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Biomedical subjects

Elena Casals

Publications and source records attributed to Elena Casals.

9 recordsLinked to original sources

First-trimester screening for trisomy 21 in twin pregnancy: does the addition of biochemistry make an improvement?

OBJECTIVE: To evaluate the effectiveness of the addition of first-trimester biochemistry to fetal nuchal translucency (NT) measurement in the Combined Test when screening for trisomy 21 in twin pregnancies. METHODS: Maternal serum free beta-hCG and PAPP-A were determined at 8 to 12 weeks and fetal NT was measured at 11 to 14 weeks. The individual risks were estimated for each of the fetuses using both NT screening alone and the Combined Test. An invasive diagnostic procedure was offered when the risk was 1:250 or over in either one of the fetuses. In the first period, only the results of NT screening were clinically applied. After previous analysis, the Combined Test was introduced into clinical practice. RESULTS: In the two-and-a-half-year study period, a complete follow-up was obtained in 100 twin pregnancies. Three fetuses (two pregnancies) with trisomy 21 were detected by both methods. The false-positive rate achieved by NT screening (14.3% of pregnancies and 8.6% of fetuses) was substantially reduced when first-trimester biochemistry was added in the Combined Test (5.1% of pregnancies and 3.6% of fetuses). CONCLUSION: The Combined Test appears to maintain the detection rate achieved by NT screening for trisomy 21 in twin pregnancies, but false-positive rates and invasive diagnostic procedures are reduced.

Adult↗

Atherogenic lipoprotein subfraction profile in preeclamptic women with and without high triglycerides: different pathophysiologic subsets in preeclampsia.

Abnormal lipid metabolism has been proposed as a pathogenic factor of preeclampsia, although whether it is a constant feature in all preeclamptic patients is unclear. We assessed whether plasma triglyceride (TG) levels can distinguish a subgroup of preeclamptic women with alterations in lipoprotein profile from those with normal lipid metabolism and can be used to identify 2 distinct pathogenic groups in preeclampsia. This prospective study included 34 women with preeclampsia and 23 healthy pregnant women. Preeclamptic women were further subclassified into normal-TG (<250 mg/dL) and high-TG (>or=250 mg/dL) groups on the basis of the 90th percentile in our population. Low-density lipoproteins (LDLs) were ultracentrifuged and were separated into 4 subfractions, and lipid distribution in the subfractions was analyzed in all study groups. Vascular cell adhesion molecule-1 was also measured as a marker of endothelial dysfunction. Sixteen women with preeclampsia had high TGs (47% vs 13% in control subjects, P<.001). This subgroup showed a significant shift in lipid distribution, mainly, TGs, toward the small, dense LDL subfractions. However, preeclamptic patients in the normal-TG subgroup showed LDL subfraction lipid distribution similar to that of healthy pregnancies. Vascular cell adhesion molecule-1 levels were significantly elevated in preeclamptic patients in comparison with those in control subjects regardless of TG levels. The presence of a proatherogenic lipoprotein profile, previously described in preeclampsia, is characterized by increased small dense LDL and is exclusive to a subset of preeclamptic patients with high TG levels. These findings support the concept of heterogeneous pathogenic lines in preeclampsia and the use of subclassifications in pathophysiologic research on this condition.

Adult↗

A walnut diet improves endothelial function in hypercholesterolemic subjects: a randomized crossover trial.

BACKGROUND: Epidemiological studies suggest that nut intake decreases coronary artery disease (CAD) risk. Nuts have a cholesterol-lowering effect that partly explains this benefit. Endothelial dysfunction is associated with CAD and its risk factors and is reversed by antioxidants and marine n-3 fatty acids. Walnuts are a rich source of both antioxidants and alpha-linolenic acid, a plant n-3 fatty acid. METHODS AND RESULTS: To test the hypothesis that walnut intake will reverse endothelial dysfunction, we randomized in a crossover design 21 hypercholesterolemic men and women to a cholesterol-lowering Mediterranean diet and a diet of similar energy and fat content in which walnuts replaced approximately 32% of the energy from monounsaturated fat. Participants followed each diet for 4 weeks. After each intervention, we obtained fasting blood and performed ultrasound measurements of brachial artery vasomotor function. Eighteen subjects completing the protocol had suitable ultrasound studies. Compared with the Mediterranean diet, the walnut diet improved endothelium-dependent vasodilation and reduced levels of vascular cell adhesion molecule-1 (P<0.05 for both). Endothelium-independent vasodilation and levels of intercellular adhesion molecule-1, C-reactive protein, homocysteine, and oxidation biomarkers were similar after each diet. The walnut diet significantly reduced total cholesterol (-4.4+/-7.4%) and LDL cholesterol (-6.4+/-10.0%) (P<0.05 for both). Cholesterol reductions correlated with increases of both dietary alpha-linolenic acid and LDL gamma-tocopherol content, and changes of endothelium-dependent vasodilation correlated with those of cholesterol-to-HDL ratios (P<0.05 for all). CONCLUSIONS: Substituting walnuts for monounsaturated fat in a Mediterranean diet improves endothelium-dependent vasodilation in hypercholesterolemic subjects. This finding might explain the cardioprotective effect of nut intake beyond cholesterol lowering.

Adult↗

First-trimester screening for trisomy 21 combining biochemistry and ultrasound at individually optimal gestational ages. An interventional study.

OBJECTIVE: To assess the effectiveness of the Combined Test in the prenatal detection of trisomy 21 in the general pregnant population using a new timing for the screening approach. METHODS: First-trimester maternal serum biochemical markers (pregnancy-associated plasma protein-A and free-beta hCG) were determined in maternal serum at 7 to 12 weeks. Fetal nuchal translucency and gestational age were assessed at the 10- to 14-week ultrasound scan. A combined risk was estimated and delivered to the women the same day. When the risk was 1:250 or above, chorionic villus sampling was offered. RESULTS: Mean gestational age at biochemistry was 9.4 weeks, being 12.3 at ultrasound. In the 2780 studied pregnancies with a complete follow-up, observed detection rates were 88% (7/8) for trisomy 21 and 75% (3/4) for trisomy 18, with a 3.3% (92/2765) false-positive rate. CONCLUSION: The Combined Test, assessing biochemistry and ultrasound at individually optimal ages in the first trimester, showed an 88% detection rate for trisomy 21 with a remarkably reduced false-positive rate (3.3%).

Adolescent↗

Rapamycin attenuates atherosclerosis induced by dietary cholesterol in apolipoprotein-deficient mice through a p27 Kip1 -independent pathway.

Activation of immune cells and dysregulated growth and motility of vascular smooth muscle cells contribute to neointimal lesion development during the pathogenesis of vascular obstructive disease. Inhibition of these processes by the immunosuppressant rapamycin is associated with reduced neointimal thickening in the setting of balloon angioplasty and chronic graft vessel disease (CGVD). In this study, we show that rapamycin elicits a marked reduction of aortic atherosclerosis in apolipoprotein E (apoE)-null mice fed a high-fat diet despite sustained hypercholesterolemia. This inhibitory effect of rapamycin coincided with diminished aortic expression of the positive cell cycle regulatory proteins proliferating cell nuclear antigen and cyclin-dependent kinase 2. Moreover, rapamycin prevented the normal upregulation of the proatherogenic monocyte chemoattractant protein-1 (MCP-1, CCL2) seen in the aorta of fat-fed mice. Previous studies have implicated the growth suppressor p27(Kip1) in the antiproliferative and antimigratory activities of rapamycin in vitro. However, our studies with fat-fed mice doubly deficient for p27(Kip1) and apoE disclosed an antiatherogenic effect of rapamycin comparable with that found in apoE-null mice with an intact p27(Kip1) gene. Taken together, these findings extend the therapeutic application of rapamycin from the restenosis and CGVD models to the setting of diet-induced atherosclerosis. Our results suggest that rapamycin-dependent atheroprotection occurs through a p27(Kip1)-independent pathway that involves reduced expression of positive cell cycle regulators and MCP-1 within the arterial wall.

Animals↗

High-density lipoproteins reduce the effect of endotoxin on cytokine production and systemic hemodynamics in cirrhotic rats with ascites.

BACKGROUND/AIMS: Hypersensitivity to endotoxin is a recognized feature in cirrhosis. High-density lipoproteins (HDL) have a high capacity to inactivate endotoxin. The aim was to determine if HDL reduces the effect of endotoxin on cytokine production and systemic hemodynamics in experimental cirrhosis. METHODS: The study was performed in control and rats with carbon-tetrachloride induced cirrhosis with ascites. Hemodynamic parameters were determined before and after several doses of endotoxin. The effects of 25 microg/kg of endotoxin on the serum concentration of TNFalpha and mean arterial pressure (MAP) were determined after treatment with HDL (80 mg/kg) or saline. RESULTS: Whereas endotoxin decreased MAP only at doses of 100 and 1000 microg/kg in control rats, in cirrhotic rats significant hypotension occurred at doses of 25, 50, 100 and 1000 microg/kg. Following the administration of endotoxin (25 microg/kg) the serum levels of TNFalpha were 140 times higher in cirrhotic than in control rats (89?835+/-21?090 vs. 625+/-137 pg/ml; P<0.001). Serum TNFalpha was 80% lower in cirrhotic rats pretreated with HDL (18?890+/-5012 pg/ml; P<0.001) than in those pretreated with saline. The administration of endotoxin (25 microg/kg) was associated with a significant lower decrease of MAP in cirrhotic rats pretreated with HDL than in those receiving saline (11.9+/-3.5 vs. 24.7+/-4.3%; P<0.05). CONCLUSIONS: HDL attenuates the increased effect of endotoxin on cytokine production and systemic hemodynamic in cirrhosis.

Animals↗

Raloxifene inhibits cholesterol aortic content but not atherosclerotic plaque size in oophorectomised cholesterol-fed rabbits.

Raloxifene, a selective oestrogen receptor modulator, is effective in the treatment of osteoporosis without stimulating the breast and the endometrium. Although it is associated with a decrease of cardiovascular risk markers the effect of these changes on atherogenesis, is not clear. In this study, we aimed to investigate the effect of raloxifene on aorta atherogenesis. A total of 32 cholesterol-fed New Zealand white rabbits were studied for 4 months. Twenty-four rabbits underwent bilateral ovariectomy; of these eight received raloxifene (group OR), eight received oestradiol valerate (group OE) and eight received placebo after sterilisation (group OP). Finally, another eight were sham-operated (non-ovariectomised) and received placebo with a hypercholesterolaemic diet (group SP). After the diet, total levels of cholesterol increased in group SP from 111.25 +/- 34.8 mg/dl to 1112.25 +/- 364.2, in group OP from 122.62 +/- 27.7 mg/dl to 1367.37 +/- 348.4, in group OE from 65.25 +/- 17.01 to 1710.5 +/- 356.2 and in group OR from 108.88 +/- 15.54 mg/dl to 1407.86 +/- 397.7 (no significant differences). At 4 months, in both treated and untreated rabbits, the cholesterol-rich diet caused atherosclerotic lesions affecting 24.51 +/- 16.1% for group SP, 30.47 +/- 12.2% for group OP, 30.31 +/- 18.07% for group OR and 17.91 +/- 10.19 for group OE (P<0.05) of the aortic surface, respectively. Aortic cholesterol expressed as mg of cholesterol/mg aortic weight was found to decrease in raloxifene-treated rabbits: 3.82 +/- 2.14 mg col/aortic mg versus 8.55 +/- 4.63 (group OP) and 11.97 +/- 11.33 (group SP). P<0.001. Raloxifene reduced aortic cholesterol content but not the atherosclerotic plaque extension in cholesterol-fed ovariectomised rabbits.

Analysis of Variance↗

Increased susceptibility to low density lipoprotein oxidation in women with a history of pre-eclampsia.

OBJECTIVES: To evaluate the susceptibility to oxidation of low density lipoprotein (LDL) in women with a history of pre-eclampsia. DESIGN: A case-control study. SETTING: The departments of obstetrics and gynaecology at two university teaching hospitals. POPULATION: Women delivering one to three years before enrollment, 35 who were diagnosed with severe pre-eclampsia and 35 controls matched for age, body mass index (BMI), smoking and parity. METHODS: Plasma samples were analysed for total cholesterol, high density lipoprotein (HDL) cholesterol, LDL cholesterol, triglycerides and lipoprotein A. The in vitro susceptibility to oxidation of LDL was measured and expressed in minutes (lag time). Results are expressed as mean and standard deviation. MAIN OUTCOME MEASURES: Serum lipid profile and in vitro susceptibility to oxidation of LDL. RESULTS: Mean LDL cholesterol (116 [37] vs 98 [20] mg/dL, P < 0.05) and trygliceride (112 [56] vs 78 [38] mg/dL, P < 0.05) levels were significantly higher in the groups of women who had pre-eclampsia compared with controls. The rest of the measured lipid parameters were similar between the two study groups. The susceptibility to oxidation of LDL was also significantly higher in the pre-eclampsia group (lag time: 37.9 [8.4] vs 44.8 [9.1] minutes, P < 0.01). CONCLUSION: Women with a history of pre-eclampsia have significant differences in lipid parameters and an increased susceptibility to lipoprotein oxidation when compared with women who had a normal pregnancy one to three years after delivery.

Adult↗

Cyproterone acetate could counteract the benefits of estradiol valerate in oophorectomized cholesterol-fed rabbits.

OBJECTIVE: The administration of hormonal replacement treatment to women with an intact uterus needs to be supplemented with progestogenic compounds to avoid endometrial hyperplasia. However, progestins may cancel the beneficial effects of estrogens on the cardiovascular system. The goal of this study was to examine the effects of adding cyproterone acetate to estradiol (E(2))on aorta atherogenesis. DESIGN: Thirty-two cholesterol-fed New Zealand white rabbits were studied for 4 months. The animals underwent laparotomy and were randomly allocated to four groups. Twenty-four rabbits underwent bilateral ovariectomy, and the other eight were sham-operated (group S). The ovariectomized rabbits were allocated to three groups of eight animals each receiving E(2) valerate (group E), E(2) valerate plus cyproterone acetate (group EC), or placebo after sterilization (group C). RESULTS: After 4 months, the cholesterol-rich diet caused atherosclerotic aortic lesions in both treated groups that affected 17.91% +/- 10.19% and 28.16% +/- 7.97% of the aortic surface of groups E and EC, respectively, with a markedly lower aortic plaque size in group E than in groups C and S. Rabbits from group E (but not from group EC) had aortic cholesterol content significantly lower than rabbits from the sham-operated and control groups. CONCLUSION: E(2) valerate reduces aortic atheromatosis in cholesterol-fed, ovariectomized rabbits, and the addition of cyproterone acetate may neutralize this effect.

Analysis of Variance↗