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R Carmena

Publications and source records attributed to R Carmena.

At least 19 recordsLinked to original sources
PubMed2006

Retinoids induce MMP-9 expression through RARalpha during mammary gland remodeling.

Retinoic acid (RA) is a signaling molecule in the morphogenesis of the mammary gland, modulating the expression of matrix metalloproteinases (MMPs). The aim of this paper was to study the role of RA during weaning, which consists of three events: apoptosis of the secretory cells, degradation of the extracellular matrix, and adipogenesis. CRABP II and CRBP-1 carrier proteins increased significantly during weaning compared with lactating glands but reverted to control values after the litter resuckled. The effects of RA are mediated by the nuclear receptors RARalpha, RARbeta, RARgamma, and RXRalpha, which underwent an increase in protein levels during weaning. In an attempt to elucidate the RARalpha-dependent signaling pathway, ChIP assays were performed. The results showed the binding of RARalpha to the MMP-9 promoter after 24- and 72-h weaning together with its coactivator p300; this fact could be responsible for the increase found in MMP-9 mRNA and protein levels in these conditions. Expression of related MMPs (MMP-2 and MMP-3) was also increased during weaning. Using gelatine zymography, we observed a time-dependent increase in active forms of MMP-9 and MMP-2. On the other hand, the inhibitor of MMPs, TIMP-1, was almost undetectable at 24- and 72-h weaning by Western blot. The role of retinoids in matrix remodeling is reinforced by the fact that administration of an acute dose of retinol palmitate to control lactating rats also induces MMP-9 expression. This emphasizes the importance of retinoids in vivo to regulate mammary gland involution.

Adipogenesis↗
PubMed2006

Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel.

There is abundant evidence that the risk of atherosclerotic vascular disease is directly related to plasma cholesterol levels. Accordingly, all of the national and transnational screening and therapeutic guidelines are based on total or LDL cholesterol. This presumes that cholesterol is the most important lipoprotein-related proatherogenic risk variable. On the contrary, risk appears to be more directly related to the number of circulating atherogenic particles that contact and enter the arterial wall than to the measured concentration of cholesterol in these lipoprotein fractions. Each of the atherogenic lipoprotein particles contains a single molecule of apolipoprotein (apo) B and therefore the concentration of apo B provides a direct measure of the number of circulating atherogenic lipoproteins. Evidence from fundamental, epidemiological and clinical trial studies indicates that apo B is superior to any of the cholesterol indices to recognize those at increased risk of vascular disease and to judge the adequacy of lipid-lowering therapy. On the basis of this evidence, we believe that apo B should be included in all guidelines as an indicator of cardiovascular risk. In addition, the present target adopted by the Canadian guideline groups of an apo B <90 mg dL(-1) in high-risk patients should be reassessed in the light of the new clinical trial results and a new ultra-low target of <80 mg dL(-1) be considered. The evidence also indicates that the apo B/apo A-I ratio is superior to any of the conventional cholesterol ratios in patients without symptomatic vascular disease or diabetes to evaluate the lipoprotein-related risk of vascular disease.

Apolipoproteins B↗
PubMed2006

[Effect of gender and obesity on postprandial lipemia in non-diabetic normolipidemic subjects and subjects with familial combined hyperlipidemia].

INTRODUCTION: A new method based on self-measurement of diurnal capillary triglycerides (TG) facilitates the study of postprandial lipemia (PL). The objectives of our study are: to evaluate the effect of gender and obesity on PL measured by self-determination of diurnal capillary TG with Accutrend GCT in normolipidemic non-diabetic subjects and subjects with familial combined hyperlipidemia (FCH). MATERIAL AND METHODS: We studied 23 FCH subjects (10 males) and 45 normolipidemic non-diabetic subjects (29 males). All subjects self-determine 3 diurnal capillary TG profiles during a week. RESULTS: In normolipidemic non diabetic subjects significantly higher diurnal TG profiles and area under the curve of TG (AUCTGc) (25.25 +/-9.09 vs 19.71 +/- 6.16 mmolh/l) were found in males compared to females. In FCH subjects these differences were not found and the AUCTGc correlated with BMI (r = 0.510, p < 0.05) and waist circumference (r = 0.453, p < 0.05). Obese subjects (BMI >or= 27 kg/m2) showed diurnal TG profiles and AUCTGc significantly higher than the non-obese. DISCUSSION: Normolipidemic non diabetic females showed a lower PL compared to males, probably due to the effect of estrogens in PL metabolism. Obesity negatively influences PL in normolipidemic non diabetic subjects and subjects with FCH.

Adult↗
PubMed2005

Effects of marathon running on plasma total homocysteine concentrations.

AIMS: There is evidence of an excess of acute cardiovascular (CV) events in marathon runners. High plasma total homocysteine (tHcy) concentrations are a recognised risk factor for CV events. Therefore, we investigated the changes in plasma tHcy concentrations 24h before and after a marathon race. METHODS AND RESULTS: Twenty-two non-professional male athletes, mean age 35.6 (6.6), range 23-49 years, were studied the day before and 24 h after finishing a marathon race. None of the athletes was a carrier of the MTHFR 677TT genotype and no ingestion of supplements of vitamins (B12, B6, folic acid) was allowed. RESULTS: Changes in plasma folate and plasma vitamin B12 concentrations were not detected post-race, but a significant increase in plasma tHcy concentrations was demonstrated. Plasma tHcy increased 19% 24h after the race. Before the race 20% of the subjects had a plasma tHcy concentration > 10 micromol/l (cut-off point for ischaemic heart disease risk), while after the race 50% had plasma tHcy concentrations> 10 micromol/l. CONCLUSION: An increase in plasma tHcy concentrations was observed after a marathon race in non-professional not well-trained male athletes performing strong physical activity. The potential physiological or pathological implications of this finding are unknown.

Adult↗
PubMed2005

Role of GSH in the modulation of NOS-2 expression in the weaned mammary gland.

GSH delivery to the lactating mammary gland is essential for the maintenance of lactation as its decrease leads to apoptosis and involution of the mammary gland. In fact, it has already been demonstrated that some of the changes in gene expression found in the lactating mammary gland after forced weaning are reproduced in rats treated with buthionine sulphoximine to deplete GSH levels. An oligonucleotide microarray experiment would give us a better knowledge of the mRNA expression patterns during lactation and after weaning and the possible functions of GSH in the modulation of these events.

Animals↗
PubMed2004

[Plasma lipoprotein (a) values in familial defective ligand apo B 100 in a South European population].

AIMS: 1) to study lipoprotein (a) (Lp(a)) plasma values in subjects with familial ligand-defective apo B 100 (FDB). METHODS: We studied 19 heterozygous FDB subjects (8 males) from 12 families, carriers of R3500Q mutation on apo B gene and 90 controls (34 males). The genetic diagnosis was established with PCR-SSCP analysis and automatic sequencing. In all subjects plasma lipids, apolipoprotein B and Lp(a) levels were determined with standard procedures. RESULTS: Subjects carriers of R3500Q mutation on apo B gene have significantly higher plasma Lp(a) and log transformed Lp(a) values and prevalence of Lp(a) > 30 cut point for coronary heart disease than controls. CONCLUSIONS: Subjects with FDB showed higher Lp(a) plasma values than controls, although the mechanism and the clinical consequences of these result are not known.

Adult↗
PubMed2004

Daylong triglyceridaemia in healthy Mediterranean and northern European subjects.

BACKGROUND: A Mediterranean eating pattern and diet enriched in monounsaturated fatty acids may result in a favourable daylong lipid profile. METHODS: 19 Spanish males (aged 32 +/- 8 years) and 28 females (34 +/- 8 years) were matched to Dutch subjects on the basis of fasting capillary triglycerides (TGc), gender and age. TGc were self-measured at six fixed time points over three days. Daylong TGc profiles were calculated as areas under the curve (TGc-AUC). RESULTS: Anthropometric parameters and fasting plasma lipids were comparable between Spanish participants and Dutch subjects. Insulin sensitivity (expressed as HOMA) was highest in the Dutch females (1.41 +/- 1.09 vs. 2.09 +/- 1.23 in the Spanish females, p < 0.05). Daylong TGc values were not different between Spanish and Dutch participants. Male Spanish subjects showed the largest daylong TGc increase after lunch, while in the Dutch males, the largest TGc increase was seen after dinner. Total daytime dietary energy and total fat intake were comparable when analysed by gender. However, the Spanish participants had a higher intake of monounsaturated and polyunsaturated fatty acids as percentage of energy. CONCLUSION: There are no major differences in daylong triglyceridaemia between Dutch and Spanish subjects, despite different eating habits and a diet enriched in monounsaturated and polyunsaturated fat in the latter.

Adult↗
PubMed2003

Polymorphisms at the SRBI locus are associated with lipoprotein levels in subjects with heterozygous familial hypercholesterolemia.

Scavenger receptor, class B, type 1 (SRBI) is a promising candidate gene involved in the pathophysiology of atherosclerosis. We have examined the association of three common polymorphisms at the SRBI locus in 77 subjects who were heterozygous for familial hypercholesterolemia (FH). The alleles represented by polymorphisms in exon 1 and exon 8 were associated with variation in plasma concentrations of fasting triglyceride (TG). Mean plasma TG concentrations for homozygotes for the most common allele, and for heterozygotes and homozygotes for the less common allele were 85 +/- 6, 111 +/- 9 and 135 +/- 22 mg/dl (p = 0.011) for exon 1, and 96 +/- 11, 86 +/- 6 and 134 +/- 13 mg/dl (p = 0.007) for exon 8, after adjustment for age, sex and body mass index. In addition, the exon 8 polymorphism was associated with increased total cholesterol (320 +/- 15, 340 +/- 8 and 388 +/- 18 mg/dl, p = 0.015), very low density lipoprotein (VLDL) cholesterol (18 +/- 2.9, 15.7 +/- 1.6 and 33.4 +/- 3.9 mg/dl, p < 0.001) and low density lipoprotein (LDL) cholesterol (251 +/- 15, 270 +/- 8 and 312 +/- 10 mg/dl, p = 0.041) concentrations. In agreement with animal studies, our data also suggest a role for the SRBI in the metabolism of apolipoprotein B (apoB)-containing lipoproteins in humans. This pathway may constitute a backup mechanism to LDL receptor-mediated pathways for the catabolism of these lipoproteins, which could be particularly relevant in subjects with high levels of apoB-containing lipoproteins, such as those occurring in patients with FH.

Adult↗
PubMed2001

The influence of apo E phenotypes on the plasma triglycerides response to hormonal replacement therapy during the menopause.

OBJECTIVE: To study the influence of apo E phenotype in plasma lipids, especially in triglycerides levels, in menopausal women receiving hormonal replacement therapy (HRT). METHODS: One hundred and ten postmenopausal women were studied. Plasma total cholesterol (TC), HDL-C and triglycerides (TG) were measured before and after 3 months of HRT and the apo E phenotype was determined. According to the apo E phenotype the sample was divided into three groups: E2/E3 (n=28), E3/E3 (n=96) and E4/E3 (n=25). RESULTS: In the pre-treatment state, higher plasma levels of TC and TC/HDL-C ratio were observed in women with phenotype E3/E4 (P<0.0001 and P<0.02, respectively), while higher plasma TG levels were found in the apo E2/E3 group (P<0.0001). After HRT, women with phenotype E3/E4 showed higher levels of TC and TC/HDL-C ratio (P<0.0001 and P<0.006, respectively). The apo E2/E3 phenotype group showed increased levels of TG (P<0.0001). In the multivariant analysis the changes of TG after HRT were related to the type of treatment used (P<0.001), age (P=0.05) and the apo E phenotype (E2/E3). CONCLUSION: Women with phenotype E2/E3 have higher plasma TG levels and show a significant post HRT increase compared with the other phenotypes. Other factors with a lower impact on TG levels are age and progestagen association.

Administration, Cutaneous↗
PubMed2001

[Risk factors associated to hospitalization in diabetic patients with foot ulcers].

BACKGROUND: To analyse the risk factors associated with admissions of diabetic patients with foot ulcers, in order to prevent hospitalization. In-patient care supposes the greatest cost of the diabetic foot care. SUBJECTS AND METHOD: We studied 108 diabetic patients (male n = 59, mean age 68 [11] years, 100 type 2 diabetics, disease duration 16.4 [10.3]) who attended the diabetic foot unit between January 1996 and September 1997. Clinical and biochemical risk parameters were recorded in a clinical protocol. Patients were followed up for a mean period of 200.2 (121.3) days. Admission was needed for 30 diabetic patients (28%). RESULTS: Risk factors for hospitalization were: higher ulcer diameter (1.9 [1.6] vs 3.4 [2.3] cm, p < 0.05), higher ulceration grade according to Wagner's classification (p = 0.005), presence of > 2 cm cellulitis (p < 0.001), worse metabolic control (HbA1c 7.6 [1.3] vs 8.6 [1.1], p < 0.05), and greater degree of retinopathy (p < 0.005). Odds ratios (OR) for admission were: advanced diabetic retinopathy: OR 1.9 (CI 95% 1.3-2.9; p = 0.02); presence of moderate to severe polyneuropathy: OR 1.6 (CI 95% 1.3-2.1; p = 0.05); upper HbA1c tertile: OR 2.4 (CI 95% 1.2-4.2; p = 0.004). In the logistic regression model, both foot ulcer diameter and advanced diabetic retinopathy were significantly independent. CONCLUSIONS: In diabetic subjects with foot ulcers, hospitalization is independently related to the diameter of the ulcer and the degree of diabetic retinopathy. Therapeutic and preventive approaches should be strengthened in this subgroup of diabetic patients to prevent their hospitalization.

Aged↗
PubMed2001

[Insulin resistance quantification by fasting insulin plasma values and HOMA index in a non-diabetic population].

BACKGROUND: Our goal was to determine the prevalence of insulin resistance (IR) by means of fasting insulin plasma values and the HOMA index,and to analyse the relation of these parameters with other components of the metabolic syndrome. SUBJECTS AND METHOD: We studied 292 non-diabetic individuals, aged between 20 and 65 years, randomly selected from subjects attending an outpatient care center (Valencia-Spain-metropolitan area). 97 subjects who lacked clinical and biological criteria of IR were selected. In addition to calculating the HOMA index, anthropometric parameters, plasma lipids values, fasting glucose and insulin plasma levels were measured by standard methods in all subjects. RESULTS: In the subgroup of 97 subjects without clinical and biological criteria of IR, we established a diagnosis of IR when the fasting plasma insulin value was >= 16.7 mU/l or the HOMA index was >= 3.8. Cut-off points of the percentil 90th of this subgroup were taken into account. In the whole group,the prevalence of IR (HOMA >= 3.8) was 31.8%, with a higher frequency in men compared to women. CONCLUSIONS: In addition to fasting plasma insulin values and HOMA index, the best clinical and biochemical indicators of IR were fasting plasma glucose levels, BMI and triglycerides (TG) plasma values. Thus, the odds ratio for insulin resistance was 5.9 for a glycemia >= 110 mg/dl, 2.6% for BMI >= 25 kg/m(2) and 2.2 for triglycerides >= 150 mg/dl.

Adult↗
PubMed2001

[Influence of FH Valencia 1 and 2 mutations of the LDL receptor gene on the response to simvastatin in subjects with molecularly defined heterozygous familial hypercholesterolemia in Spain].

BACKGROUND: To analyse whether the molecular diagnosis in FH patients is useful to predict the response to treatment with simvastatin in a south European population. SUBJECTS AND METHOD: A randomised clinical trial with no control group, with 20 mg/day of simvastatin was conducted in 27 genetically diagnosed FH subjects (11 male) from 8 FH families, randomly selected from 30 FH families with a molecular diagnosis. Clinical features and lipid parameters at baseline and after simvastatin treatment were compared between subjects classified as null mutations (FH Valencia 1 and 2; n = 11) and defective mutations (n = 16). RESULTS: FH with null mutations (FH Valencia 1 and 2) have a poor response to simvastatin treatment. The mean reduction of plasma LDLc levels in subjects with null mutations were significantly lower (32.6% [9.5] vs 42.8% [12.2]; p = 0.03) than in subjects with defective mutations. Baseline and after treatment plasma HDLc values were also significantly lower in FH group with null mutations. No statistically significant differences were found at baseline, after treatment and in the response to treatment between males and females. CONCLUSIONS: FH subjects with null alleles (FH Valencia 1 and 2) showed a poor response to simvastatin treatment. The type of LDL receptor gene mutation could predict the response to simvastatin in our south European FH population.

Adult↗
PubMed2001

Molecular genetics of familial hypercholesterolemia in Spain: Ten novel LDLR mutations and population analysis.

Mutations underlying FH in Spain are largely unknown because only a few and limited surveys have been carried out on Spanish FH patients up to now. To gain information on this issue, we have analysed a group of 113 unrelated Spanish FH patients from an eastern area of Spain (Valencian Community). We have screened the LDLR gene by Southern blot and PCR-SSCP analysis to detect large rearrangements and small mutations, respectively. In addition, we have screened the Apo B gene for mutations known to cause FDB by PCR-SSCP analysis. We have identified a total of 47 different mutations in the LDLR gene (5 large rearrangements, and 42 small mutations, which were characterized by DNA sequencing), 19 of which have not been described in other populations (Valencia-1 to -4, 112insA, P160R, 790DelATGA, 920insTCAG, G642E, and the ten novel mutations E246A, 884delT, I289T, S305F, Q328X, Y354C, I603del, 2312-3C>A, V779M, and N804K). Three of these mutations (15%) were present in more than 1 proband, being mutation 112insA the most prevalent (frequency approximately 8%) in our sample. The Apo B gene R3500Q mutation was found in only one patient and no underlying defect was found in about 27% of patients. Our data support the notion that Spaniards represent a heterogeneous population with its own spectrum of LDLR gene mutations and that, in our population, FDB has a lower frequency or a milder expression than in central Europe countries.

Apolipoproteins B↗
PubMed2001

Large rearrangements of the LDL receptor gene and lipid profile in a FH Spanish population.

BACKGROUND: Familial hypercholesterolemia (FH) is an autosomal dominant disease caused by mutations in the low-density lipoprotein receptor (LDLR) gene. To date, there has not been a systematic survey of the frequency of gross mutations in the LDLR gene in the Spanish population. The objective of our study was to investigate large rearrangements in the Spanish FH population and the relation between the kind of large rearrangement and the phenotype in carrier families. MATERIALS AND METHODS: The LDLR gene was screened to detect major rearrangements in a sample of 89 probands. Southern blot, long polymerase chain reaction (PCR), reverse transcription (RT) -PCR and DNA sequencing were used to detect and characterize the mutations. RESULTS: Five large rearrangements were found in six probands. Two mutations were due to duplications of internal regions of the gene, whereas the rest were caused by partial deletions, which eliminated the promoter region in two cases. The internal rearrangements, two duplications and one deletion, were apparently caused by recombination between ALU sequences and the study of their mRNA indicated that the reading frame was maintained. The analysis of the lipid profile between patients with similar characteristics (age, sex, body mass index, etc.) but carrying mutations that either eliminated the promoter region or produced internal rearrangements showed significant differences (total cholesterol: 366.6 +/- 81.8 vs. 304.6 +/- 25.1 P = 0.023, and LDL cholesterol: 317.7 +/- 65.1 vs. 249.2 +/- 27.4 P = 0.003). CONCLUSIONS: The frequency of large mutations in a Spanish FH sample was close to 7% and at least four of the mutations found had not been described in other populations. Mutations that eliminate the promoter region originate more severe hypercholesterolemia than defective mutations, which suggests that the absence of the promoter region and transcription of the LDLR gene is worse compensated than the synthesis of a defective LDL receptor.

Adult↗
PubMed2001

Importance of HDL cholesterol levels and the total/ HDL cholesterol ratio as a risk factor for coronary heart disease in molecularly defined heterozygous familial hypercholesterolaemia.

AIMS: To assess the relationship of the lipid profile to coronary heart disease in a group of heterozygous familial hypercholesterolaemic subjects with similar age, sex, body mass index, prevalence of angiotensin converting enzyme DD genotype and type of low density lipoprotein receptor mutation. METHODS AND RESULTS: A total of 66 molecularly defined heterozygous familial hypercholesterolaemic subjects, 33 of whom had coronary heart disease, were studied. Clinical features, cardiovascular risk factors and lipid parameters were compared in both groups. Familial hypercholesterolaemic patients with coronary heart disease showed significantly lower values of mean plasma HDL cholesterol and a higher total/HDL cholesterol ratio as compared with familial hypercholesterolaemic subjects free of coronary heart disease. Total and LDL cholesterol concentrations were higher in patients with coronary heart disease, without reaching statistical significance. No differences in plasma lipoprotein(a) levels on absolute and log-transformed values were observed between the two groups. In the whole familial hypercholesterolaemia group, plasma HDL cholesterol levels were related to plasma triglyceride values and to LDL receptor gene 'null mutations'. CONCLUSIONS: In familial hypercholesterolaemic subjects of similar age, gender, body mass index, systolic and diastolic blood pressure, and genetic factors that could influence coronary heart disease risk, plasma HDL cholesterol values and total/HDL cholesterol ratios are two important coronary risk factors. Hence, treatment of familial hypercholesterolaemia should focus not only on lowering total and LDL cholesterol levels, but also on increasing HDL cholesterol values for coronary heart disease prevention. More prospective and intervention trials should be conducted to establish the relationship of HDL cholesterol levels and coronary heart disease in familial hypercholesterolaemia.

Case-Control Studies↗