Biomedical subjects

Lucilla Poston

Publications and source records attributed to Lucilla Poston.

At least 37 records · Page 2Linked to original sources

PubMed2004

Impaired glucose homeostasis and mitochondrial abnormalities in offspring of rats fed a fat-rich diet in pregnancy.

We previously reported that prenatal and suckling exposure to a maternal diet rich in animal fat leads to cardiovascular dysfunction in young adult rat offspring with subsequent development of dyslipidemia and hyperglycemia. We have further investigated glucose homeostasis in adult female offspring by euglycemic-hyperinsulinemic clamp and by dynamic assessment of glucose-stimulated insulin secretion in isolated, perifused pancreatic islet cells. Additionally, given the link between reduced mitochondrial DNA (mtDNA) content and the development of type 2 diabetes mellitus, we have measured mtDNA in organs from young adult animals. Sprague-Dawley rats were fed a diet rich in animal fat or normal chow throughout pregnancy and weaning. Infusion of insulin (5 mU.kg(-1).min(-1)) resulted in a higher steady-state plasma insulin concentration in 1-year-old offspring of fat-fed dams (OHF, n = 4) vs. offspring of control dams (OC, n = 4, P < 0.01). Glucose-stimulated insulin secretion in isolated islets from 9-mo-old OHF was significantly reduced compared with OC (n = 4, P < 0.05). Transmission electron micrography showed altered insulin secretory granule morphology in OHF pancreatic beta-cells. Kidney mtDNA was reduced in 3-mo-old OHF [16S-to-18S gene ratio: OC (n = 10) 1.05 +/- 0.19 vs. OHF (n = 10) 0.66 +/- 0.06, P < 0.05]. At 6 mo, gene chip microarray of OHF aorta showed reduced expression of the mitochondrial genome. Prenatal and suckling exposure to a diet rich in animal fat leads to whole body insulin resistance and pancreatic beta-cell dysfunction in adulthood, which is preceded by reduced tissue mtDNA content and altered mitochondrial gene expression.

Adipose Tissue↗

PubMed2004

Predictive adaptive responses to maternal high-fat diet prevent endothelial dysfunction but not hypertension in adult rat offspring.

BACKGROUND: Population-based studies suggest that fetal adaptive responses to maternal dietary imbalance confer survival benefit when the postnatal diet remains suboptimal but increase susceptibility to cardiovascular disease when postnatal nutrition is improved. We have investigated "predictive adaptive" responses in a rodent model in which adult offspring of fat-fed dams develop characteristics of the metabolic syndrome. METHODS AND RESULTS: Sprague-Dawley rats were fed a fat-rich diet or normal chow throughout pregnancy and weaning. Vascular endothelial function and blood pressure were determined in 180-day-old offspring of fat-fed dams raised on standard chow (FC) or on the fat-rich diet (FF) and in offspring of chow-fed dams raised on chow (CON). Small mesenteric artery endothelium-dependent dilation to acetylcholine was impaired in male and female FC (by ANOVA, P<0.001 versus CON) but similar to CON in FF (P=NS). Blood glucose was lower in FF versus FC. Heart rate was reduced in male FC versus CON (P<0.05) but not in FF. Plasma triglyceride concentrations were reduced in male FF compared with CON (P<0.05). Blood pressure was raised in female FC (systolic, 132.5+/-3.0 mm Hg versus CON, 119.0+/-3.8 mm Hg, P<0.05; diastolic, 91.2+/-1.7 mm Hg versus CON, 81.1+/-1.4 mm Hg, P<0.05) and in female FF (systolic, 132.5+/-4.2 mm Hg versus CON, P<0.05; diastolic, 91.0+/-1.9 mm Hg versus CON, P<0.05). Blood pressure was similar to CON in male FC and FF. CONCLUSIONS: Predictive adaptive responses prevent endothelial dysfunction and reduced heart rate in offspring of fat-fed dams if offspring are raised on the same diet but do not prevent development of raised blood pressure.

Adaptation, Physiological↗

PubMed2004

Oxidative stress and preeclampsia: rationale for antioxidant clinical trials.

Preeclampsia remains a frequent and potentially dangerous complication of pregnancy. The cause remains largely unknown, but oxidative stress and a generalized inflammatory state are features of the maternal syndrome. The placenta appears to be the principal source of free radical synthesis but maternal leukocytes and the maternal endothelium are also likely contributors. Recent reports have suggested an important role for placental trophoblast NAD(P)H oxidase in free radical generation in preeclampsia. The antioxidant vitamin E is now known to have multiple actions in addition to prevention of lipid peroxidation (ie, inhibition of NAD(P)H oxidase activation and the inflammatory response). In view of the abnormally low plasma vitamin C concentrations in preeclampsia, a combination of vitamins C and E is a promising prophylactic strategy for prevention of preeclampsia. Several multicenter randomized clinical trials are now underway. The potential use of antioxidants and the recognized, albeit modest, benefit of low-dose aspirin prophylaxis have heightened the need for a reliable predictive test for preeclampsia. A combination test involving several relevant biomarkers is likely to provide the best predictive potential.

Antioxidants↗

PubMed2004

Glutathione S-transferase and liver function in intrahepatic cholestasis of pregnancy and pruritus gravidarum.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with poor maternal and fetal outcome. The diagnosis is based on pruritus with abnormal liver function in the absence of other pathological conditions. However, pruritus in pregnancy is common, and it may be the only presenting feature in ICP. No reliable test currently exists that can discriminate between those women destined to develop ICP and those with the benign condition of pruritus gravidarum (PG). The purpose of this prospective study was to investigate longitudinally the serum concentration of glutathione S-transferase alpha (GSTA, a specific marker of hepatocellular integrity) and to compare this with the temporal profile of conventional liver function markers in women with ICP (n = 63), PG (n = 43), and normal pregnant controls (n = 26). Blood was sampled on at least 3 separate occasions between 16 weeks of gestation and 4 weeks postpartum. Serum concentrations of GSTA increased with gestation in ICP, being significantly higher from 24 (+/-2) weeks compared with controls (400% difference; 95% CI, 240%-734%; P < .001). GSTA was also higher in ICP versus PG (433% difference; 95% CI, 228%-790%; P < .001) throughout the gestational period studied. Significant differences in the ICP compared with control and PG groups were also found for total bile acids, alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase and alkaline phosphatase. In conclusion, the measurement of GSTA provides a test of liver dysfunction that distinguishes women with ICP from those with PG. Additionally, on the basis of this study, reference ranges for biochemical markers of liver function require reevaluation in pregnancy.

Adult↗

PubMed2004

Diet-induced obesity in the rat: a model for gestational diabetes mellitus.

OBJECTIVES: Obesity is one of the most important risk factors for the development of gestational diabetes mellitus (GDM). However, in obese women, it is difficult to disentangle the genetic and environmental contributions. The aim of this study was to investigate whether diet-induced obesity results in GDM in rats with the same genetic background. STUDY DESIGN: Female Wistar rats were fed a cafeteria-style diet (CAF) or the standard control (C) diet from 70 days of age onward. After 4 weeks on the diets, subgroups of CAF and C rats were mated. In virgin and late-pregnant CAF and C rats, we determined body weight, body composition by dual-energy x-ray absorptiometry (DEXA), glucose tolerance by intravenous glucose tolerance test (IVGTT), and insulin sensitivity by hyperinsulinemic euglycemic clamp in nonanesthesized rats. Plasma leptin concentrations were also measured. RESULTS: Body weight increased after 4 weeks in virgin CAF rats (P<.0001) and exceeded that of C rats throughout pregnancy. This resulted exclusively from increased fat mass, as determined by DEXA, and was associated with a rise in plasma leptin concentrations in nonpregnant and pregnant (both P<.0001) CAF rats. During the IVGTT, nonpregnant CAF rats showed normal glucose levels but increased insulin levels compared with C rats (P<.05 for the area under the curve for insulin: AUC(insulin)). In pregnant CAF animals, glucose tolerance was clearly impaired (AUC(glucose): P<.001) with insulin also raised (AUC(insulin): P<.05). On day 22, fetal weight was comparable between C and CAF rats, but litter weight was higher in CAF rats (P<.05) owing to an increase in litter size. Hyperinsulinemic clamp studies revealed unequivocal insulin resistance in nonpregnant CAF rats, which was aggravated by pregnancy, the proportional effect of obesity being higher than that of pregnancy. CONCLUSION: Diet-induced obesity in rats is associated with glucose intolerance during pregnancy but not in the nonpregnant state. This is likely to result from the additive effects of obesity and pregnancy on insulin sensitivity. This obese rat model is an attractive model to study further the physiologic and molecular abnormalities in GDM.

Animals↗

PubMed2004

Vitamin E in preeclampsia.

Preeclampsia is the disorder of pregnancy with the highest rate of both maternal and neonatal morbidity and mortality. The maternal syndrome is characterized by oxidative stress and activation of the vascular endothelium that may originate from placental release of lipid peroxidation products, cytokines, and microparticles leading to an acute inflammatory response. The current understanding of the etiology has allowed the improvement of predictive tests, tests that could make intervention possible from early pregnancy onwards. Although the large secondary intervention antioxidant trials in cardiovascular diseases did not show any beneficial effect of vitamin E and vitamin C, either alone or in combination, knowledge of the nature of the pathogenesis of preeclampsia offers hope for the beneficial use of antioxidants in the prevention of the disorder. Not only has our previous small trial shown that antioxidant prophylactics in high-risk women lowered the prevalence of preeclampsia, but also new evidence has demonstrated multiple other actions of alpha-tocopherol (such as anti-inflammation and inhibition of NAD(P)H oxidase activation) besides its antioxidant properties that could be advantageous in the prevention of the disorder. Several larger trials are under way to investigate the precise role that vitamins C and E can play in the prevention of preeclampsia.

Antioxidants↗

PubMed2003

Effect of nutritional restriction in early pregnancy on isolated femoral artery function in mid-gestation fetal sheep.

Unbalanced maternal nutrition affects fetal endocrine and cardiovascular systems, sometimes accompanied by changes in growth, although this is usually in late gestation. We determined the effect of moderate restriction for the first half of gestation of maternal dietary protein, or of total calorific intake on isolated resistance artery function of mid-gestation fetal sheep. Welsh Mountain ewes were nutritionally restricted by 30 % of the recommended nutrient intake (globally restricted) or 30 % of the recommended protein intake (protein-restricted), compared to control ewes fed 100 % of recommended nutrient intake, for ~12 days prior to conception and for the subsequent 70 days of gestation. At mid-gestation, fetal and placental weights were similar in all dietary groups. In isolated femoral arteries, the response curve to noradrenaline was reduced in protein-restricted group fetuses (P < 0.05). Maximal relaxation (P < 0.01) and sensitivity (P < 0.05) to acetylcholine were markedly reduced in protein-restricted group fetuses, and to a smaller extent in globally restricted group fetuses (response curve, P < 0.05). The dilator response (P < 0.05) and sensitivity (P < 0.05) to the alpha2 agonist UK14304 was lower in protein-, but not in globally restricted group fetuses. The response (P < 0.05) and sensitivity (P < 0.05) to the nitric oxide donor sodium nitroprusside were reduced in protein-restricted group fetuses compared to controls. Our data show that dietary imbalance, in particular restricted protein, of the ewe can produce blunting of endothelial-dependent and -independent relaxation in systemic arteries from the mid-gestation fetus. These changes may precede perturbed late-gestation fetal and postnatal cardiovascular control.

3-Hydroxybutyric Acid↗

PubMed2003

Dietary protein restriction in pregnancy induces hypertension and vascular defects in rat male offspring.

It is established that dietary protein restriction of pregnant rats results in their offspring developing hypertension. However, to date no studies have investigated peripheral vascular function of offspring using the low protein model. Therefore, the aim of the study was to assess isolated resistance artery function from adult male offspring of control (C, 18% casein) and protein-restricted (PR, 9% casein) pregnant dams at two different ages. The birthweight of PR offspring did not significantly differ from that of C offspring. Systolic blood pressure was significantly elevated in PR compared with C (p < 0.05). Maximal vascular contraction to phenylephrine and the thromboxane analog U46619 were similar in C and PR offspring at postnatal d 87 and 164. Relaxation induced by the endothelium-dependent vasodilators acetylcholine or bradykinin was significantly reduced in the PR group (p < 0.05). Relaxation to the endothelium-independent vasodilator sodium nitroprusside and phosphodiesterase type 3 inhibitor cilostamide was less in the PR offspring compared with C (p < 0.01). Dietary protein restriction in pregnancy induces hypertension and vascular dysfunction in male offspring. Abnormalities in the nitric oxide-cGMP pathway may explain the defect in endothelium-dependent and -independent relaxation. Reduced vasodilation may be a potential mechanism underlying the elevated systolic blood pressure observed in this model.

Animals↗

PubMed2003

Longitudinal evaluation of markers of endothelial cell dysfunction and hemostasis in treated antiphospholipid syndrome and in healthy pregnancy.

OBJECTIVE: The purpose of this study was to determine whether primary antiphospholipid syndrome pregnancies are associated with endothelial cell activation in the maternal circulation. STUDY DESIGN: Markers of endothelial cell activation were measured every 4 weeks during pregnancy in the blood of 23 women with primary antiphospholipid syndrome and 19 control subjects. All women with antiphospholipid syndrome received anticoagulant treatment. Plasma concentrations of plasminogen activator inhibitor type 1, tissue plasminogen activator, soluble intercellular adhesion molecule-1, vascular cell adhesion molecule-1, E-selectin, and soluble thrombomodulin were determined by enzyme-linked immunoassay. Concentrations of prothrombin fragments 1+2 and D-dimers were also determined. RESULTS: Three antiphospholipid syndrome pregnancies (13%) were complicated by intrauterine growth restriction and preeclampsia; one antiphospholipid syndrome pregnancy (4%) was complicated by preterm rupture of membranes. Six women with antiphospholipid syndrome (26%) had thrombotic events. Differences in concentrations of endothelial cell activation markers between antiphospholipid syndrome and control pregnancies were not significant. CONCLUSION: Despite poorer pregnancy outcome, there was no evidence of greater endothelial cell activation in antiphospholipid syndrome pregnancies that were treated.

Anticoagulants↗

PubMed2003

Longitudinal analysis of serum insulin-like growth factor-I and insulin-like growth factor binding protein-1 in antiphospholipid syndrome and in healthy pregnancy.

OBJECTIVE: The purpose of this study was to determine the concentrations of serum insulin-like growth factor-I and insulin-like growth factor binding protein-1 in pregnancies that are complicated with primary antiphospholipid syndrome. STUDY DESIGN: Longitudinal blood samples were collected from 8 weeks of gestation in 28 women with treated primary antiphospholipid syndrome and 19 control women. Serum insulin-like growth factor-I and insulin-like growth factor binding protein-1 were measured by immunoradiometric assay. RESULTS: Three antiphospholipid syndrome pregnancies miscarried, four pregnancies had intrauterine growth restriction and preeclampsia, six pregnancies had a thrombotic event, and one pregnancy had abruptio placentae. Mean (+/-SD) birth weight in antiphospholipid syndrome group was 2867 +/- 914 g (control, 3492 +/- 527 g; P =.02), and the mean gestation at delivery was 36.5 +/- 5.2 weeks (control, 40.3 +/- 0.7 weeks; P =.002). Insulin-like growth factor binding protein-1 and insulin-like growth factor-I concentrations increased with gestational age in both groups (2.8% and 2.4% per week), but insulin-like growth factor binding protein-1 was 61% higher in the antiphospholipid syndrome group (95% CI, 16%-122%; P =.004). Insulin-like growth factor-I was not significantly different (8% higher in antiphospholipid syndrome; 95% CI, -10% to 30%; P =.41). CONCLUSION: Serum concentrations of insulin-like growth factor binding protein-1 are abnormal in the antiphospholipid syndrome group and may reflect abnormalities in trophoblast invasion.

Abortion, Spontaneous↗

PubMed2003

Gender-linked hypertension in offspring of lard-fed pregnant rats.

Epidemiological studies suggest an association between maternal nutrition and offspring cardiovascular disease. We previously demonstrated endothelial dysfunction and abnormal aortic fatty acid composition in adult female offspring of rats fed animal lard during pregnancy. We have now further investigated this model. Female Sprague-Dawley rats were fed a control breeding diet (5.3% fat) or a diet rich in lard (25.7% fat) 10 days before and throughout pregnancy and lactation. Male and female offspring were implanted with radiotelemeters for recording of blood pressure, heart rate, and activity at 80, 180, and 360 days of age. Reactivity to acetylcholine and to nitric oxide were assessed in isolated small mesenteric arteries from 80- and 180-day-old littermates. Systolic blood pressure (awake phase) was raised in female offspring (180 days: offspring of control, 130.7+/-1.6 mm Hg, n=5, versus offspring of lard-fed, 138.1+/-2.9, n=5, P=0.029; 360 days: offspring of control, 129.7+/-3.7 mm Hg, n=6, versus offspring of lard-fed, 142.1+/-3.2, n=6, P=0.005). Diastolic blood pressure was also raised at 180 days (offspring of control, 87.6+/-1.0 mm Hg, n=5, versus offspring of lard-fed, 94.7+/-2.6, n=5, P=0.011). Blood pressure was not raised in male offspring. Endothelium-dependent relaxation to acetylcholine was blunted in male and female offspring of lard-fed dams (80 and 180 days). Feeding a diet rich in lard to pregnant rats leads to gender-related cardiovascular dysfunction in normally fed offspring.

Animals↗

PubMed2002

Abnormalities in intracellular Ca2+ regulation in fetal vascular smooth muscle in pre-eclampsia: enhanced sensitivity to arachidonic acid.

Pre-eclampsia (PE) is a leading cause of maternal and fetal mortality and morbidity. As free fatty acid metabolism is abnormally regulated in PE, we investigated the intracellular Ca2+([Ca2+]i) response to arachidonic acid (AA) in primary cultures of human umbilical artery smooth muscle cells (HUASMC). AA (50 microM) caused a significantly greater [Ca2+]i elevation in PE than in normal HUASMC, with many cells displaying a delayed secondary increase. The nonmetabolizable AA analog ETYA did not induce a response, suggesting that the augmented PE response depends on an AA metabolite. Inhibition of the AA metabolizing cyclooxygenase or lipoxygenase pathways did not affect the AA response of PE HUASMC but induced in normal cells the secondary rise of [Ca2+]i observed in PE cells. This potentiated response and the response in PE cells were blocked by inhibitors of the monooxygenase pathway, a third AA metabolizing pathway. We conclude that the [Ca2+]i response of HUASMC is elevated in PE because of an increased level of a monooxygenase metabolite that stimulates Ca2+ influx and that this can be mimicked in normal cells by blocking cyclooxygenase or lipoxygenase to divert AA to the monooxygenase. This and our work with fetal endothelial cells (FASEB J. 10.1096/fj.01-0916fje) demonstrate phenotypic changes in the fetal vasculature in PE.

Arachidonic Acid↗

PubMed2002

Interleukin-1beta induces calcium transients and enhances basal and store operated calcium entry in human myometrial smooth muscle.

We have previously reported increased protein expression of sarcoplasmic reticulum calcium ATPase (SERCA) 2b in myometrium from women in labor at term, but the stimulus for this change is unknown. Proinflammatory cytokines have been implicated in the cascade of events leading to preterm and term labor, and we hypothesize that interleukin (IL)-1beta may induce changes in key calcium homeostatic mechanisms and, in turn, augment myometrial contractility before labor. The aim of the present study was to investigate the long-term effects of IL-1beta on SERCA 2b protein expression, calcium mobilization from intracellular stores, and store-operated calcium entry. Myometrial biopsies were obtained, with consent, from women undergoing elective cesarean section at term. Primary-cultured human myometrial smooth muscle (HMSM) cells were exposed to IL-1beta (10 ng/ml) for 24 h or to culture medium alone (control). Cells were subsequently used in Western blot studies or loaded with fura-2 to assess calcium dynamics using fluorescent digital imaging. The present study clearly demonstrated that IL-1beta significantly increased SERCA 2b protein expression in HMSM cells. Cyclopiazonic acid-induced calcium transients were also augmented, predominantly by activation of lanthanum-sensitive, store-operated calcium entry. HMSM cell excitability was enhanced, as evidenced by increased basal calcium entry and the initiation of spontaneous calcium transients in 37% of IL-1beta-treated cells. IL-1beta modulation of calcium mobilization may be an important mechanism in the cascade of events preparing the pregnant uterus for labor.

Adult↗

PubMed2002

Maternal protein restriction in the rat impairs resistance artery but not conduit artery function in pregnant offspring.

Dietary protein restriction during gestation has been shown to produce vascular dysfunction in pregnant rats and hypertension in their offspring. However, no studies have to date examined the effects of such 'programming' on the vascular function of female offspring when they in turn become pregnant. We have therefore studied isolated conduit and resistance artery function from pregnant female offspring of control (C, 18 % casein) and protein-restricted (PR, 9 % casein) pregnant dams. There were no differences in birth weight, weight gain during pregnancy, litter size, fetal weight, placental weight, fetal : placental weight ratio or organ weights between the C and PR groups. In isolated mesenteric arteries, the vasodilatation in response to the endothelial-dependent vasodilator acetylcholine (ACh) and the beta-adrenoceptor agonist isoprenaline was decreased in the PR group, while there were no differences in the constriction in response to potassium (125 mM) or the alpha1-adrenoceptor agonist phenylephrine (PE). No differences in any responses were seen in the isolated thoracic aorta. We conclude that dietary protein restriction in pregnancy programmes vasodilator dysfunction in isolated resistance arteries of female offspring when they become pregnant, but does not affect conduit arteries.

Acetylcholine↗

PubMed2002

Preeclampsia is associated with altered Ca2+ regulation and NO production in human fetal venous endothelial cells.

Preeclampsia (PE) is a leading cause of maternal hypertension in pregnancy, fetal growth restriction, premature birth, and fetal and maternal mortality (1). Activation and dysfunction of the maternal and fetal endothelium in PE may be the consequence of increased oxidative stress associated with circulating lipid peroxides (2-4), and in cases of severe maternal hypertension, uterine and umbilical artery waveforms are abnormal (5). We have investigated PE-associated abnormalities in the regulation of intracellular Ca2+ ([Ca2+]i) and cyclic guanosine monophosphate (cGMP) production (index of nitric oxide [NO]) in human fetal umbilical vein endothelial cells. Basal [Ca2+]i was slightly elevated in PE cells, whereas agonist-stimulated Ca2+ entry was reduced in cells from PE compared with normal term or age-matched preterm pregnancies. Furthermore, PE cells exhibited a decreased permeability to Ba2+ but an increased permeability to Mn2+ and Gd3+, suggesting that PE is associated with phenotypic alterations in fetal endothelial cation channel(s). Basal and histamine-stimulated cGMP levels were elevated in PE compared with preterm or normal cells, implying an increased NO production in PE. However, immunoblots for endothelial NO synthase (eNOS) and soluble guanylyl cyclase (sGC) revealed reduced eNOS expression in PE and preterm cells, with negligible changes in sGC levels. This study provides important and novel insights into abnormalities of fetal endothelial cells isolated from women with PE, reveal ing an altered cation membrane permeability and activity of eNOS-sGC pathway. As these changes are sustained in culture in vitro, this may reflect long-term "programming" of the fetal cardiovascular system.

Calcium↗

PubMed2002

Developmental changes in the functional characteristics and expression of voltage-gated K+ channel currents in rat aortic myocytes.

OBJECTIVE: Active control of the arterial diameter by vascular smooth muscle is one of the principle mechanisms by which vessels adapt to a significant rise in blood pressure after birth. Although voltage-gated K+ (Kv) channels play an important role in the regulation of excitation-contraction coupling in arteries, very little is known about postnatal modification of Kv channels. We therefore investigated changes in the functional characteristics and expression of Kv channels in rat aortic myocytes (RAMs) during early postnatal development. METHODS: Kv currents (I(Kv)) were investigated in single smooth muscle cells freshly dispersed from neonatal (1-3 days) and adult Wistar rat thoracic aorta using the whole-cell patch clamp technique. RESULTS: I(Kv) in neonates had significantly faster activation kinetics and was inactivated at more positive voltages than I(Kv) in adults (half-inactivation potential -24+/-2 and -40+/-3 mV and slope factor 4.2+/-0.4 and 11.1+/-0.5 mV, respectively). No difference in the steady state activation was found. I(Kv) in neonates was insensitive to a high concentration of tetraethylammonium (TEA, 10 mM) but blocked 4-aminopyridine (4-AP, IC(50)=0.5+/-0.1 mM), whereas I(Kv) in adult RAMs was almost completely abolished by 10 mM TEA and was relatively insensitive to low concentrations of 4-AP. I(Kv) in both age groups was insensitive to charybdotoxin (300 nM) or alpha-dendrotoxin (200 nM). Immunoblot analysis showed that the expression of Kv1.2 alpha-protein decreased and Kv2.1 increased with development. CONCLUSION: Significant changes in functional characteristics of the native I(Kv) and the expression of particular Kv channel proteins occurred during postnatal vascular development. These changes could play an important role in adaptation to extrauterine life.

4-Aminopyridine↗

PubMed2002

Leptin and preeclampsia.

Preeclampsia, a common complications of pregnancy, is associated with an increase in the concentration of leptin in the maternal blood, which precedes the clinical onset of the disease. This review addresses the potential sources of leptin and considers the possible consequences, although at present these are entirely conjectural. The placenta is likely to contribute to the rise in leptin, and placental hypoxia and inflammatory mediators may be important stimuli. The possible protective and damaging sequelae of an increase in the maternal leptin concentrations may range from beneficial stimulation of fetal growth to an increase in blood pressure through stimulation of sympathetic activity. Further research is needed to determine if the rise in leptin plays a role in preeclampsia or whether it is a secondary and unrelated bystander.

Embryonic and Fetal Development↗

PubMed2002

A longitudinal study of biochemical variables in women at risk of preeclampsia.

OBJECTIVE: The purpose of this study was to characterize gestational profiles of biochemical markers that are associated with preeclampsia in the blood of pregnant women in whom preeclampsia developed later and to compare these markers with the markers of women who were delivered of small-for-gestational-age infants without preeclampsia and with women who were at low risk for the development of preeclampsia. STUDY DESIGN: This was a prospective case control study. The subjects were women at risk of preeclampsia who were enrolled in the placebo arm of a clinical trial. Indices of antioxidant status, oxidative stress, placental and endothelial function, and serum lipid concentrations were evaluated from 20 weeks of gestation until delivery in 21 women in whom preeclampsia developed later, in 17 women without preeclampsia who were delivered of small-for-gestational-age infants, and in 27 women who were at low risk for the development of preeclampsia. RESULTS: Ascorbic acid was reduced early in preeclampsia and small-for-gestational-age pregnancies. Leptin, placenta growth factor, the plasminogen activator inhibitor (PAI-1)/PAI-2 ratio, and uric acid were predictive of the development of preeclampsia. CONCLUSION: Gestational profiles of several markers were abnormal in the group with preeclampsia, and some of the markers that may prove useful in the selective prediction of preeclampsia were identified.

Algorithms↗