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Biomedical subjects

R Alonso

Publications and source records attributed to R Alonso.

At least 37 records · Page 2Linked to original sources

Sustained long-term improvement of arterial endothelial function in heterozygous familial hypercholesterolemia patients treated with simvastatin.

Patients with heterozygous familial hypercholesterolemia (hFH) are at very high risk for premature coronary heart disease. In the last decade, treatment with statins has reduced cardiovascular mortality in these patients. The aim of this study was to analyze arterial endothelial function assessed as flow-mediated dilatation (FMD) and soluble E-selectin (sE-selectin) levels in patients with hFH under a long-term lipid-lowering treatment. Twenty-five patients who completed the study received a dose of simvastatin to achieve a treatment goal of at least 30% reduction in serum low-density lipoprotein (LDL)-cholesterol (LDL-C) for 52 weeks. Functional and biochemical measurements were taken at entry, and at week 12 and 52 of treatment. FMD was measured by vascular ultrasound of the brachial artery. sE-selectin, tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 were determined by enzyme linked immunosorbent assay (ELISA). LDL-C levels were significantly reduced by treatment at week 12 and maintained at week 52 (reduction vs. baseline, 44+/-12 and 43+/-11%, respectively, P<0.0001). A significant improvement in endothelial function, measured as FMD (baseline, 4.7+/-6.2%; 12 weeks, 12.3+/-5.9%; 52 weeks, 9.7+/-4.7%; P<0.005) and a reduction in sE-selectin levels (baseline, 16.2+/-3.4 ng/ml; 12 weeks, 11.0+/-3.2 ng/ml; 52 weeks, 12.3+/-4.2 ng/ml; P<0.01) were observed. Endothelial-independent relaxation induced by nitroglycerin was not modified during the study. Our results indicate that a long-term treatment with simvastatin produced a sustained beneficial effect in endothelial function in hFH patients.

Adult↗

[Aeromonas spp bacteremia: study of 12 cases and review of the literature].

Twelve cases of Aeromonas spp. bacteremia are here reviewed in adult patients occurred at our institution during a 6-year period. Three cases corresponded to patients with hematological disease and four had a solid neoplasm. The source of infection in seven patients was extra-nosocomial; infections in the five remaining patients were considered to be acquired in the hospital. In seven patients, potential portals of entry were found. The usual clinical presentation was febrile syndrome in all cases and only in two patients did the clinical picture evolve to fulminant septic shock. Speciation of microorganisms was determined in only four cases: 2 A. hydrophilia, 1 A. caviae, and 1 A. veronii. Most isolates were susceptible to aminoglycosides, cotrimozazol, phosphomycin, and quinolonos, and resistant to ampicillin. Three patients (25%) died as a result of the infection. Aeromonas spp. bacteremia represented 0.12% of blood cultures in our hospital and occurs in immunosuppressed patients although it may be reported in previously healthy individuals.

Adult↗

Thermal treatment improves nutritional quality of pea seeds (Pisum sativum L.) without reducing their hypocholesterolemic properties.

The effects of isoproteic isoenergetic diets containing raw (RP) or extruded (EP) pea (Pisum sativum, cv. Ballet) seed meal on nutritional performance and serum lipids, amino acids and enzyme levels in growing rats were studied in two 15 d feeding experiments. Food intake and growth were greatly reduced in animals fed unsupplemented RP or EP. Both parameters were improved by addition of amino acids to the diets. Growth, apparent N digestibility, biological value and net protein utilisation values for supplemented (SRP) raw peas were however inferior to those for controls whilst with supplemented (SEP) extruded peas the values were similar to control levels. SRP and SEP also greatly reduced serum total cholesterol, LDL (VLDL) and cholesterol/HDL ratio. This may have been linked to the lower plasma lysine:arginine ratio. SRP and SEP increased kidney and adrenal weights and reduced liver weight. SRP stimulate pancreatic growth but SEP did not. Analysis of serum proteins and enzymes suggested these tissue changes did not lead to chronic disruption to gut or systemic metabolism. Extrusion treatment of peas improved their nutritional quality but did not reduce their hypocholesterolemic properties.

Journal Article↗

Sex steroids modulate luteinizing hormone-releasing hormone secretion in a cholinergic cell line from the basal forebrain.

The function of a particular neuronal population is in part determined by its neurotransmitter phenotype. We have found that a neuronal-derived septal cell line (SN56), known for its cholinergic properties, also synthesizes and releases luteinizing hormone-releasing hormone. In addition, these cells express the messenger RNAs encoding estrogen and progesterone receptors. The activation of these receptors by their respective ligands cooperatively modulates the depolarization-induced release of luteinizing hormone-releasing hormone in these cells. We have also found that a number of septal neurons in postnatal (1-week-old) mice are immunoreactive to both choline acetyltransferase and luteinizing hormone-releasing hormone. These results indicate that both neurotransmitters, acetylcholine and luteinizing hormone-releasing hormone, may co-exist in septal neurons of the CNS and that they could be modulated by gonadal hormones, and suggest that luteinizing hormone-releasing hormone could be involved in some of the actions of sex steroids on cholinergic neurotransmission.

Animals↗

The amount of estrogen receptor alpha increases after heat shock in a cholinergic cell line from the basal forebrain.

Estrogen exerts a neuroprotective action in response to a variety of cell stresses. However, to what extent intracellular estrogen receptors are involved in these functions remains to be determined. We have found that SN56 cells, a neuronal-derived cholinergic cell line which produces luteinizing hormone-releasing hormone and contains the mRNAs encoding estrogen and progesterone receptors, also express estrogen receptor alpha, as well as the heat shock protein 90. Exposure of these cells to drastic temperature elevation for 1 h immediately increased the intracellular levels of these two proteins, whereas it rapidly reduced the content of estrogen receptor alpha mRNA. In addition, the amount of estrogen receptor alpha-heat shock protein 90 complexes was increased in response to thermal stress. Pre-treatment with geldanamycin, a potent inhibitor of heat shock protein 90, decreased the amount of estrogen receptor alpha, suggesting that its elevation after the heat insult may be related to its association with heat shock protein 90. In contrast, exposure of heat-shocked cells to 17beta-estradiol reduced the number of estrogen receptor alpha-heat shock protein 90 complexes, suggesting that the receptor conserves the affinity for its cognate ligand under these conditions. Therefore, the interaction of the estrogen receptor with heat shock protein 90 may serve to prevent its degradation during the thermal insult, as well as to maintain it in a high-affinity hormone-binding conformation. Since neuroprotective estrogen effects have been described in a variety of cytotoxic situations, these findings may be suggestive of an integrated neuronal response to injury, which includes the protection of available estrogen receptors through their association with heat shock protein 90.

Benzoquinones↗

Dissolution of salts crystallised in building materials using ultrasound: an alternative to NORMAL (1983) standard methodology.

Our aim in the present work is to extract salts from ornamental stone using a faster and less tedious method than the customarily used NORMAL method [NORMAL, Dosaggio dei Sali Solubili, CNR-ICR, Roma, Italy (1983) 13/83]. For extraction in aqueous medium, the latter method requires shaking for 72 h at a temperature of 60 degrees C. Our aim is to attempt to shorten this time to less than 1 h using ultrasound. The results of the present study indicate that there is a good correlation between the amount of salts extracted applying the method described in the NORMAL (1983) normative and the amounts extracted with the method proposed here, subjecting the material to ultrasound (50 KHz) for 45 min.

Journal Article↗

Molecular analysis of relapse vs re-infection in HIV-positive patients suffering from recurrent Clostridium difficile associated diarrhoea.

Recurrence is a major complication of Clostridium difficile associated diarrhoea, especially in human immunodeficiency virus (HIV) positive patients, and it is important to distinguish between relapse and re-infection in recurrent episodes. The aim of our study was to analyse C. difficile isolates obtained from HIV-positive patients with recurrent diarrhoea in order to distinguish between relapse and re-infection. This analysis was based on the study of DNA similarities among isolates obtained from different episodes within each patient. Relapses occurred in 64% of patients, 32% suffered re-infections and a combination of relapse plus re-infection was seen in 4%. DNA typing methods can be useful tools to characterize recurrent episodes of C. difficile associated disease.

AIDS-Related Opportunistic Infections↗

"Second-look" cytotoxicity: an evaluation of culture plus cytotoxin assay of Clostridium difficile isolates in the laboratory diagnosis of CDAD.

Clostridium difficile is one of the most frequent causes of hospital-acquired diarrhoea. Our objective was to prove that some stool samples with a direct negative cytotoxicity assay may indeed harbour toxigenic C. difficile and that this can be demonstrated by performing a "second-look" cytotoxicity assay using the isolated C. difficile strains. Over an eight-year period (1992-1999), the 8241 stool samples submitted for direct cell culture from patients with suspected C. difficile-associated diarrhoea (CDAD) were simultaneously plated on cycloserine cefoxitin fructose agar. C. difficile strains isolated from samples with a negative direct cell culture assay were re-tested for toxin production "second-look" cell culture assay). Using both methods 6423 samples (78%) were negative. Of the remaining 1818 samples, 127 (7%) yielded C. difficile isolates which were confirmed as non-producers of toxin by both methods, 1437 (85%) were positive in direct cell culture assay, and 254 were positive only after the "second-look" cell culture assay. Thus, our approach allowed us to detect an extra 15% of toxin-producing strains that could have gone undetected otherwise.The combination of direct-cell culture assay, culture for toxigenic C. difficile and "second-look" cell culture assay enhances the potential for diagnosis of CDAD and enables us to be more efficient with our patient care resources.

Bacterial Toxins↗

In vitro activity of new quinolones against Clostridium difficile.

We evaluated the in vitro activities of ofloxacin, levofloxacin, grepafloxacin, trovafloxacin and ciprofloxacin against Clostridium difficile. The MIC(90) was 128 mg/L for ofloxacin and levofloxacin, 64 mg/L for ciprofloxacin, 16 mg/L for grepafloxacin and 8 mg/L for trovafloxacin. Thirty per cent of isolates were resistant to trovafloxacin, and rates of resistance to ofloxacin, levofloxacin, grepafloxacin and ciprofloxacin were considerably higher. None of the antimicrobials studied would be a reliable therapeutic option against C. difficile. Whether some of the new fluoroquinolones can induce C. difficile-associated diarrhoea remains to be answered.

4-Quinolones↗

Estrogen modulates alpha(1)/beta-adrenoceptor- induced signaling and melatonin production in female rat pinealocytes.

Nocturnal rise in pineal melatonin output is due to the night-induced acceleration of noradrenergic transmission and alpha(1)- and beta-adrenoceptor activation. In addition, in female animals, cyclic oscillations in circulating levels of sex steroid hormones are accompanied by changes in the rate of pineal melatonin secretion. To investigate whether estrogen directly affects pineal adrenoceptor responsiveness, pinealocytes from 21-day-old ovariectomized rats were exposed to physiological concentrations of 17beta-estradiol (17beta-E(2)) and treated with noradrenergic agonists. Direct exposure to 17beta-E(2) reduced alpha(1)/beta-adrenoceptor-induced stimulation of melatonin synthesis and release. This effect was mediated by an estrogen-dependent inhibition of both beta-adrenoceptor-induced accumulation of cAMP and alpha(1)-adrenoceptor-induced phosphoinositide hydrolysis. Furthermore, estrogen reduced transient Ca(2+) signals elicited in single pinealocytes by alpha(1)-adrenoceptor activation or by potassium-induced depolarization. In the case of beta-adrenoceptor responsiveness, neither forskolin- nor cholera toxin-induced accumulation of cAMP were affected by previous exposure to 17beta-E(2). This indicates that estrogen effects must be exerted upstream from adenylylcyclase activation, and independent of modifications in G protein expression, therefore suggesting changes in either adrenoceptor expression or receptor-effector coupling mechanisms. Since estrogen effects upon adrenoceptor responsiveness in pineal cells was not mimicked by 17beta-E(2) coupled to bovine serum albumin and showed a latency of 48 h, this effect could be compatible with a genomic action mechanism. This is also consistent with the presence of two estrogen receptor proteins, alpha- and beta-subtypes, in female rat pinealocytes under the present experimental conditions.

Action Potentials↗

Factor V Leiden and prothrombin G20210A in relation to arterial and/or vein rethrombosis: two cases.

The factor V Leiden (FV Leiden) and prothrombin G20210A mutations, are the most common established genetic risk factors for deep vein thrombosis (DVT). However, the relationship between these mutations and arterial thrombotic syndromes (coronary heart disease, myocardial infarction, stroke) has not been established. Some studies have suggested a relationship between them, but other authors have considered it unlikely that these anomalies are a major risk factor for arterial thrombosis. From the clinical point of view, a question arises concerning the risk of repeated thrombosis in patients carrying one of these two mutations. The question is whether the recurrence is attributable to the mutations or to the presence of additional circumstantial risk factors. As the risk of repeated thrombosis varies considerably from one patient to another, decisions about long-term treatment require weighing the persistence of risk factors for vascular disease (venous and arterial), especially in selected cases such as young patients or patients with thrombosis of unusual localization.

3' Untranslated Regions↗

Selective blockade of neurokinin-2 receptors produces antidepressant-like effects associated with reduced corticotropin-releasing factor function.

The present study investigated the effects of the selective neurokinin-2 (NK2) receptor antagonist SR48968 in behavioral, electrophysiological, and biochemical tests sensitive to the action of prototypical antidepressants (fluoxetine, imipramine) or to corticotropin-releasing factor (CRF) receptor antagonists, which have been proposed recently as potential antidepressants. Results showed that SR48968 (0.3-10 mg/kg i.p.) produced antidepressant-like activity because it reduced immobility in the forced swimming test in both mice and rats, and decreased the amount of maternal separation-induced vocalizations in guinea pig pups. This latter effect appears to involve a reduction of stress-induced substance P release because SR48968 reduced the separation-induced increase in the number of neurons displaying neurokinin-1 receptor internalization in the amygdala. Furthermore, SR48968 increased the expression of the cAMP response-element binding protein mRNA in the rat hippocampus after repeated (1 mg/kg i.p., 21 days), but not acute administration. Finally, neuronal firing of the locus coeruleus (LC) and noradrenergic (NE) release in the prefrontal cortex both elicited by an uncontrollable stressor or an intraventricular administration of CRF were reduced by SR48968 (0.3-1 mg/kg i.p.). The finding that SR48968 (1 mg/kg i.p.) blocked the cortical release of NE induced by an intra-LC infusion of the preferential NK2 receptor agonist neurokinin A suggested the presence of NK2 receptors in this latter region. Importantly, SR48965 (1-10 mg/kg i.p.), the optical antipode of SR48968, which is devoid of affinity for the NK2 receptor, was inactive in all the models used. These data suggest that NK2 receptor blockade may constitute a novel mechanism in the treatment of depression and CRF-related disorders.

Animals↗

Determination of glucosinolates in rapeseed and Thlaspi caerulescens plants by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.

Liquid chromatography-atmospheric pressure chemical ionization mass spectrometry was used to identify glucosinolates in plant extracts. Optimization of the analytical conditions and the determination of the method detection limit was performed using commercial 2-propenylglucosinolate (sinigrin). Optimal values for the following parameters were determined: nebulization pressure, gas temperature, flux of drying gas, capillar voltage, corona current and fragmentor conditions. The method detection limit for sinigrin was 2.85 ng. For validation of the method the glucosinolates in reference material (rapeseed) from the Community Bureau of Reference Materials (BCR) were analyzed. The method was applied for the determination of glucosinolates in Thlaspi caerulescens plants.

Atmospheric Pressure↗

Luteinizing hormone secretion elicited in a ligand-independent activation of progesterone receptor manner at pituitary level in the rat: differential effect of two selective estrogen receptor modulators.

In the absence of progesterone, RU486 reduced basal and luteinizing hormone-releasing hormone (LHRH)-stimulated LH secretion in pituitaries from proestrous rats, a fact which evidences a ligand-independent activation of progesterone receptors (LIAPR) at pituitary level. This was also observed in pituitaries from rats treated with tamoxifen, and absent in glands from either ovariectomized or raloxifene-treated animals. Both ovariectomy or raloxifene treatment reduced the stimulatory effect of LHRH on LH secretion, while tamoxifen induced an even higher response. Prolactin (PRL) secretion was unaffected by either RU486 or LHRH, nor it was influenced by ovariectomy or raloxifene treatment. However, treatment with tamoxifen elevated PRL in all groups. These findings indicate that LIAPR is an estrogen-dependent phenomenon at the anterior pituitary of the female rat, and that tamoxifen and raloxifene present agonist and antagonist estrogen activity, respectively, at this level.

Animals↗

On the radical brook rearrangement. Reactivity of alpha-silyl alcohols, alpha-silyl alcohol nitrite esters, and beta-haloacylsilanes under radical-forming conditions

Two alkoxyl radical generation methods, lead tetraacetate treatment of alcohols and photolysis of nitrites, were applied to alpha-silyl alcohols 21 and to the corresponding nitrites 25 with a view to forming alpha-silyl alkoxyl radicals 23 and studying their possible radical Brook rearrangement to alpha-silyloxy carbon radicals 24. LTA treatment of 21 led to their quick and efficient conversion into mixed acetyl-silyl acetals 33 under very mild conditions. Photolysis of alpha-alkylmonosubstituted alpha-silyl nitrites 25 to the corresponding aldehydes is considered to proceed through alpha-silyl alkoxyl radical intermediates 23. A concerted process is, however, proposed for the case of the benzyl nitrites analogues. On the basis of these results, it is postulated that resonance stabilization can have a major influence on the evolution of alpha-silyl alkoxyl radicals: should this stabilization be possible, they quickly evolve by alpha-silyl fragmentation; otherwise, they tend to undergo radical Brook rearrangement. It was also found that the radical Brook rearrangement of alpha-silyl cyclopropyloxyl radicals generated from beta-bromoacylsilanes under standard tin-radical conditions is too slow to compete with beta-fragmentation.

Journal Article↗

Nutritional assessment in vitro and in vivo of raw and extruded peas (Pisum sativum L.).

The effects of extrusion cooking on the nutritional properties of Pisum sativum L. have been evaluated in vitro and in vivo. The treatment greatly elevated protein and starch digestibility in vitro. Also, the amounts of intact starch diminished while total free sugars increased. In addition, the levels of antinutritional factors, such as protease inhibitors and lectins, were greatly decreased. Concentrations of methionine and cystine were low in raw peas and were further reduced by extrusion treatment. The nutritional performance of rats fed extruded pea diets for 15 days was no better than that of rats given raw pea diet. This was due to the overriding effects of amino acid deficiencies in the diets. Weight gains by rats fed extruded pea diets supplemented with amino acids were, however, much higher than those achieved by rats fed supplemented raw pea diets. Food transformation index and protein efficiency ratio values were also greatly improved. Extrusion treatment did therefore significantly improve the nutritional quality of peas.

Animal Nutritional Physiological Phenomena↗