Biomedical subjects

Carmen Domínguez

Publications and source records attributed to Carmen Domínguez.

8 recordsLinked to original sources

PubMed2006

Placental angiogenic growth factors and uterine artery Doppler findings for characterization of different subsets in preeclampsia and in isolated intrauterine growth restriction.

OBJECTIVE: The purpose of this study was to evaluate possible relationships between placental markers and endothelial dysfunction in preeclampsia and intrauterine growth restriction. STUDY DESIGN: A prospective study was conducted in 76 patients with preeclampsia and 37 patients with intrauterine growth restriction that were classified as early onset (<34 weeks of gestational age) or late onset, and 40 control subjects. Plasma levels of placental growth factor, soluble fms-like tyrosine kinase-1, vascular cell adhesion molecule-1, and uterine artery Doppler indices were measured. RESULTS: In early-onset preeclampsia and intrauterine growth restriction, placental growth factor was lower and soluble fms-like tyrosine kinase-1 and vascular cell adhesion molecule-1 higher than in control subjects, although all changes were more pronounced in preeclampsia. In late-onset preeclampsia, those patients with abnormal uterine artery Doppler indices had higher soluble fms-like tyrosine kinase-1 and vascular cell adhesion molecule-1 levels. CONCLUSION: Biochemical changes in early-onset preeclampsia and intrauterine growth restriction point to a common placental disorder and a state of endothelial dysfunction, which may require interaction with other factors to explain the maternal disease in preeclampsia. Data in late-onset preeclampsia suggest that a proportion of them may occur with minimal placental involvement.

Adult↗

PubMed2005

Dipeptides as effective prodrugs of the unnatural amino acid (+)-2-aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (LY354740), a selective group II metabotropic glutamate receptor agonist.

(+)-2-Aminobicyclo[3.1.0]hexane-2,6-dicarboxylic acid (1), also known as LY354740, is a highly potent and selective agonist for group II metabotropic glutamate receptors (mGlu receptors 2 and 3) tested in clinical trials. It has been shown to block anxiety in the fear-potentiated startle model. Its relatively low bioavailability in different animal species drove the need for an effective prodrug form that would produce a therapeutic response at lower doses for the treatment of anxiety disorders. We have investigated the increase of intestinal absorption of this compound by targeting the human peptide transporter hPepT1 for active transport of di- and tripeptides derived from 1. We have found that oral administration of an N dipeptide derivative of 1 (12a) in rats shows up to an 8-fold increase in drug absorption and a 300-fold increase in potency in the fear-potentiated startle model in rats when compared with the parent drug 1.

Administration, Oral↗

PubMed2005

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↗

PubMed2005

Estimation of lipoperoxidative damage and antioxidant status in diabetic children: relationship with individual antioxidants.

Increased oxidative stress has emerged as a potential mechanism implicated in the pathogenesis, progression and cell dysfunction associated with many diseases including diabetes. In routine clinical practice, the estimation of the degree of oxidative damage and antioxidant status, even in paediatric patients, by appropriate techniques appears to be of interest. The aim of this study was to reliably identify patients with increased oxidant stress and/or reduced antioxidant defence mechanisms with a small blood sample and verify the applicability to the study of diabetic children (DC) at clinical onset of the disease. In 1-ml blood samples from 30 DC and 34 controls, techniques for accurately measuring malondialdehyde (MDA) concentrations in plasma and erythrocytes (using HPLC analysis with fluorometric detection), total radical antioxidant potential (TRAP) and blood plasma oxidizability were adapted and validated. Plasma alpha-tocopherol (HPLC), uric acid and sulfhydryl (SH) groups were also determined. At clinical onset of diabetes a significant reduction in plasma TRAP values (P<0.01) was observed in DC compared with controls. Similarly, a significant fall in individual antioxidant levels (alpha-tocopherol/total lipids, uric acid and protein SH) was noted in plasma of DC. Highly significant increases were found in both plasma and erythrocyte MDA levels in DC (p-MDA:1.7+/-0.2 microM; er-MDA: 7.2+/-0.7 nmol/g Hb) compared with controls (p-MDA:0.86+/-0.09 microM; P<0.0003; er-MDA:3.8+/-0.2 nmol/g Hb, P<0.0001). Plasma MDA and triglyceride levels correlated directly only in DC (P<0.001). Whole plasma oxidizability was significantly higher in DC than in controls (P<0.0001) and this parameter correlated significantly with plasma cholesterol and triglyceride concentrations (P<0.0001). The micromethods adapted and applied to the simultaneous detection of lipid peroxidation products and antioxidant status permit accurate and reliable assessment of the oxidative stress process in small plasma samples. Our results clearly show systemic peroxidative damage associated with insufficient defence mechanisms against ROS to be already present at clinical onset of type 1 diabetes mellitus in children and adolescents.

Adolescent↗

PubMed2004

Nitric oxide protects against pancreatic subcellular damage in acute pancreatitis.

OBJECTIVES: Oxidative stress involvement in damage to the pancreas in acute pancreatitis (AP) is well documented. However, little is known about oxidative damage occurring in the different subcellular fractions of pancreatic cells. The aim of this study was to ascertain the main targets of oxidative damage inside cells after AP and the role of endogenous nitric oxide (NO) in it. METHODS: A model of cerulein-induced AP in rats was used and N-nitro-l-arginine methyl ester (l-NAME) was administered as an NO production inhibitor. After pancreatitis induction, indicative parameters of lipid peroxidation and protein oxidation together with some enzymatic and nonenzymatic endogenous free radical scavengers were assessed in serum and pancreatic subcellular fractions. CONCLUSIONS: In pancreatitic rats, malondialdehyde and protein carbonyl group concentrations were significantly increased (P < 0.05) in serum and some fractions. The increases were higher in l-NAME-treated rats (P < 0.05). Superoxide dismutase and catalase activities were also increased (P < 0.05) but were decreased (P < 0.05) with l-NAME. The alpha-tocopherol concentration diminished (P < 0.05) in serum and all the studied subcellular fractions and the decrease was stronger in l-NAME-treated rats. Our data suggest that microsomes followed by lysosomal + mitochondrial are the fractions most susceptible to oxidative damage in AP. Endogenous NO plays a protective role against oxidative damage to subcellular fractions.

Acute Disease↗

PubMed2003

Biomarkers of diabetes-associated oxidative stress and antioxidant status in young diabetic patients with or without subclinical complications.

The aims of the study were to ascertain the potential role of oxidative stress in the onset of disease-related pathophysiological complications in young type 1 diabetes patients. Indicative parameters of lipoperoxidation, protein oxidation, and changes in antioxidant defense system status were measured in blood samples from 26 young diabetic patients with recently diagnosed (< 6 months) microangiopathy (+DC), 28 diabetic patients without complications (-DC), and 40 healthy age-matched controls (CR). Both diabetic groups presented similar fructosamine and glycated hemoglobin (HbA1c) values. Results showed erythrocyte glutathione peroxidase activity, glutathione content, and plasma beta-carotene to be significantly lower in diabetic patients compared with control subjects, but with no significant differences between -DC and +DC groups. Antioxidant enzyme superoxide dismutase activity was significantly higher in the erythrocytes of diabetic patients independently of the presence of microvascular complications. However, the plasma alpha-tocopherol/total lipids ratio was significantly diminished in +DC group compared with -DC (p =.008). Lipid peroxidation indices measured in plasma included malondialdehyde, lipid hydroperoxides, and lipoperoxides, which were significantly elevated in our diabetic patients regardless of the presence of complications. Evidence of oxidative damage to proteins was shown both through the quantification of plasma protein carbonyl levels, which were significantly higher in -DC (0.61 +/- 0.09 mmol/mg prot), and higher still in the +DC patients (0.75 +/- 0.09 mmol/mg prot) compared with those of controls (0.32 +/- 0.03 mmol/mg prot; p <.01) and immunoblot analysis of protein-bound carbonyls. Additionally, a marked increase in protein oxidation was observed in +DC patients through assessment of advanced oxidation protein products (AOPP) considered to be an oxidized albumin index; AOPP values were significantly higher in +DC than in -DC patients (p <.01) and CR (p <.0001). These results point to oxidatively modified proteins as a differential factor possibly related to the pathogenesis of diabetic complications.

Adolescent↗

PubMed2002

Aluminum ions induce DNA synthesis but not cell proliferation in human fibroblasts in vitro.

The effect in vitro of aluminum (Al) ions on DNA synthesis and human dermal fibroblast proliferation using [Al] concentrations from 1.85 to 74 microM and incubation periods of 1, 2, 3, 4, and 5 d was assessed. The lowest concentration of Al that exerted a slight positive, although not significant, effect on DNA synthesis was 1.85 microM, after d 3 or 5 of incubation. The stimulating action of Al was more evident and statistically significant from concentrations of 3.7 microM and 2 d exposure onward. This Al-induced effect on [3H] thymidine incorporation into DNA increased in a time-dependent manner as [Al] in the culture medium rose, provoking increments of up to 322% above the control at [Al] 74 microM and 5 d incubation. In contrast, Al salts moderately increased fibroblast division in a continuous manner only from 7.4 to 74 microM after 3 d of incubation. Although significant overall, the minimal and inconstant mitogenic activity of Al differs greatly from and is not parallel to DNA synthesis, which is not clearly related to exposure times or Al concentrations. Abnormalities in Al-induced cellular metabolic processes described herein and their influence on the cell cycle may constitute a toxicity mechanism for human tissues, leading to disease development. Further studies are required to determine whether these findings can be extrapolated to in vivo situations.

Adolescent↗

PubMedDate not supplied

Comparative characterization of a wool-wax extract by two complementary chromatographic techniques.

A detailed characterization of lipids present in a wool-wax extract, obtained by supercritical fluid extraction, is presented. Thin-layer chromatography coupled to a flame ionization detector (TLC-FID) has been used as a screening technique to identify the different chemical classes of complex mixtures. Furthermore, to confirm peak identification obtained by TLC-FID and to check its suitability as a quality control technique, preparative TLC fractionation has been carried out by re-analyzing the different fractions obtained by TLC-FID and by gas chromatography coupled to mass spectrometry in the electron impact and in the chemical ionization modes. By means of this comparative study, the TLC-FID identification has been confirmed. Also, the complementarity of the different techniques used confirmed the identification of different lipid classes, namely fatty acids, alcohols, sterols, sterane diol, stanone, steryl sulphate, hydroxyacids, alkane diols, aliphatic and steryl esters, hydroxy steryl esters, triacylglycerol, diesters, and ceramides types II and VI.

Animals↗