Biomedical subjects

E Ortega

Publications and source records attributed to E Ortega.

At least 19 recordsLinked to original sources

PubMed2006

Role of Hsp72 and norepinephrine in the moderate exercise-induced stimulation of neutrophils' microbicide capacity.

The influence of a single session of moderate exercise (45 min at 55% of VO(2 )max) performed by young sedentary men (23-25 years old) on the microbicidal capacity of neutrophils was compared by using both direct (killing of phagocytosed Candida albicans) and indirect (superoxide anion production measured by NBT reduction) techniques. In addition, the role of norepinephrine and heat shock protein (Hsp) 72 in the modulation of microbicide capacity of neutrophils was evaluated during the protocol of exercise and recovery period (24 h). No significant changes were found in the superoxide production after exercise. However, immediately after exercise there was an increase in the destruction of C. albicans, which remained higher than basal values 1 day later. This behaviour was similar to the changes found in the serum extracellular Hsp72 concentrations (an increase after exercise that remained higher than basal values 24 h later). In vitro, the raised physiological concentration of Hsp72 after exercise also increased the microbicide capacity of neutrophils with respect to controls and the values induced by the basal concentration of the protein. This indicates that Hsp72 is participating as a "stress mediator" of the stimulated microbicide activity during moderate exercise. However, norepinephrine is not mediating the increased killing of C. albicans during exercise.

Adult↗

PubMed2006

A functional variant in the CD209 promoter is associated with DQ2-negative celiac disease in the Spanish population.

AIM: To address the role of CD209 in celiac disease (CD) patients. Non-human leukocyte antigen (HLA) genetic factors in CD predisposition are poorly understood, and environmental factors like infectious pathogens may play a role. CD209 is a dendritic and macrophage surface molecule involved in pathogen recognition and immune activation. Recently, a functional variant in the promoter of the CD209 gene (-336A/G) has been shown to affect the transcriptional CD209 activity in vitro and it has been associated with a higher susceptibility to/or severity of infection. METHODS: The study population was composed of two case-control cohorts of 103 and 386 CD patients and 312 y 419 healthy controls as well as a panel of 257 celiac families. Genotyping for the -336A/G CD209 promoter polymorphism was performed using a TaqMan 5' allelic discrimination assay. HLA-DQ was determined by hybridization with allele specific probes. RESULTS: Initially, the case-control and familial studies did not find any association of the -336 A/G CD209 genetic variant with CD susceptibility. However, the stratification by HLA-DQ2 did reveal a significant association of CD209 promoter polymorphism in the HLA-DQ2 (-) group (carrier A vs GG in DQ2 (-) vs DQ2 (+) patients (P = 0.026, OR = 3.71). CONCLUSION: The -336G CD209 allele seems to be involved in CD susceptibility in HLA-DQ2 (-) patients. Our results might suggest a possible role of pathogens in the onset of a minor group of CD patients.

Alleles↗

PubMed2006

Effects of testosterone on brain mRNA levels of steroid 5alpha-reductase isozymes in early postnatal life of rat.

The enzyme 5alpha-reductase (5alpha-R) (EC 1.3.99.5) exists as two isoforms, 5alpha-R type 1 (5alpha-R1) and 5alpha-R type 2 (5alpha-R2), and both are present in the brain. 5alpha-R1 has been proposed as a constitutive enzyme that essentially plays a catabolic and neuron protective role whereas 5alpha-R2 has been associated with sexually dimorphic functions of the male. In this work, we studied the effects of testosterone (T), the masculinizing hormone of the central nervous system (CNS), on mRNA levels of both 5alpha-R isoforms in the prefrontal cortex of male and female rats during the postnatal sexual differentiation of the CNS in the rat, using one-step quantitative RT-PCR coupled with laser-induced fluorescence capillary electrophoresis (LIF-CE). We found an increase in 5alpha-R2 mRNA levels in both male and female rats after T treatment, while 5alpha-R1 mRNA levels were decreased in the same experimental conditions. Our results clearly indicated that T regulates the expression of both 5alpha-R1 and 5alpha-R2 genes in an opposite manner and independently of the sex. This could point to a crucial role of T in the sexual dimorphism for both 5alpha-R isozymes in the neonatal brain. These results open up a new research line that could improve understanding of the role of 5alpha-R isozymes in the physiology of the CNS.

Animals↗

PubMed2006

Steroid 5alpha-reductase isozymes in the adult female rat brain: central role of dihydrotestosterone.

The enzyme 5alpha-reductase (5alpha-R) (EC 1.3.99.5) exists as two isoforms, 5alpha-R type 1 (5alpha-R1) and 5alpha-R type 2 (5alpha-R2). 5alpha-R1 has been associated with catabolic functions whereas 5alpha-R2 has been associated with sexually dimorphic functions of the male. We recently demonstrated that both 5alpha-R isozymes are present in the central nervous system (CNS) of the adult male rat and are regulated in an opposing way by androgens. This finding raises the question as to whether both isozymes play a role in the sexual dimorphism of the CNS, besides other functions. To test this hypothesis, it is essential to study the regulation of both isozymes by androgens in the female. In this work, we studied the effects of testosterone (T) and dihydrotestosterone (DHT) on mRNA levels of both 5alpha-R isoforms in the prefrontal cortex of the adult female rat by one-step quantitative RT-PCR coupled with laser-induced fluorescence capillary electrophoresis. Our results demonstrate for the first time that 5alpha-R2 mRNA is slightly regulated by T and DHT in females. Surprisingly, 5alpha-R1 mRNA is not regulated by T in the intact female, whereas it is very positively regulated by DHT, a more potent androgen than T. These data indicate the great sexual dimorphism in the CNS with respect to both 5alpha-R isozymes, and suggest a crucial role of DHT in the sexual dimorphism of the CNS in the female. These results open up a new research line that may lead to a better understanding of the physiology of the CNS.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2005

Effect of the preventive-therapeutic administration of melatonin on mammary tumour-bearing animals.

Melatonin has been reported to be involved in the feedback between neuroendocrine and immune functions and to exert oncostatic actions. Likewise, this hormone seems to lengthen life span in healthy animals. As of present, most studies have analysed the therapeutic effect of melatonin on cancer growth, but few have tested the preventive effect of melatonin in reducing the risk of cancer. Thus, the aim of this study was to evaluate the preventive-therapeutic effects of melatonin on rats with DMBA-induced mammary tumours, and to examine the effect of melatonin on the first line of cell defence against cancer (macrophages and NK cells) and on some of the neuroendocrine factors that are involved in the development of tumours (prolactin and catecholamines). Melatonin treatment (5 mg/day/animal) began one month prior to DMBA (9,10-dimethyl-1,2-benzanthracene) administration to females Sprague Dawley rats. It was found that the treatment led to an increase in survival and in latency time in the tumour-bearing rats. Although the melatonin treatment did not influence either the phagocytic capacity of macrophages or the number of peripheral blood NK cells, it did stabilise the levels of prolactin by returning the concentrations of this hormone to those of the healthy animals. We conclude that melatonin can exert an oncostatic action, lengthening the survival time of mammary tumour-bearing animals, and suggest that this effect is due, at least in part, to regulating the neuroendocrine parameters of tumour-bearing animals, bringing them closer to their optimal physiological status.

Adjuvants, Immunologic↗

PubMed2005

Melatonin increases the survival time of animals with untreated mammary tumours: neuroendocrine stabilization.

The aim of this study was to evaluate the therapeutic effect of melatonin, the main hormone of the pineal gland, on rats with advanced and untreated mammary tumours. Mammary tumours were chemically induced in Sprague-Dawley rats with the carcinogen 9,10-dimethyl-1,2-bezanthracene (DMBA). After the appearance of tumours the effect of melatonin (5 mg/ml per rat per day) was then evaluated on the survival time, tumour multiplicity, and tumour volume until the death of the animals. In addition, the variations in prolactin, noradrenaline and adrenaline concentrations, and in the percentage of NK cells were evaluated after one month of the treatment with melatonin. Daily administration of melatonin increased significantly the survival time of tumour-bearing animals (p<0.05 with respect to the control non-melatonin-receiving rats). The increased survival time did not correlate, however, with changes in either tumour multiplicity or tumour growth rate. Animals with mammary tumours exhibited an increase (p<0.05 with respect to healthy animals) in prolactin and catecholamine concentrations. The administration of melatonin stabilized the hormone levels, returning them to those in the basal-healthy animals. Rats with mammary tumours also presented lower percentages of NK cells, which were not increased by the administration of melatonin. The results strongly suggest that melatonin per se is beneficial during advanced breast cancer. It increases survival time, maybe by improving the homeostatic and neuroendocrine equilibrium which is imbalanced during advanced breast cancer.

9,10-Dimethyl-1,2-benzanthracene↗

PubMed2005

CTLA4/CT60 polymorphism is not relevant in susceptibility to autoimmune inflammatory intestinal disorders.

The aim of this work was to investigate the possible influence of the recently described CT60 A/G dimorphism of the CTLA4 (cytotoxic T-lymphocyte antigen 4) gene in the susceptibility to two different autoimmune inflammatory intestinal disorders, inflammatory bowel disease (IBD) and celiac disease. We analyzed a case-control cohort composed of 528 Spanish patients with IBD (284 with Crohn disease and 244 with ulcerative colitis) and 454 unrelated healthy individuals, and additionally a group of 90 celiac disease families. CT60 genotyping was performed with a TaqMan 5' allelic discrimination assay. After comparing patients with IBD with the control population, we found no significant deviation in the distribution of the alleles or genotypes of CTLA4/CT60 dimorphism. In addition, by means of familial and case-control analysis, no evidence for a statistically significant association was observed between CTLA4/CT60 and celiac disease susceptibility. Therefore, our results suggest that the CTLA4/CT60 polymorphism does not play a major role in inflammatory intestinal disorders.

Antigens, CD↗

PubMed2005

Melatonin, lipid peroxidation, and age in heterophils from the ring dove (Streptopelia risoria).

Numerous recent studies have shown the ability of physiological as well as all pharmacological concentrations of melatonin to prevent oxidative stress. We have found that incubating avian heterophils from young birds with a pharmacological concentration of 100 microM (23x10(6) pg/ml) melatonin reduced superoxide anion levels by modulating the activity of superoxide dismutase while also enhancing phagocytosis. There was also a decline in lipid peroxidation levels with both physiological and pharmacological concentrations of this indolamine. In the present work, we evaluated malonaldehyde (MDA) levels as an indicator of lipid peroxidation (both basal and antigen-induced) in young and old animals (ring doves) at different times of day (16:00 and 00:00) and with two incubation times (15 and 60 min). The lipid peroxidation was also measured in heterophils from old animals, incubated with the physiological concentrations of melatonin measured in young animals (50 and 300 pg/ml, diurnal and nocturnal, respectively). The results, expressed as nmol MDA/mg protein, show that MDA levels were higher in heterophils of old animals than in the young birds in all the experimental groups studied at both 16:00 and 00:00 (00:00 is the time at which the lowest peroxidation levels were obtained). Incubation with melatonin was found to reduce MDA levels, with the maximum reduction being after the 60?min incubation time and the nocturnal melatonin concentration. At both concentrations (diurnal and nocturnal), melatonin also counteracted the enhancement of MDA levels caused by latex beads, with the effect being greater at the longer incubation time. In conclusion, the results are further evidence of the antioxidant effect of melatonin even at physiological concentrations, and suggest its utility as a therapeutic agent in some pathological processes associated with age.

Aging↗

PubMed2005

Poly (ADP-ribose) polymerase-1 haplotypes are associated with coeliac disease.

In coeliac disease (CD) there is an inflammatory status of the intestinal mucosa because of a high expression of proinflammatory mediators. The nuclear protein poly (ADP-ribose) polymerase-1 (PARP-1) has been implicated in the initial inflammatory response by modulating transcription of inflammation-related genes. The aim of this work was to investigate the role of PARP-1 gene promoter region haplotypes in relation to coeliac disease susceptibility. We analysed a coeliac population consisting of a case-control panel with 120 CD patients and 311 healthy blood donors. A CA microsatellite, as haplotype-defining variant of the whole PARP-1 promoter, was typed using a polymerase chain reaction (PCR) method combined with fluorescence technology. We considered two promoter haplotypes: A defined by short CA alleles (83-87 bp) and B defined by long CA alleles (89-101 bp). Haplotype A was significantly increased within the coeliac patients group (P = 0.007 OR 1.6 95%CI 1.12-2.35). Additionally, we observed a significant dose effect, showing homozygous individuals for haplotype A higher risk for CD susceptibility (P = 0.007, OR 1.79 95%CI 1.14-2.82). Our results provide the first evidence that PARP-1 haplotypes are related with coeliac disease susceptibility.

Autoimmune Diseases↗

PubMed2005

[Enzyme replacement therapy in Fabry's disease].

We report a 56-year-old man with history of chronic renal failure, who was diagnosed to have Fabry's disease after performing a percutaneous kidney biopsy. The diagnosis was confirmed by the deficient level of activity of alpha-galactosidase A and by the identification of the mutation. A enzime replacement therapy with alpha-galactosidase A was administered. After 18 months of treatment, a second kidney biopsy was performed showing renal deposits of globotriaosylceramide (we did not evaluate the percentage of histologic clearance of the deposits). Six months after the end of the therapy, a reduction in the impairment of renal function is observed, and the classic manifestations of the disease are absent.

Adult↗

PubMed2004

Norepinephrine as mediator in the stimulation of phagocytosis induced by moderate exercise.

During intensive exercise the stimulation of phagocytosis is mediated by "stress hormones". During moderate exercise, however, such mediation is less clear. The influence of moderate exercise (45 min at 55% maximal oxygen uptake) on the phagocytic capacity of neutrophils was evaluated in sedentary men. The exercise stimulated phagocytosis of Candida albicans, and the stimulation was maintained for at least 24 h. The possible neuroendocrine mediators were then investigated. Stimulation of phagocytosis was found after incubating neutrophils from sedentary individuals, who were in a basal state, with plasma from exercised individuals. Immediately after exercise, there was a significant increase in the concentration of norepinephrine, but not of epinephrine or cortisol. Incubation of neutrophils with this post-exercise physiological concentration of norepinephrine also stimulated phagocytosis, and the effect was blocked by both propranolol and phentolamine. The norepinephrine-augmented phagocytosis was accompanied by an increase in intracellular levels of cAMP, but not of cGMP or calcium. In conclusion, moderate exercise performed by sedentary people stimulates the phagocytic capacity of neutrophils, and the stimulation lasts for at least 24 h. Norepinephrine mediates the stimulation, although other mechanisms could be involved during the recovery period.

Adult↗

PubMed2004

Emerging cardiovascular risk factors in subclinical hypothyroidism: lack of change after restoration of euthyroidism.

Subclinical hypothyroidism (SH) is a frequent condition that may be associated with increased cardiovascular risk. There is current interest in determining the effect, if any, of substitutive therapy with l-thyroxine (L-T4) on cardiovascular risk factors in SH and, particularly, on those associated with emerging cardiovacular risk, such as apolipoprotein (apo) B, lipoprotein (Lp) (a), total homocysteine (t-Hcy), and C-reactive protein (CRP). Thus, the aim of this study was to assess the impact of euthyroidism restoration on these emerging risk factors in SH. Forty-two patients diagnosed with SH were consecutively recruited before treatment. These patients were treated with L-T4 for 3 to 6 months with the dose necessary to restore euthyroidism. Lp(a), fasting and postmethionine (n = 28) t-Hcy, and CRP did not change with substitutive therapy, regardless of the respective baseline values, and the decrease in apo B paralleled that of low-density lipoprotein (LDL) cholesterol. Similarly, no treatment effect was observed on homocysteine or CRP in patients with thyrotropin-stimulating hormone (TSH) >10 mIU/L. Monitoring of emerging risk factors did not offer additional arguments for treating patients with SH and, thus, is not justified in their clinical management.

Adult↗

PubMed2004

A functional variant of IFNgamma gene is associated with coeliac disease.

In coeliac disease (CD) a profile of proinflammatory cytokines are secreted interferon gamma (IFNgamma) being one of the most important. A dinucleotide polymorphism consisting of a variable number of CA repeats related with IFNgamma production levels, has been reported on the first intron of the IFNgamma gene. The aim of this study was to analyse the influence of the functional IFNgamma CA repeats in CD predisposition through familial and case-control studies. The familial analysis showed that the 124 bp allele was significantly more transmitted to the affected offspring (P=0.02), while the 126 bp allele showed a statistically significant nontransmission pattern (P=0.01). Nevertheless, in the case-control analysis, we could not find a direct association of CA repeats with CD. This fact might be due to parent-of-origin effect in the IFNgamma CA polymorphism. Our data suggest a possible role of IFNgamma CA polymorphism in CD susceptibility.

Alleles↗

PubMed2004

Consensus conference on chronic viral hepatitis and HIV infection: updated Spanish recommendations.

Chronic hepatitis B and C represent a leading cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected patients worldwide. New treatment options against both hepatitis B (HBV) and C (HCV) viruses have prompted us to update previous recommendations for the management of coinfected individuals. Fifteen topics (nine related to HCV, five to HBV and one to both viruses) were selected for this purpose. A panel of Spanish experts in the field was invited to review these areas and propose specific recommendations, which were scored according to the Infectious Disease Society of America (IDSA) grading system. These guidelines represent a comprehensive and updated overview on the management of hepatitis B and C in HIV-infected patients.

Anti-HIV Agents↗

PubMed2004

Sonographically guided 11-G directional vacuum-assisted breast biopsy as an alternative to surgical excision: utility and cost study in probably benign lesions.

PURPOSE: To evaluate the utility and economic costs of the 11-G vacuum-assisted biopsy probe under ultrasound (US) guidance as an alternative to surgical excision in patients with probably benign lesions. MATERIAL AND METHODS: US-guided 11-G vacuum-assisted biopsy was performed in 102 probably benign breast lesions in 97 women who refused radiological follow-up. Complete removal of the lesion was intended in all cases. Open biopsy was done if questionable pathologic findings were present. Treatment was indicated if the diagnosis was malignant. Economic costs were estimated taking into consideration monetary expenses generated to the public health system, as well as expenses for the patients receiving percutaneous and open surgical biopsy. RESULTS: Median patient age was 42 years (range 18-77). Median lesion size was 14.7 mm (range 6-30 mm). Complete removal of the lesion seen at imaging was achieved in 72.5% of cases. Adequate tissue samples for histopathological evaluation were obtained in all cases. Surgical biopsy was recommended in nine cases. One patient diagnosed with mucinous carcinoma underwent immediate surgical treatment. The remaining 87 women with 92 lesions were included in a follow-up program. Economic cost of the 11-G vacuum-assisted percutaneous biopsy was 82% lower than the surgical biopsy (total savings in this series: 136,402.84 euros). Time spent for the patient was 71% less in percutaneous biopsy than in surgery. CONCLUSION: Ultrasound-guided 11-G directional vacuum-assisted breast biopsy is an accurate and less expensive procedure that can be used as an alternative to open surgical excision in a selected group of patients.

Adenocarcinoma, Mucinous↗

PubMed2004

Precise quantitation of steroid 5alpha lambda pi eta alpha-reductase type 1 mRNA levels by RT-PCR in female rat liver.

The liver is a multifunctional organ capable of steroid hormone catabolism. The steroid metabolizing enzyme activities have been identified in the liver and it has been demonstrated that neonatal testicular androgens irreversibly program several hepatic enzyme activities in the rat including 5alpha-reductase (5alpha-R). In this paper we have applied a quantitative RT-PCR method coupled to laser-induced fluorescence capillary electrophoresis (LIF-CE) to measure the mRNA levels of 5alpha-R type 1 isozyme (5alpha-R1) in the liver of female intact and ovariectomized rats. Both groups were treated with testosterone (T) to study the possible regulation of 5alpha-R1 by androgens in females and to allow comparison with our previous findings in the liver of male rats. Our results demonstrate that the 5alpha-R1 mRNA isozyme is higher in the liver of female rats than in males and that the regulation of 5alpha-R1 mRNA by T is different in the liver of female than in male rats. Finally, our results could point to hepatic 5alpha-Reductase participation in the female not only in the catabolism of steroids with delta4,5 double bond, but also in other physiological functions such as the production of 3alpha,5alpha-reduced metabolites of progesterone and deoxycorticosterone (DOC), potent allosteric modulators of GABA(A) receptors.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗

PubMed2004

CA microsatellite polymorphism of the nuclear factor kappa B1 gene in celiac disease.

In the present work, we investigate the possible effect of a CAn microsatellite polymorphism in the nuclear factor kappa B1 (NFKB1) gene on predisposition to celiac disease (CD). Seventy-eight Spanish families with CD were genotyped using a polymerase chain reaction (PCR)-fluorescent method, and the transmission patterns of different CAn alleles were analysed. Furthermore, in order to type the CAn polymorphism more accurately, samples between 126 and 144 bp were cloned and sequenced. A trend of association with the 132-bp allele was found (P = 0.02). This allele was more frequently transmitted to affected sibs, although the results of statistical tests were not significant after correction for multiple comparisons. After sequencing, we found that the 132-, 138- and 142-bp alleles had two As at the end of the CA microsatellite, with the other alleles presenting the described pattern (NCB1 nucleotide U60337) for the microsatellite repeats. These results suggest that the NFKB1 CAn microsatellite does not play a major role in CD susceptibility. In addition, a more detailed molecular characterization of the CA microsatellite is described.

Base Sequence↗

PubMed2004

A putative new endophytic nitrogen-fixing bacterium Pantoea sp. from sugarcane.

AIMS: To isolate and identify endophytic nitrogen-fixing bacteria in sugarcane growing in Cuba without chemical fertilizers. METHODS AND RESULTS: Two N2-fixing isolates, 9C and T2, were obtained from surface-sterilized stems and roots, respectively, of sugarcane variety ML3-18. Both isolates showed acetylene reduction and H2 production in nitrogen-free media. Nitrogenase activity measured by H2 production was about 15 times higher for isolate 9C than for T2 or for Gluconoacetobacter diazotrophicus (PAL-5 standard strain, ATCC 49037). The nifH gene segment was amplified from both isolates using specific primers. Classification of both T2 and 9C was made on the basis of morphological, biochemical, PCR tests and 16S rDNA sequence analysis. CONCLUSIONS: Isolate 9C was identified as a Pantoea species from its 16S rDNA, but showed considerable differences in physiological properties from previously reported species of this genus. For example, 9C can be cultured over a wide range of temperature, pH and salt concentration, and showed high H2 production (up to 67.7 nmol H2 h(-1) 10(10) cell(-1)). Isolate T2 was a strain of Gluconacetobacter diazotrophicus. SIGNIFICANCE AND IMPACT OF THE STUDY: A new N2-fixing endophyte, i.e. Pantoea, able to produce H2 and to grow in a wide range of conditions, was isolated from sugarcane stem tissue and characterized. The strain with these attributes may well be valuable for agriculture.

Cuba↗