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Biomedical subjects

A Miralles

Publications and source records attributed to A Miralles.

At least 19 recordsLinked to original sources
PubMed2006

[Impact of metabolic syndrome on CRP levels].

OBJECTIVE: C-reactive protein (CRP) is considered a marker of subclinical atherosclerosis. The aim of the study was to assess whether the metabolic syndrome (MS) and parameters involved in its diagnosis might influence serum CRP values. PATIENTS AND METHOD: Cross-sectional study in outpatients of a HTA and Vascular Risk clinic. MS was diagnosed according to National Cholesterol Educational Program ATP-III guidelines, and hs-CRP was analyzed by nephelometry. RESULTS: A total of 1,969 patients (47% male) were evaluated and distributed into four groups: 1) 1,220 non-diabetics without MS; 2) 384 non-diabetics with MS; 3) 153 diabetics without MS, and 4) 212 diabetics with MS. Patients with MS had higher CRP in both non-diabetic 3.0 (1.7-4.4) mg/l vs. 1.7 (0.9-3.4) mg/l; p=0.001 (MW), and diabetic patients: 2.8 (1.5-4.6) mg/l vs. 2.2 (0.9-4.3) mg/l; p=0.01 (MW). Diabetic patients without MS had CRP values not different to non-diabetic without MS. CRP values increased in relation to the number of parameters included in the MS from 1.7 (2.2) mg/l, in patients without any parameters, to 4.2 (2.8) mg/l in patients who fulfilled five parameters (p=0.001) (KW). In multiple regression analysis abdominal obesity (p=0.001), TG (p=0.001) and glucose (p=0.02) were associated with CRP levels after correcting for other factors. Abdominal obesity (OR: 1.9; 95% CI: 1.5-2.4; p=0.001) and TG (OR: 1.4; 95% CI: 1.1 -1.7; p=0.003), but not glucose were independent factors related to the presence of high levels of CRP (>3 mg/l) in a logistic regression analysis. CONCLUSIONS: Diabetic and non-diabetic patients with MS have high CRP levels. Of the five components of MS, the most closely related to CRP is abdominal obesity.

Abdomen↗
PubMed2003

Acute myocardial infarction with cardiogenic shock: treatment with mechanical circulatory assistance and heart transplantation.

UNLABELLED: The mortality of cardiogenic shock (CS) after an acute myocardial infarction (AMI) still remains high. Thrombolysis, PTCA or CABG, when possible, can improve the results, but when all the treatments fail death is almost certain. OBJECTIVE: We investigate the use of the mechanical circulatory assistance (MCA) and heart transplantation (HT) to improve the adverse results in this irreversible situation. METHODS: Among 11 patients with irreversible CS after an AMI we used a MCA (Abiomed BVS-5000). After improvement and hemodynamic stabilization, we performed heart transplantation in 7 patients of mean age 52 years (35-60) including two women. The MCA was univentricular in 7 patients and biventricular in 4. Mean duration of the MCA was 5 days (1-12). RESULTS: Three patients died during the MCA: two due to cerebrovascular accidents and one multiorgan failure. Weaning was possible in one patient. Among Seven transplanted patients one died due to sepsis. Seven (64%) patients are long-term survivors. CONCLUSION: When all the treatments have failed for CS after an AMI, MCA may be used as a bridge to heart transplantation in a select group of patients where the procedure is not contraindicated. The long-term results of 64% survivors in our experience is satisfactory.

Adult↗
PubMed2002

Acute treatment with the cyclic antidepressant desipramine, but not fluoxetine, increases membrane-associated G protein-coupled receptor kinases 2/3 in rat brain.

The homologous regulation of receptors is mediated by G protein-coupled receptor kinases (GRKs) which phosphorylate the agonist-activated receptor. This study was designed to assess the in vivo indirect activation of adrenoceptors or 5-HT receptors by the reuptake blocker desipramine or fluoxetine on the cellular distribution of GRK 2/3 in rat brain. Immunoblot analysis (frontal cortex) with a GRK 2 antibody revealed a unique 80 kDa protein (mixed GRK 2/3) in total homogenate (H) and in membrane (P2) and cytosolic (S2) fractions. The proportion of GRK 2/3 in each fraction, relative to that of H, was: P2/H=0.11 and S2/H=0.45. Acute desipramine (noradrenaline reuptake blocker) increased in a dose- (1-30 mg/kg, i.p.) and time- (1-6 h) dependent manner the content of GRK 2/3 in the membrane (P2/H ratios increased by 37-164%). This effect vanished with a prolonged desipramine (30 mg/kg) exposure (24 h). Desipramine did not alter the content of GRK 2/3 in the cytosol (S2/H ratios). Chronic desipramine (10 mg/kg every 24 h) for 14 days did not change significantly the immunodensity of GRK 2/3 in the membrane or the cytosol. The acute administration (2 h) of fluoxetine (5-HT reuptake blocker; 3-30 mg/kg) did not induce significant changes in the content of GRK 2/3 in the membrane (P2/H ratio) or cytosol (S2/H ratio). The results indicate that the in vivo activation of adrenoceptors by desipramine is associated with a time-dependent modulation of membrane-associated GRK 2/3 (i.e. an acute increase in the kinase content which is followed by a return to the basal expression upon repeated treatment). In contrast, the acute in vivo activation of 5-HT receptors induced by fluoxetine does not result in modulation of GRK 2/3.

Animals↗
PubMed2001

The imidazoline receptor ligand 2-(2-benzofuranyl)-2-imidazoline is a dopamine-releasing agent in the rat striatum in vivo.

2-BFI (2-(2-benzofuranyl)-2-imidazoline) is a prototypical I2-imidazoline receptor ligand. In vivo, however, 2-BFI (1-20 mg/kg) decreased the synthesis of dopa/dopamine (DA) in rat striatum through mechanisms not related to interaction with I2-imidazoline receptors or to inhibition of the enzyme monoamine oxidase. The aim of this study was to unravel the mechanism underlying this potent effect of 2-BFI in brain. In vitro 2-BFI showed very low affinity for D2-dopamine receptors (K(i)=47 microM), and in vivo the drug (7 mg/kg) decreased the synthesis of striatal dopa/DA similarly in control rats (43%) and in rats pre-treated with alpha-methyl-para-tyrosine (50%) or cocaine (51%), indicating that this effect was not the result of D2-dopamine autoreceptor direct stimulation, inhibition of the enzyme tyrosine hydroxylase or blockade of neuronal DA reuptake. In DA-depleted (reserpine-treated) rats, however, 2-BFI did not inhibit significantly (11%), the synthesis of dopa/DA in the striatum, indicating that the effect of 2-BFI was indirectly mediated by endogenous DA through the activation of D2-dopamine autoreceptors. In conclusion, the I2-imidazoline receptor ligand 2-BFI is also a DA releasing agent in brain, and consequently a DA indirect agonist in vivo.

Adrenergic Uptake Inhibitors↗
PubMed2001

Synthesis and SAR of a new series of COX-2-selective inhibitors: pyrazolo[1,5-a]pyrimidines.

The synthesis and pharmacological activity of a series of bicyclic pyrazolo[1,5-a]pyrimidines as potent and selective cyclooxygenase-2 (COX-2) inhibitors are described. The new compounds were evaluated both in vitro (COX-1 and COX-2 inhibition in human whole blood) and in vivo (carrageenan-induced paw edema and air-pouch model). Modification of the pyrimidine substituents showed that 6,7-disubstitution provided the best activity and led to the identification of 3-(4-fluorophenyl)-6,7-dimethyl-2-(4-methylsulfonylphenyl)pyrazolo[1,5-a]pyrimidine (10f) as one of the most potent and selective COX-2 inhibitor in this series.

Animals↗
PubMed2001

Brain alpha(2)-adrenoceptors in monoamine-depleted rats: increased receptor density, G coupling proteins, receptor turnover and receptor mRNA.

1. This study was designed to assess the molecular and cellular events involved in the up-regulation (and receptor supersensitivity) of brain alpha(2)-adrenoceptors as a result of chronic depletion of noradrenaline (and other monoamines) by reserpine. 2. Chronic reserpine (0.25 mg kg(-1) s.c., every 48 h for 6 - 14 days) increased significantly the density (B(max) values) of cortical alpha(2)-adrenoceptor agonist sites (34 - 48% for [(3)H]-UK14304, 22 - 32% for [(3)H]-clonidine) but not that of antagonist sites (11 - 18% for [(3)H]-RX821002). Competition of [(3)H]-RX821002 binding by (-)-adrenaline further indicated that chronic reserpine was associated with up-regulation of the high-affinity state of alpha(2)-adrenoceptors. 3. In cortical membranes of reserpine-treated rats (0.25 mg kg(-1) s.c., every 48 h for 20 days), the immunoreactivities of various G proteins (Galphai(1/2), Galphai(3), Galphao and Galphas) were increased (25 - 34%). Because the high-affinity conformation of the alpha(2)-adrenoceptor is most probably related to the complex with Galphai(2) proteins, these results suggested an increase in signal transduction through alpha(2)-adrenoceptors (and other monoamine receptors) induced by chronic reserpine. 4. After alpha(2)-adrenoceptor alkylation, the analysis of receptor recovery (B(max) for [(3)H]-UK14304) indicated that the increased density of cortical alpha(2)-adrenoceptors in reserpine-treated rats was probably due to a higher appearance rate constant of the receptor ((Delta)r=57%) and not to a decreased disappearance rate constant ((Delta)k=7%). 5. Northern- and dot-blot analyses of RNA extracted from the cerebral cortex of saline- and reserpine-treated rats (0.25 mg kg(-1), s.c., every 48 h for 20 days) revealed that reserpine markedly increased the expression of alpha(2a)-adrenoceptor mRNA in the brain (125%). This transcriptional activation of the receptor gene expression appears to be the cellular mechanism by which reserpine induces up-regulation in the density of brain alpha(2)-adrenoceptors.

Adrenergic Uptake Inhibitors↗
PubMed2001

Polymorphism insertion/deletion of the ACE gene and ambulatory blood pressure circadian variability in essential hypertension.

OBJECTIVE: The objective of the present study was to analyze the influence of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme on ambulatory blood pressure values and circadian variability in untreated patients with hypertension. MATERIAL AND METHODS: Ninety-nine essential hypertensive patients, less than 50 years old (mean age 39.5+/-7.0 years), previously untreated with antihypertensive drugs were included. Twenty-four hour ambulatory blood pressure monitoring (ABPM) was performed with a Spacelabs (90202 and 90207) monitor, during a regular working day in unrestricted ambulatory conditions. The I/D polymorphism of the ACE was determined by PCR. RESULTS: The distributions of genotypes were in Hardy-Weinberg equilibrium: I=17 (17%), ID=41 (41.5%), DD=41 (41.5%). No significant differences were present among the groups in terms of age, sex, and biochemical and lipid profiles. The average of 24-h ambulatory blood pressure was slightly higher in patients with the DD genotype as compared with patients with the II and ID genotypes. This was the result of higher nighttime blood pressure values, because no differences in blood pressure were observed during daytime. The systolic blood pressure (SBP) day:night ratio, as an estimate of circadian variability, was significantly lower in subjects homozygous for the D allele than it was in patients carrying the I allele (1.13+/-0.09 vs. 1.17+/-0.08, P=0.014). The subjects in the lowest tertile of the SBP day:night ratio, exhibited a higher frequency of the D allele when compared with those in the middle tertile (0.74 vs. 0.59, P<0.05) or with those in the highest tertile (0.74 vs. 0.54, P<0.01). By using two-way ANOVA with repeated measures, significant differences in SBP variation over time were observed when comparing homozygous for the D allele with subjects carrying the I allele (F=2.11, P=0.002). CONCLUSIONS: Among the genotypes of the I/D polymorphism, subjects carrying DD genotype showed a blunted decline of the physiological nocturnal fall of blood pressure that was significant for SBP.

Adult↗
PubMed2001

Long-term ovarian function evaluation after autografting by implantation with fresh and frozen-thawed human ovarian tissue.

The transplantation of ovarian tissue has recently been the focus of intense investigation with the aim of avoiding premature ovarian failure mainly in patients receiving chemotherapy or radiotherapy for malignant disease. Here, we present an evaluation of the long-term function of both fresh (patients 1, 2, and 3) and cryopreserved (patient 4) ovarian autografts in four premenopausal patients aged 46-49 yr who underwent heterotopic ovarian transplantation and were followed over a 1-yr period without receiving gonadotropins to stimulate follicular growth. In patients 1 and 2, approximately 1 cm(3) ovarian cortical autograft was placed sc in the inner aspect of the arm, whereas and in patients 3 and 4 minced ovarian tissue was placed into a muscle pocket in the abdominal wall. In patients 1, 2, and 4 the ovarian hormone secretion (as suggested by sequential estradiol and FSH serum measurements) was reestablished 3-4 months after autotransplantation, and graft function was not improved by immediate rather than delayed heterotopic ovarian autografting. Despite a reestablished ovarian function, a 2- to 7-fold increase in peripheral FSH concentration was evidenced. The cases reported here suggest that hormonal protection can be restored after fresh or cryopreserved heterotopic ovarian transplantation in women, albeit for only a short reproductive span.

Chorionic Gonadotropin↗
PubMed2000

[Factors associated with changes in microalbuminuria during antihypertensive treatment].

BACKGROUND: The objective of the present study was to analyze the factors related with changes of microalbuminuria during antihypertensive treatment in patients with essential hypertension. METHODS: One hundred and six patients (57 men, mean age 40.8 [SD 6.6] years) never treated with antihypertensive treatment were included. At the beginning and after one year, blood pressure biochemical profile and urinary albumin excretion (UAE) were measured. After the initial evaluation, 53 patients received angiotensin converting enzyme inhibitors (ACEi) and 53 beta-blockers (BB). Hydrochlorothiazide was added to achieve the blood pressure target < 140/90 mmHg. RESULTS: The average of UAE was 32.1 (43.1) mg/24 h, and 41 (39%) patients had microalbuminuretics. After 12 months of treatment, a significative fall of systolic BP (-20.6 [8.03] mmHg, p < 0.001), and diastolic BP (-14.18 [10.34] mmHg, p < 0.001) were observed, whereas baseline glucose increases (3.08 [11.07] mg/dl, p = 0.006). The changes of UAE were only related with the baseline UAE values. Neither, age, sex, baseline diastolic BP and changes in diastolic BP were significantly related with the changes in UAE. In spite of similar mean BP reduction (medial BP 17.4 [10.9] vs 14.8 [10.4] mmHg), UAE only was reduced in patients treated with ACEi (LogUAE: 0.203 [0.872] mg/24 h; p < 0.04). In addition, in patients treated with BB a significative increase in baseline glucose (4.4 [12.3] mg/dl; p = 0.013) and uric acid (1.18 [4.18]; p = 0.031) were observed. CONCLUSIONS: In patients with essential hypertension, changes in microalbuminuria depends of the initial UAE values and the kind of antihypertensive treatment. ACEi produced higher UAE reduction and lower derangement of the glucose metabolism than BB.

Adrenergic beta-Antagonists↗
PubMed2000

Optimization of a method for the cryopreservation of rabbit corneas: attempted application to human corneas.

The purpose of the present study was to set up and test a cryopreservation method for long-term storage of human corneas. Therefore the freezing solution was optimized in 264 rabbit corneas by testing the type of cryoprotectant, its concentration, addition and dilution pattern and exposure temperature. Then rabbit corneas were frozen in the optimum solution at different cooling rates and thawed in a water bath at different temperatures. Eight human corneas were cryopreserved with the method showing optimum results in rabbit corneas and four additional corneas were used as controls. Endothelial viability was assessed after each step by vital staining and scanning electron microscopy. Best results after exposure of rabbit corneas to the freezing solution were achieved when using a 10% cryoprotectant concentration, with direct addition/dilution and exposure at room temperature (3512 +/-300 viable cells mm(2) when using dimethylsulfoxide; 3403 +/- 245 viable cells mm(2) when using 1,2-propanediol). Cryopreserved rabbit corneas had the highest endothelial cell survival when frozen at 1 degrees C/min and thawed at 37 degrees C (2003 +/- 372 viable cells/mm(2) when using dimethylsulfoxide and 1357 +/- 667 viable cells/mm(2) when using 1,2-propanediol). Cryopreserved human corneas had 753 +/- 542 viable cells/mm(2) when using dimethylsulfoxide and 56 +/- 56 viable cells/mm(2) when using 1,2-propanediol. We can conclude that the method developed is easy to handle and shows optimum results in rabbit corneas, with an endothelial cell survival that is consistent with transplant acceptability criteria. The results obtained in human corneas are below prediction and are still unsatisfactory for successful use in eye banking.

Journal Article↗
PubMed2000

Chronic clorgyline induces selective down-regulation of alpha2-adrenoceptor agonist binding sites in rat brain.

Inactivation of alpha2-adrenoceptors by N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) has been shown to induce an increase in brain regulatory G alpha(i1/2) proteins, which was related to biphasic recovery of agonist binding sites. To investigate further the nature of this phenomenon, the chronic effects of clorgyline (a monoamine oxidase inhibitor antidepressant) on the recovery of alpha2-adrenoceptors after EEDQ and on EEDQ-induced up-regulation of G alpha(i1/2) proteins were assessed in rat brain. Clorgyline (1 mg kg(-1) for 7-35 days) induced a time-dependent down-regulation (20% to 55%) of the density of cortical alpha2-adrenoceptor agonist sites ([3H]UK 14304/bromoxidine binding) but not of antagonist sites ([3H]RX 821002/2-methoxy idazoxan binding). However, chronic clorgyline did not alter the immunoreactive levels of G alpha(i1/2), G alpha(i3), and G alpha(o) proteins in cortex. In clorgyline-treated rats, the turnover functions for agonist and antagonist binding sites (receptor recovery after EEDQ) were different and indicated that the reduced density of alpha2-adrenoceptor agonist sites induced by clorgyline was due to a greater rate of receptor disappearance. The recovery of [3H]UK 14304 binding in clorgyline-treated rats did not fit a biphasic recovery model and the turnover parameters were very similar to those obtained for the second phase of recovery (biphasic model) of agonist binding sites in naive rats. This suggested that clorgyline down-regulated only the alpha2-adrenoceptors of rapid turnover which is associated with the increases in the expression of G alpha(i1/2) proteins induced by EEDQ. In this context, clorgyline (1 mg kg(-1) for 7 days) fully prevented the up-regulation (50%) of brain G alpha(i1/2) proteins induced by EEDQ. The results indicate that one relevant mechanism involved in the in vivo desensitization of brain alpha2-adrenoceptors is an effective impairment of receptor-G protein coupling.

Adrenergic alpha-Agonists↗
PubMed1999

Effects of anti-sense oligonucleotides directed toward dihydrofolate reductase RNA in mammalian cultured cells.

The effect of incubations with anti-sense phosphorothioate oligonucleotides directed toward sequences of dihydrofolate reductase (DHFR) RNA has been tested on Chinese hamster ovary cells. The selected targets were the 5'-untranslated region, the translational start, the splice sites and branch point of intron I and polyadenylation regions 1 and 3 of the DHFR RNA. To introduce the oligonucleotides, the cationic liposome DOTAP was used. The oligonucleotides most effective at causing cytotoxicity were ATNL and DTNL, both directed toward the translation-start site, at a range of concentrations between 1 and 4 microM. The minimum time for the oligonucleotide to exert its full cytotoxic effect was 3 days. Excess of oligonucleotide diminished the cytotoxic effect. Oligonucleotide uptake was monitored by the incorporation of [32P]- or fluorescein-labeled oligonucleotide and was found to depend on liposome and oligonucleotide concentrations and duration of incubation. Formation of in vitro complexes between the oligonucleotide and the liposome was also studied. Cytotoxicity was observed when the oligonucleotide was incubated with cell lines containing either the endogenous gene or co-transfected DHFR minigenes. Cell incubation with ATNL caused a time-dependent decrease in the levels of DHFR mRNA and enzymatic activity. Moreover, a cell line bearing amplification at the dhfr locus was equally affected by the action of ATNL. Human hepatoma cells were also affected by treatment with the counterpart of ATNL in the human DHFR mRNA sequence. Our results set the basis for a possible cancer therapy with anti-sense oligonucleotides using DHFR as the target.

Animals↗
PubMed1999

[Insertion/deletion polymorphism of the gene encoding for angiotensin-converting enzyme and microalbuminuria in essential arterial hypertension].

BACKGROUND: To assess the influence of insertion/deletion polymorphism in the ACE gene on the microalbuminuria in essential hypertension. PATIENTS AND METHODS: Seventy-nine patients with essential hypertension (37 males and 42 females) (mean age 39 [7] years, body mass index 28 [4] kg/m2), never treated with antihypertensive drugs were included in the study. Urinary albumin excretion (UAE) was assessed in two different days. Ambulatory blood pressure (BP) was assessed during 24 h period. Genotype ACE gene and gene frequencies were determined by an assay based on the polymerase chain reaction (PCR). RESULTS: The distribution of phenotypes was: II = 14 (17%), ID = 32 (40%) and DD = 33 (43%). The mean for UAE tended to be higher in the DD group (53.82 [88.4] mg/24 h) than ID (27.8 [39.6] mg/24 h) and II (23.8 [16.7] mg/24 h). Likewise, the average for UAE were higher in the DD group than in the II + ID group (26.6 [34.0] mg/24 h) (p = 0.06), although the differences did not achieved statistical significance. The relationship between log UAE and 24-hour mean BP was significantly higher in the DD group (r2 = 0.232; p = 0.005) than that observed in the other groups (r2 = 0.060; p = 0.101). CONCLUSIONS: In the present study with young patients with essential hypertension, in DD genotype, UAE seems to be higher and more dependent of BP levels than in the other hypertensives.

Adult↗