at least partly, transport Cd from the liver and possibly from other sites into the kidney. Three doses of the chelators further enhanced mobilization of Cd from hepatic as well as renal SCF, as corroborated by its enhanced urinary and, to a greater extent, fecal excretion. Hepatic and renal MT were induced several-fold above normal after a single dose of Cd as well as single or repeated doses of BG.DTC or MeO.BG.DTC. Seventy-two hours after a Cd injection, the hepatic MT declined to half of the induced level while the renal MT remained elevated. Administration of BG.DTC or MeO.BG.DTC in Cd pre-treated rats produced an additive response in hepatic MT, but the response in renal MT was less than additive at one dose and slightly declined after three doses. Hepatic Zn and Cu and renal Zn increased on treatment with Cd but were depleted after a single or repeated injection of BG.DTC or MeO.BG.DTC in normal as well as in Cd pre-exposed animals. The results indicate that intracellular access of amphipathic dithiocarbamates effectively mobilizes MT-bound Cd, which is preferentially excreted in the feces, and helps avoid further burden on the kidney and consequent nephrotoxicity. Additionally, MeO.BG.DTC was a better inducer of hepatic MT to help increased capture of toxic metal from the initial circulation and consequent toxicity.     

The longitudinal distribution of cadmium, zinc, copper, iron, and metallothionein in the small-intestinal mucosa of rats after administration of cadmium chloride

Different routes of Cd intake may influence the intestinal distribution of Cd, metallothionein (MT), and trace metals differently. Therefore, we compared the effects of parenteral and enteral administration of Cd on the distribution of trace metals and MT along the small intestine. In a first experiment three groups of rats were employed: a control, one receiving CdCl2 within the drinking water, and another receiving sc injections of CdCl2. In a second experiment, rats were fed three different diets with either 0, 0.3, or 1 mmol CdCl2/kg for one and two weeks to study the time- and dose-dependent effects of orally administered Cd. Metal concentrations (Cd, Zn, Cu, Fe) were measured by atomic emission spectrometry and MT was determined by radioimmunoassay. Intestinal MT levels did not show proximodistal gradients in controls or after sc administration of Cd, but orally administered Cd increased mucosal MT levels longitudinally from the duodenum to the ileum. Cd levels paralleled those of MT. Compared with the metal concentrations in the controls, sc administration of Cd did not change intestinal Zn, Cu, and Fe levels. Oral administration of Cd, however, increased Cu and decreased Fe levels in the intestinal mucosa significantly. The second experiment revealed that only high dietary concentrations of Cd increase intestinal Cd and MT levels longitudinally toward the distal parts, whereas at lower dietary concentration the longitudinal distribution was reversed. This shows that different routes and doses of Cd intake lead to a different trace metal and MT distribution and emphasizes the role of dietary Cd in the local induction of small-intestinal MT.     

Accumulation of orally given cadmium in Long-Evans Cinnamon (LEC) rats with an inherently abnormal copper metabolism

An inherent defect of biliary Cu excretion and subsequent Cu deposition in the liver have been found in Long-Evans Cinnamon (LEC) rats, which are promising models of Wilson disease. LEC and Fischer rats were given water containing Cd (CdCl2) at a level of 5 ppm for 30 days. Regardless of drinking Cd water, LEC rats showed a very high concentration of Cu (200 to 250 microgram/g) and Cu-metallothionein (Cu-MT) (18 mg/g) in the liver. There was no difference of Cd accumulation in the liver between the two strains exposed to Cd (2.6 and 2.7 microgram/g in the Fischer and LEC groups, respectively). However, the renal Cd concentration was slightly but significantly higher in LEC rats (3.5 microgram/g) than in Fischer rats (2.0 microgram/g). The ratio of renal Cd contents to the sum of renal and hepatic Cd contents was significantly higher in LEC rats (0.25) than in Fischer rats (0.15). The serum Cd concentration in Cd-treated LEC rats increased threefold compared to Cd-treated Fischer rats. It seems likely that Cd from the liver is transported into the kidney in the form of Cd, Cu-MT. There was no difference in uptake of Cd in the hepatic MT fraction between the two strains. Although biliary Cu excretion in LEC rats was significantly lower than that in Fischer rats, reduced excretion of Cd into bile was not found in LEC rats. The gross amounts of Cu and Cu-MT influenced the accumulation of Cd in the kidney rather than in the liver when Cd was given orally at a low level to LEC rats. Our results suggest tht Cu and Cd do not share the same sites of hepatobiliary excretion in rats, although the main route of their excretion is via bile.     

Acute cadmium exposure and ovarian steroidogenesis in cycling and pregnant rats

The purpose of this study was to evaluate the effect(s) of acute in vivo cadmium (Cd) exposure on steroidogenesis in rat ovaries during different reproductive states. Sprague-Dawley rats were injected subcutaneously on the day of diestrus, or on day 7 or 16 of gestation with a single dose of 0, 3, or 5 mg Cd/kg bw, and evaluated 24 h later. Serum progesterone and estradiol concentrations were determined. Whole-ovary culture was used to evaluate Cd effects on the production of progesterone, testosterone, and estradiol. Liver, kidney, spleen, ovary, placenta, and blood were analyzed for Cd and iron (Fe) concentrations. No general toxic effects, no disruption of estrous cyclicity, and no change in fetal viability were seen. Histologic evaluation revealed moderate Cd-related thecal congestion in ovaries of pregnant rats. The highest Cd concentrations, except for liver, were found in the fetal portion of the placenta. Interestingly, Cd-related decreases in Fe concentration were found in several tissues from rats in proestrus and on gestation day 8, and in fetal placenta from rats on gestation day 17. Cadmium appears to interfere with normal steroidogenesis at a number of sites in the biosynthetic pathway with serum estradiol concentration and ovarian estradiol production the most affected. Acute Cd effects on steroidogenesis are most severe in rats evaluated in proestrus or in early pregnancy, while in late pregnancy steroidogenesis is relatively unaffected.     

Plasma trace element (Se, Zn, Cu) concentrations in maternal and umbilical cord blood in Poland. Relation with birth weight, gestational age, and parity

Selenium (Se), copper (Cu), and zinc (Zn) concentrations were determined in plasma of 64 mothers at delivery, 58 nonpregnant women, 64 neonates, and 12 infants, aged 2-12 mo. Se and Zn concentrations in mothers at delivery were significantly lower, and Cu higher than in nonpregnant women. Mean Se and Cu concentrations in newborns were statistically lower than those in mothers at delivery, and Zn and Cu concentrations in preterm infants (n = 13) were significantly higher than in fullterm infants (n = 51). Maternal parity had no significant influence on the distribution of plasma trace element levels. No significant differences were observed in Se and Zn levels in maternal and cord blood plasma according to birth weight, contrary to maternal Cu concentration. Significant correlations were found between maternal and cord blood Se content, and between maternal plasma Cu concentration and birth weight of neonates.     

Effects of lateral hypothalamic lesions on placentophagia in virgin, primiparous, and multiparous rats.

Produced lesions of the lateral hypothalamus (LH) in 25 pregnant and 25 nonpregnant Sprague-Dawley rats through chronically implanted electrodes to investigate the effect of LH damage on placentophagia. Other variables investigated were prior parturitional experience and stimulus properties of the placenta. Lesions were produced under either anesthesia 24 hr prior to parturition in pregnant Ss and 24 hr prior to placenta presentation in nonpregnant Ss. Lesions produced aphagia to a liquid diet. Pregnancy was not a significant variable in the initiation of placentophagia, but prior parturitional experience was critical. Virgin and primiparous Ss did not exhibit placentophagia following LH damage, but multiparous Ss would eat placenta whenever the opportunity arose, independently of LH damage and pregnancy. (18 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Serum leptin levels do not rise during pregnancy in age-matched rats

The serum leptin profile and its production in adipose tissue during pregnancy and lactation were investigated along with changes in appetite and factors reflecting nutritional status in 11-week-old rats. Serum leptin levels in pregnant rats were stable except on day 20 of pregnancy and significantly reduced during lactation compared to nonpregnant rats (P < 0.001). Circulating leptin levels corresponded with changes in appetite during pregnancy and postparturition. Leptin mRNA in parametrial adipose tissue reflected the circulating levels, also being significantly reduced during late pregnancy and during lactation (P < 0.05). Leptin mRNA expression was observed in placenta, but the amount suggested little influence on circulating leptin levels. These results indicate that reduction in leptin mRNA in parametrial adipose tissue and circulating leptin levels may increase appetite during late pregnancy and lactation and may play a role in regulating metabolic homeostasis around parturition in rats.     

Identification and partial characterization of Arkansas isolates of chicken anemia virus

BACKGROUND: The underlying mechanism of enhanced antinociceptive effects and increased susceptibility to local anesthetics during pregnancy is not known. Mechanical, hormonal, biochemical, and neural changes have been suggested. The authors measured the susceptibility of individual spinal root axons to bupivacaine during late pregnancy in rats and compared them with similar measurements in nonpregnant rats. METHODS: Lumbar dorsal and ventral roots were excised from anesthetized pregnant and nonpregnant rats. Single-fiber dissection and recording techniques were used to isolate activity in individual axons. Supramaximal constant voltage stimuli were delivered to the distal end of the root. During in vitro perfusion, each root was exposed to increasing concentrations of bupivacaine, and the minimum blocking concentration (Cm) and the concentration that increased conduction latency by 50% (EC50) were measured. RESULTS: Myelinated and unmyelinated dorsal and ventral root axons of pregnant rats appeared to be less sensitive to steady-state conduction block and to the latency-increasing effects of bupivacaine than were equivalent axons from nonpregnant rats. Although when comparing specific axon types, only the difference in C-fibers was significant (Cm = 29.8 microM for pregnant and Cm = 22.1 microM for nonpregnant rats, P < 0.05; EC50 = 19.9 microM and 13.6 microM, respectively). CONCLUSIONS: In contrast to clinical expectations, the susceptibility to bupivacaine conduction block in individual dorsal and ventral root axons during late pregnancy in rats was not greater in pregnant animals. Pregnancy-related changes in diffusion barriers and activation of endogenous analgesic systems without changes in the electrophysiologic properties of spinal root axons are suggested as possible explanations for the discrepancy between clinical and experimental observations.     

Sputum eosinophilia is more closely associated with airway responsiveness to bradykinin than methacholine in asthma

OBJECTIVE: We investigated the change in the plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, in early-, mid-, and late-gestation normotensive pregnancies and in gestational age-matched preeclamptic pregnancies and compared the observed changes with changes in blood pressure. STUDY DESIGN: Blood pressure and peripheral plasma asymmetric dimethylarginine concentrations were measured in 20 nonpregnant and 145 pregnant women (33 first-trimester, 50 second-trimester, and 44 third-trimester normotensive pregnancies and 18 third-trimester pregnancies complicated by preeclampsia). In 23 normotensive pregnancies serial plasma asymmetric dimethylarginine concentrations were measured. Statistical analysis was by analysis of variance and linear regression. RESULTS: The blood pressures recorded throughout normal pregnancy were significantly lower than in nonpregnant subjects (p < 0.0001). The mean systolic, diastolic, and average blood pressures were significantly higher in the second-trimester groups than in the first-trimester groups, whereas in the third trimester average and diastolic blood pressures were significantly higher than in the second trimester. The mean (+/-SD) systolic and diastolic blood pressures in third-trimester preeclamptic patients was 157.7 +/- 11.2 and 110.9 +/- 8.5 mm Hg. The mean plasma asymmetric dimethylarginine concentration in nonpregnant women was 0.82 +/- 0.31 micromol/L (significantly higher than in normotensive pregnancy, p < 0.0001). The plasma asymmetric dimethylarginine concentration was also significantly higher in second-trimester than in first-trimester normotensive groups (respectively, 0.52 +/- 0.20 micromol/L and 0.40 +/- 0.15 micromol/L, p = 0.001) and was higher in third-trimester normotensive pregnancy 0.56 +/- 0.23 micromol/L than it was in the second trimester. The asymmetric dimethylarginine concentration in third-trimester preeclamptic patients was 1.17 +/- 0.42 micromol/L (p < 0.0001 vs normotensive third-trimester subjects). CONCLUSIONS: It is well recognized that blood pressure falls in early normal pregnancy and rises again toward term. These studies show that the early fall in blood pressure is accompanied by a significant fall in the plasma asymmetric dimethylarginine concentration. Later in pregnancy circulating concentrations increase and, when pregnancy is complicated by preeclampsia, concentrations are higher than in the nonpregnant state. Our data support a role for both asymmetric dimethylarginine and nitric oxide in the changes in blood pressure seen in both normal and preeclamptic pregnancy.     

The effects of low dietary copper intake during pregnancy on physiological fluids and reproductive performance of first-litter gilts

Seven pairs of first littermate gilts were used to study the influence of low copper supply and pregnancy on physiological fluids and reproductive performance of first-litter gilts. They were fed semi-purified diets containing either 2.13 or 12.25 micrograms/kg of Cu from 30 days of gestation through two weeks of lactation. Low-Cu gilts had lower plasma Cu in early- and mid- gestation and farrowed piglets with lower plasma Cu and higher plasma Zn concentrations (p < 0.05). Plasma Fe and Mn concentrations were not affected by Cu supply (p > 0.05). Plasma Cu and Fe levels of newborn piglets were lower than those of their dams (p < 0.05) but this was not true for plasma Zn and Mn (p > 0.05). Low-Cu gilts had lower Cu and higher Zn content in colostrum and also lower Cu in milk than control gilts (p < 0.05). No significant differences were found in Fe and Mn levels in colostrum and milk between the two treatments (p > 0.05). Colostrum was richer in Cu and Zn than milk (p < 0.05) but not in Fe and Mn (p > 0.05). The low-Cu diet did not affect (p > 0.05) weight changes during pregnancy. The duration of parturition was shorter for low-Cu than for control gilts (3.19h vs. 5.71h, p < 0.05). Control gilts farrowed larger litters than low-Cu gilts (9.71 vs. 7.57 piglets, p < 0.05). There were no significant differences in live litter weights at birth, one wk. or two wks. of age (p > 0.05). The results indicated that a low-Cu diet and pregnancy had some effect on plasma, colostrum and milk mineral concentrations, as well as on litter size of gilts. An interaction between Cu and Zn was found.     

Rheumatology research. Analysis of Spanish papers published in 1990-1996 in 9 foreign journals in the field

The organization of the human metallothionein (MT) gene family is more complex than the commonly used mouse and rat models. The human MTs are encoded by a family of genes consisting of 10 functional and 7 nonfunctional MT isoforms. One objective of this study was to determine if the accumulation of MT protein in cultures of human proximal tubule (HPT) cells exposed to metals is similar to that expected from the knowledge base obtained from rodent models. To accomplish this objective, HPT cells were exposed to both lethal and sublethal concentrations of Cd2+, Zn2+, Cu2+, Ag2+, Hg2+, and Pb2+ and MT protein levels were determined. The results were in general agreement with animal model studies, although there were some exceptions, mainly in areas where the animal model database was limited. In clear agreement with animal models, Cd2+, Zn2+, and Cu2+ were demonstrated to be potent inducers of MT protein accumulation. In contrast to the similarity in MT protein expression, we obtained evidence that the human renal MT-2 gene has a unique pattern of regulation compared to both animal models and human-derived cell cultures. In the present study, we determined that MT-2A mRNA was not induced by exposure of HPT cells to Cd2+ or the other metals, a finding in contrast to studies in both animal models and other human cell culture systems in which a high level of MT-2 mRNA induction occurs upon exposure to Cd2+ or Zn2+. While MT protein expression may be similar between humans and animal models, this finding provides initial evidence that regulation of the genes underlying MT protein expression may be divergent between species.     

Concentrations of leptin in the serum of pregnant, lactating, and cycling rats and of leptin messenger ribonucleic acid in rat placental tissue

Leptin concentrations were measured in the serum of cycling, pregnant, and lactating Sprague-Dawley rats. Serum leptin concentrations did not vary significantly during the estrous cycle. In contrast, as gestation advanced, serum leptin concentrations increased significantly, p < 0.0001. Following delivery, leptin concentrations declined and remained stable during lactation. Leptin messenger ribonucleic acid (mRNA) was identified in the visceral adipose tissue and placenta of rats sacrificed on days 14 and 21 of pregnancy. The relative abundance of placental leptin mRNA increased approximately 4 to 5 fold from day 14 to 21 of gestation. The pattern of elevated leptin concentrations in the serum of late pregnant rats is similar to that reported in pregnant women, therefore the rat may be a useful model for the study of leptin during pregnancy. The increase in leptin in the serum of late pregnant rats, as well as an increase in placental mRNA, raises the possibility that leptin may serve a physiological role for the late parturient rat and/or its young.     

Adrenomedullin, a new vasoactive peptide, is increased in preeclampsia

Adrenomedullin is a novel peptide that elicits a long-lasting vasorelaxant activity. Recently, we found high concentrations of adrenomedullin in maternal and umbilical cord plasma and in amniotic fluid in full-term human pregnancy, indicating a role of this peptide during gestation. To investigate the possibility that adrenomedullin is involved in the pathophysiology of preeclampsia, we measured its concentration in maternal and fetoplacental compartments. We studied 12 normotensive nonpregnant women, 13 hypertensive nonpregnant subjects, 29 patients with preeclampsia, and 30 normotensive pregnant women. In all patients, plasma was collected from the cubital vein, and amniotic fluid samples were obtained by transabdominal amniocentesis or at elective cesarean section. Plasma samples from umbilical vein and placental tissues were collected at delivery. Adrenomedullin was assayed on plasma and amniotic fluid samples using a specific radioimmunoassay, and its localization and distribution on placental sections was determined by immunohistochemistry. Adrenomedullin concentrations were higher in hypertensive than in normotensive nonpregnant patients. Pregnant women had higher adrenomedullin levels than nonpregnant subjects, although maternal plasma adrenomedullin concentrations did not differ between normal pregnant and preeclamptic women. Preeclamptic patients showed higher concentrations (P<0.01) than normotensive pregnant women of adrenomedullin in amniotic fluid (252+/-29 versus 112+/-10 fmol/ micromol creatinine) and umbilical vein plasma (18.1+/-2.1 versus 8. 5+/-1.1 fmol/mL). Increased local production of adrenomedullin is associated with preeclampsia. The fetus seems to be responsible for the higher levels of this hormone. Increased adrenomedullin concentrations may be necessary to maintain placental vascular resistance and/or fetal circulation at a physiological level.     

Differential induction of metallothionein synthesis by interleukin-6 and tumor necrosis factor-alpha in rat tissues

Metallothionein (MT) synthesis induced by the inflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF), was studied in vivo. Administration of recombinant human IL-6 or TNF to rats caused the acute phase responses including rapid decreases in plasma zinc (Zn), and increases in plasma copper (Cu) and ceruloplasmin. Hepatic concentration of MT-I, one of MT isoforms, began to increase within 3 h after the injection of IL-6 or TNF. In IL-6-treated rats, MT-I concentration in liver reached a maximum level at 12 h and decreased with a transient rebound, whereas, in TNF-treated rats, a high level of MT-I lasted for about 48 h. MT-II, the other MT isoform, was induced more than MT-I in liver by both cytokines. MT-I was also induced in lung and heart by TNF, but little by IL-6. The data suggest that IL-6 may be responsible for MT synthesis in liver, whereas TNF may be responsible not only in liver but also in lung and heart. Furthermore plasma concentration of MT did not always reflect the enhanced concentration of MT by TNF and IL-6 in liver, suggesting involvement of many factors influencing plasma MT levels. The interrelation between IL-6 and TNF for MT synthesis has also been discussed.     

Zinc levels in the rat fetal liver are not determined by transport across the placental microvillar membrane or the fetal liver plasma membrane

During pregnancy, zinc (Zn) levels in the rat fetal liver increase markedly. Why they do so or how the increase is regulated is unknown. We firstly investigated whether the increase occurs as a result of increased Zn transfer across the placenta and then tested whether the regulation occurred at the level of the microvillar membrane of the placenta or the fetal liver plasma membrane. Rats at different stages of gestation were injected with 7.5 microCi 65Zn in 100 microliters rat serum and killed after 1 h. 65Zn levels in the fetus remained constant at equivalent to the amount in 50 microliters maternal plasma per fetus until Day 18; at this time they increased to equivalent to 1.33 ml and then continued to increase until term. We isolated placental microvillar vesicles from placentas at each stage of gestation, characterized them, and measured Zn uptake. Zn uptake rates did not change during pregnancy. Similarly, we isolated vesicles from fetal liver plasma membrane and measured Zn uptake. Again, the uptake properties did not change during pregnancy. The data suggest that some other step in the transport process is rate limiting and that the increase in Zn levels in the fetal liver that occurs during pregnancy is possibly a result, rather than a cause, of metallothionein induction.     

Quinine pharmacokinetics in young children with severe malaria

In this study, we determined selenium concentrations in serum samples of healthy women (146 pregnant and 74 nonpregnant) living in the Mediterranean area of the coast of Granada (southeast Spain). The subjects were distributed in two groups: group A (pregnant women), divided into three categories according to the trimester of pregnancy, and group B (nonpregnant women). No significant differences were observed in the selenium levels either among pregnant women according to the trimester of pregnancy or in the group of nonpregnant women. No other significant differences were determined as regards the age of pregnant women (P > 0.05). Serum selenium levels are slightly lower during pregnancy. Considering that serum selenium levels affect the body selenium status, the concentrations determined establish the non-existence of selenium problems in the daily dietary intake with respect to maternal and fetal necessities during pregnancy.     

Effects of head-down tilt on atrial natriuretic peptide and the renin system in pregnancy

We studied the effects of head-down tilt to 10 degrees for 30 minutes on plasma atrial natriuretic peptide and the renin-aldosterone system in 8 preeclamptic pregnant women, 8 healthy pregnant women, and 11 nonpregnant women of fertile age. Mean arterial blood pressure did not change in the pregnant groups but increased significantly in the nonpregnant control subjects. Heart rate decreased significantly in preeclamptic women but remained unchanged in both control groups. Baseline atrial natriuretic peptide concentration was significantly higher in both preeclamptic (66 +/- 4 pmol/L) and pregnant (54 +/- 6 pmol/L) control subjects compared with nonpregnant subjects (40 +/- 2 pmol/L), but the difference between the pregnant groups was not significant. Head-down tilting induced a significant increase in atrial natriuretic peptide only in healthy pregnant women. Baseline plasma renin activity and aldosterone concentrations were significantly higher in pregnant control subjects compared with both the preeclamptic and nonpregnant groups. The differences between the preeclamptic and nonpregnant control groups were nonsignificant. After head-down tilting, plasma renin activity decreased significantly only in nonpregnant control subjects, whereas aldosterone decreased significantly in preeclamptic and nonpregnant control subjects. In preeclampsia, atrial natriuretic peptide release followed blood pressure and not changes in cardiac output. When all 27 women were studied, a correlation between atrial natriuretic peptide and mean arterial pressure was found in the left lateral supine position. The results suggest that pregnant women developing preeclampsia lose their usual hemodynamic control and show reactions resembling the nonpregnant state when subjected to head-down tilt.     

Changes in myocardial metallothionein on isoproterenol-induced myocardial injury

The amounts of myocardial metallothionein (MT) and heavy metal (Zn, Cu) levels during the early stage of the experimental myocardial infarction model induced by isoproterenol (Isp) administration were measured by an atomic absorption spectrophotometry. MT was measured by the Cd-hem method. Myocardial infarction was induced by the administration of 75 mg/kg i.p. of Isp to rats weighing 270 +/- 10 g. Thirty minutes after Isp injection, Zn and Cu levels began to decrease and 12 h later, reached the minimal values compared with the control value. The level of MT began to increase 3 h after the Isp injection and reached the maximal value at 12 h, although MT remained undetectable in the control myocardial tissue by the Cd-hem method. MT levels in the liver increased and total Zn and Cu were elevated compared with the control value 12 h after Isp administration. These results suggest that MT is produced in the myocardium after Isp administration, and that the roles of MT in the heart and the liver are different. It was thought that a rise in MT was induced for the protection of the myocardial cells to injury.