[Endoscopic capsule: present and future].
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Endoscopes, Gastrointestinal↗
Biomedical subjects
B González
Publications and source records attributed to B González.
Smoking in young adolescents: an approach with multilevel discrete choice models.
STUDY OBJECTIVE: To understand the context for tobacco smoking in young adolescents, estimating the effects of individual, family, social, and school related factors. DESIGN: Cross sectional analysis performed by multilevel logistic regression with pupils at the first level and schools at the second level. The data came from a stratified sample of students surveyed on their own, their families' and their friends' smoking habits, their schools, and their awareness of cigarette prices and advertising. SETTING: The study was performed in the Island of Gran Canaria, Spain. PARTICIPANTS: 1877 students from 30 secondary schools in spring of 2000 (model's effective sample sizes 1697 and 1738). MAIN RESULTS: 14.2% of the young teenagers surveyed use tobacco, almost half of them (6.3% of the total surveyed) on a daily basis. According to the ordered logistic regression model, to have a smoker as the best friend increases significantly the probability of smoking (odds ratio: 6.96, 95% confidence intervals (CI) (4.93 to 9.84), and the same stands for one smoker living at home compared with a smoking free home (odds ratio: 2.03, 95% CI 1.22 to 3.36). Girls smoke more (odds ratio: 1.85, 95% CI 1.33 to 2.59). Experience with alcohol, and lack of interest in studies are also significant factors affecting smoking. Multilevel models of logistic regression showed that factors related to the school affect the smoking behaviour of young teenagers. More specifically, whether a school complies with antismoking rules or not is the main factor to predict smoking prevalence in schools. The remainder of the differences can be attributed to individual and family characteristics, tobacco consumption by parents or other close relatives, and peer group. CONCLUSIONS: A great deal of the individual differences in smoking are explained by factors at the school level, therefore the context is very relevant in this case. The most relevant predictors for smoking in young adolescents include some factors related to the schools they attend. One variable stood out in accounting for the school to school differences: how well they enforced the no smoking rule. Therefore we can prevent or delay tobacco smoking in adolescents not only by publicising health risks, but also by better enforcing no smoking rules in schools.
Adolescent↗
Protein variants of skeletal muscle regulatory myosin light chain isoforms: prevalence in mammals, generation and transitions during muscle remodelling.
The regulatory myosin light chains (rMLCs) of mammalian skeletal muscle display protein diversity arising from the existence of different isotypes and protein phosphorylation. Two-dimensional electrophoresis and immunoblotting allowed us to identify three variants of the slow and fast rMLC isoforms (designated LC2s, LC2s1, LC2s2, and LC2f, LC2f1, LC2f2, respectively, from less to more acidic). This study aimed to characterize their prevalence among different species and muscle types, the mechanism(s) of their generation and their transitions during fast-to-slow fibre type switching. In vitro dephosphorylation and back-phosphorylation experiments and mass spectrometric analysis of tryptic digests indicate that: (1) both acidic variants, within each isoform, contain a phosphorylated peptide, (2) all variants of each isoform share identical tryptic peptides, (3) only one phosphopeptide is present per isoform, and (4) the intermediate-acidic variants of both isoforms contain the same peptide in their phosphorylated and non-phosphorylated forms. The data indicate that the triad pattern of variants results from two partially superimposed doublets of phosphorylated/non-phosphorylated pairs. Continuous, low-frequency electrical stimulation of rat extensor digitorum longus muscle changed the relative proportions of variants within each isoform towards those of the soleus. It is suggested that the doublets of phosphorylated/non-phosphorylated pairs are involved in rMLC exchange during sarcomere remodelling.
Alkaline Phosphatase↗
Cobaltocenium-functionalized poly(propylene imine) dendrimers: redox and electromicrogravimetric studies and AFM imaging.
The first four generations of cobaltocenium-functionalized, diaminobutane-based poly(propylene imine) dendrimers DAB-dend-Cb,(PFb)x (x = 4, 8, 16, and 32; Cb=[Co(eta5-C5H4CONH)(eta5-C5H5)] (1-4) have been synthesized and characterized. The redox activity of the cobaltocenium centers in 1-4 has been characterized by using cyclic voltammetry and the electrochemical quartz-crystal microbalance (EQCM). All of the dendrimers exhibit reversible redox chemistry associated with the cobaltocenium/cobaltocene redox couple. Upon reduction. the dendrimers exhibit a tendency to electrodeposit onto the electrode surface, which is more pronounced for the higher generations. Pt and glassy carbon electrodes could be modified with films derived from 1-4,exhibiting a well-defined and persistent electrochemical response. EQCM measurements show that the dendrimers adsorb, at open circuit, onto platinum surfaces at monolayer or submonolayer coverage. Cathodic potential scanning past -0.75 V at which the cobaltocenium sites are reduced, gave rise to the electrodeposition of multilayer equivalents of the dendrimers. The additional material gradually desorbs upon re-oxidation so that only a monolayer equivalent remains on the electrode surface. Changes in film morphology as a function of dendrimer generation and surface coverage were studied by using admittance measurements of the quartz-crystal resonator on the basis of its electrical equivalent circuit, especially in terms of its resistance parameter. In general, we find that films of the lower dendrimer generation 1 behave rigidly, whereas those of the higher generation 4 exhibit viscoelastic behavior with an intermediate behavior being exhibited by 2 and 3. Using tapping-mode atomic force microscopy (AFM). we have been able to obtain molecularly resolved images of dendrimer 4 adsorbed on a Pt(111) electrode.
Journal Article↗
Expression of 27 kDa heat shock protein (Hsp27) in immature rat brain after a cortical aspiration lesion.
The 27 kDa heat shock protein (Hsp27) is a well-known member of the astroglial response to injury, playing a protective role against oxidative stress, apoptosis, and cytoskeletal destruction. Although several studies have been focused on the damaged adult brain, little is known about Hsp27 expression in the immature brain. In this work, we have examined the spatiotemporal pattern of Hsp27 expression in the normal postnatal rat brain following a cortical aspiration lesion at postnatal day 9. In the immature brain, Hsp27 is mainly observed in the internal capsule, although some scattered cells are also found in the ependyma, the corpus callosum, the septum, and hypothalamic glia limitans. In the internal capsule, Hsp27 expression is developmentally regulated, being significantly decreased from postnatal day 14. After a cortical aspiration lesion, de novo expression of Hsp27 is observed in cortical injured areas as well as in the secondary affected thalamus. In the cortex, expression of Hsp27 is first seen at day 1 postlesion (PL) surrounding the neurodegenerative area, becoming restricted to the glial scar at longer survival times. Although a pulse-like expression of Hsp27 is observed in some microglial cells at day 1 PL, most Hsp27-labeled cells are reactive astrocytes, which show GFAP overexpression and coexpress vimentin from day 3 PL. In the thalamus, astroglial Hsp27 expression is delayed, being first observed at day 5 PL. Thalamic Hsp27-labeled astrocytes do not show vimentin expression. Our observations demonstrate astroglial expression of Hsp27 in areas of tissue damage following postnatal traumatic injury, suggesting an involvement of this cytoskeleton-stabilizing protein in the remodeling processes following postnatal brain damage.
Aging↗
Glial activation in the immature rat brain: implication of inflammatory transcription factors and cytokine expression.
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Aging↗
Profile of the population of Spain with respect to the smoking habit, period 1993-1997.
The consumption of tobacco has become by far the main avoidable cause of disease and premature death in Spain. There is a trend towards picking up the tobacco habit at an earlier age for both males and females. The number of women smokers is rising, particularly in the younger age groups (45% of women between the ages of 16 and 22 claim to be smokers) almost equalling male levels, which are remaining constant. The objective of this study is to profile current smokers, former smokers and never smokers among Spanish men and women, based on subject characteristics, and compare the profiles estimated for 1993, 1995 and 1997. We use a two-level nested logistic regression model to model the adoption and cessation processes of the smoking habit. The first level or branch discriminates between persons who have never been smokers and people who have been smokers or who are smokers at present. The second level is to discriminate between present smokers and former smokers (succeeded in the cessation process). The results show that the variables which define the profile of smokers include so-called stress-related factors, if the individual is separated or divorced, whether she is unemployed. The cessation process accelerates with age and is stimulated by the diagnosis of chronic disease, particularly heart disease. Our results, which are fairly stable from 1993 to 1997, should provide guidelines in the development of prevention and control of tobacco consumption health policies.
Adolescent↗
Triflusal posttreatment inhibits glial nuclear factor-kappaB, downregulates the glial response, and is neuroprotective in an excitotoxic injury model in postnatal brain.
BACKGROUND AND PURPOSE: Nuclear factor-kappaB (NF-kappaB) and the signal transducer and activator of transcription 3 (STAT3) are important transcription factors regulating inflammatory mechanisms and the glial response to neural injury, determining lesion outcome. In this study we evaluate the ability of triflusal (2-acetoxy-4-trifluoromethylbenzoic acid), an antiplatelet agent inhibitor of NF-kappaB activation, to improve lesion outcome after excitotoxic damage to the immature brain. METHODS: Postnatal day 9 rats received an intracortical injection of the excitotoxin N-methyl-D-aspartate (NMDA) and oral administration of triflusal (30 mg/kg) either as 3 doses before NMDA injection (pretreatment) or as a single dose 8 hours after NMDA injection (posttreatment). After survival times of 10 and 24 hours, brains were processed for toluidine blue staining, tomato lectin histochemistry, and glial fibrillary acidic protein, NF-kappaB, and STAT3 immunocytochemistry. RESULTS: NMDA-lesioned animals that were not treated with triflusal showed activation of NF-kappaB in neuronal cells at first and in glial cells subsequently. Animals that received pretreatment with triflusal showed a strong downregulation of neuronal and glial NF-kappaB but a similar development of the glial response and an equivalent lesion volume compared with nontreated animals. In contrast, animals receiving triflusal posttreatment showed increased early neuronal NF-kappaB but a reduction in the subsequent glial NF-kappaB, accompanied by important downregulation of the microglial and astroglial response and a drastic reduction in the lesion size. STAT3 activation was not affected by triflusal treatment. CONCLUSIONS: Triflusal posttreatment diminishes glial NF-kappaB, downregulates the glial response, and improves the lesion outcome, suggesting a neuroprotective role of this compound against excitotoxic injury in the immature brain.
Administration, Oral↗
Cooperation between low density lipoproteins and IGF-I in the promotion of mitogenesis in vascular smooth muscle cells.
Low density lipoproteins (LDL) are an independent risk factor for atherosclerosis and show synergism with some growth factors in vascular smooth muscle cell (VSMC) proliferation. IGF-I has mitogenic actions on VSMC, which, in turn, show enhanced expression of IGF-I and its receptor when exposed to hypercholesterolemic diets in vivo. To investigate the molecular basis of a possible interaction between LDL and the IGF-I signaling system in VSMC, we used A10 cells, where synergism between both factors in DNA synthesis was demonstrated. IGF-I activates phosphatidylinositol 3-kinase (PI3 kinase) and extracellular signal-regulated MAPK pathways in A10 cells, although insulin receptor substrate-1 (IRS-1)-associated PI3 kinase is more closely linked to IGF-I induced proliferation. LDL, in pathophysiological concentrations, affect the IGF-I signaling pathway at multiple levels: 1) they induce phosphorylation of IGF-I receptor beta and IRS-1 in a time- and dose-dependent manner; 2) they up-regulate IRS-1-associated PI3 kinase/Akt activation in response to IGF-I at early times; and 3) they show additive effects with IGF-I on extracellular signal-regulated MAPK 1/2 phosphorylation. These actions are not present in very low density lipoprotein treatments. Taken together, these results indicate specific cooperation between LDL and the IGF-I signaling pathways and may represent a more general mechanism through which proatherogenic lipoproteins modulate VSMC response to growth factors.
Animals↗
High prevalence of RET tyrosine kinase activation in Mexican patients with papillary thyroid carcinomas.
RET/PTC oncogene expression is restricted to papillary thyroid carcinomas (PTC). At least three forms of this oncogene have been described. These are generated by the rearrangement of the 5'-terminal region of different expressed genes with the tyrosine-kinase (TK) domain of the ret proto-oncogene. Several studies showing the correlation between the expression of this oncogene, clinical outcome, and histological subtypes have been published. Thirty-five paraffin-embedded PTC samples from patients without a history of radiation exposure were studied. Immunohistochemistry (IHC) and in situ hybridization (ISH) were used to determine a possible correlation between RET activation, clinical outcome, and tumor subtype. Almost half of the studied cases presented with tumoral extension or metastases. Ret gene transcripts and protein were found in all PTC variants as well as in their corresponding metastases. In contrast, none of the follicular adenomas, goiters, or normal follicular cells from the thyroid gland showed evidence of ret activation. We observed a high frequency of ret expression in PTCs, suggesting that ret activation is a common event in nonradiation-related PTC from Mexican patients.
Adult↗
The crystal structure of tetrameric methionine adenosyltransferase from rat liver reveals the methionine-binding site.
Most of the transmethylation reactions use the same methyl donor, S-adenosylmethionine (SAM), that is synthesised from methionine and ATP by methionine adenosyltransferase (MAT). In mammals, two MAT enzymes have been detected, one ubiquitous and another liver specific. The liver enzyme exists in two oligomeric forms, a tetramer (MAT I) and a dimer (MAT III), MAT I being the one that shows a higher level of affinity for methionine but a lower SAM synthesis capacity. We have solved the crystal structure of rat liver MAT I at 2.7 A resolution, complexed with a methionine analogue: l-2-amino-4-methoxy-cis-but-3-enoic acid (l-cisAMB). The enzyme consists of four identical subunits arranged in two tight dimers that are related by crystallographic 2-fold symmetry. The crystal structure shows the positions of the relevant cysteine residues in the chain, and that Cys35 and Cys61 are perfectly oriented for forming a disulphide link. This result leads us to propose a hypothesis to explain the control of MAT I/III exchange and hence, the effects observed on activity. We have identified the methionine-binding site into the active-site cavity, for the first time. The l-cisAMB inhibitor is stacked against Phe251 aromatic ring in a rather planar conformation, and its carboxylate group coordinates a Mg(2+), which, in turn, is linked to Asp180. The essential role of the involved residues in MAT activity has been confirmed by site-directed mutagenesis. Phe251 is exposed to solvent and is located in the beginning of the flexible loop Phe251-Ala260 that is connecting the N-terminal domain to the central domain. We postulate that a conformational change may take place during the enzymatic reaction and this is possibly the reason of the unusual two-step mechanism involving tripolyphosphate hydrolysis. Other important mechanistic implications are discussed on the light of the results. Moreover, the critical role that certain residues identified in this study may have in methionine recognition opens further possibilities for rational drug design.
Acid Anhydride Hydrolases↗
Oral administration of the anti-inflammatory substance triflusal results in the downregulation of constitutive transcription factor NF-kappaB in the postnatal rat brain.
In this study we have evaluated the in vivo ability of triflusal (2-acetoxy-4-tri-fluoromethylbenzoic acid) to inhibit constitutive nuclear factor-kappa B (NF-kappaB) activation in the brain of postnatal rats. One week old Long-Evans black hooded rat pups received three oral administrations of triflusal (30 mg/kg) and were sacrificed at 9 days of age. After fixation, brains were cut in a cryostat and processed immunocytochemically for the demonstration of NF-kappaB. In control postnatal rats, NF-kappaB is constitutively present in some neuronal populations and in glial cells of white matter tracts. In contrast, triflusal treated rats showed a drastic downregulation of neuronal and glial NF-kappaB, both in the number of labelled cells and in the intensity of staining. The inhibition of NF-kappaB activation could be an important step in the modulation of inflammatory processes occurring after several pathological conditions.
Administration, Oral↗
Mixed Ferrocene-Cobaltocenium Dendrimers: The Most Stable Organometallic Redox Systems Combined in a Dendritic Molecule This work was supported by the Dirección General de Enseñanza Superior e Investigación Científica (PB-97-0001). We are grateful to M. J. Vicente and Dr. M. T. Alonso for valuable discussions on ESI-MS.
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Journal Article↗
Degradation of 2,4,6-trichlorophenol via chlorohydroxyquinol in Ralstonia eutropha JMP134 and JMP222.
The aim of this work was to study the catabolic pathway of the pollutant 2,4,6-trichlorophenol in Ralstonia eutropha JMP134. 2,6-dichlorohydroquinone was detected as transient intermediate. Enzymatic transformations of 6-chlorohydroxyquinol to 2-chloromaleylacetate, and of this compound to maleylacetate were detected in crude extracts. Therefore, the degradation of 2,4,6-trichlorophenol proceeded through an hydroxyquinol pathway, different from the other chloroaromatic pathways reported in this strain. The same results were observed in two other 2,4,6-trichlorophenol degrading strains: R. eutropha JMP222, a derivative of strain JMP134 lacking the chlorocatechol catabolism-encoding pJP4 plasmid, and a river isolate, Ralstonia sp. PZK.
Biodegradation, Environmental↗
Stress proteins of 70 kDa in chronically exercised skeletal muscle.
Skeletal muscle fibres of untrained animals experience a stress response following exercise. This study was aimed at investigating whether chronic exercise modulates stress proteins of 70 kDa (HSP70s) in skeletal muscle. In the soleus muscle of Wistar rats, adherence to an incremental programme of treadmill running (IPTR) of 3 months duration up-regulated the levels of the beta-subunit of the mitochondrial F1-ATPase and those of HSP72, GRP75 and GRP78. Neither beta-F1-ATPase nor sarcoplasmic reticulum Ca2+-ATPase levels changed with training in the extensor digitorum longus (EDL) muscle. However, HSP70s increased during training. In soleus muscle slices of animals sacrificed 3 days after completing the IPTR, HSP72 and GRP75 were synthesized at lower rates than in sedentary animals while the GRP78 synthesis rate increased. Trained, rested animals also experienced a stress response following acute exercise of lower intensity than that of the actual training sessions. The data suggest that up-regulation of HSP70s by chronic exercise depends upon continued physical activity. Furthermore, the inverse correlation between levels and rates of synthesis of HSP72 during rest periods suggests the operation of a feedback regulatory loop aimed at reestablishing the threshold levels characteristic of unstressed fibres.
Animals↗
Anabolic steroid and gender-dependent modulation of cytosolic HSP70s in fast- and slow-twitch skeletal muscle.
Besides their clinical uses, anabolic steroids (AASs) are self-administered by athletes to improve muscle mass and sports performance. The biological basis for their presumed effectiveness at suprapharmacological doses, however, remains uncertain. Since the expression of high levels of some stress proteins (HSPs) has been associated with an increased tolerance to stress and chronic exercise up-regulates HSP72 in skeletal muscle, this investigation was aimed at testing whether the administration of suprapharmacological doses of AASs, either alone or in conjunction with chronic exercise, induced changes in HSP72. Nandrolone decanoate (ND), an estrene derivative, but not stanozolol (ST), a derivative of the androstane series, up-regulated the levels of HSP72 and changed the proportions of various charge variants of the cytosolic HSP70s in sedentary and exercise-trained rats, exclusively in fast-twitch fibres. Since the expression of HSP73-levels in skeletal muscle was dependent on gender but not on muscle type, and that of HSP72-levels was muscle type specific but gender-independent, ND effects on cytosolic HSP70s could not be explained solely by a functional relationship with sex steroids. The reported results indicate that, by up-regulating the expression levels of HSP72 in fast-twitch fibres, nandrolone decanoate could contribute to improving the tolerance of skeletal muscle to high-intensity training.
Anabolic Agents↗
Secular trend and intrapopulational variation in age at menopause in Spanish women.
Menopause is associated with the general ageing process and marks the end of follicular depletion, a process that begins in the intrauterine stage and lasts throughout the lifetime of women until their reproductive senescence. Controversy persists about whether the age at menopause is sensitive to the ecological determinants prevailing during the lifecycle or whether it has a predominantly genetic component that would allow groups of women to be characterized with respect to particular menstrual characteristics manifested throughout their fertile life. By contrast, there is a definite secular trend in age at menarche in populations that have registered improvements in their environment: sexual maturation is closely associated with the general processes of growth and development. These aspects were analysed in a sample of Spanish women, mothers and daughters, born between 1883 and 1941. The results show (a) indications--although not conclusive--of a secular trend in the age at menopause, (b) a possible association between the age at menopause of mothers and their daughters, and (c) an association at the individual level between age at menarche, particular characteristics of ovarian function (fetal loss) and age at menopause. The reproductive ageing process therefore seems to result from the expression of the influence of ecological conditions in which the lifecycle of the women develops and of a degree of heritability that affects not only the age at menopause but also a range of characteristics of ovarian function.
Age Factors↗
Neuronal, astroglial and microglial cytokine expression after an excitotoxic lesion in the immature rat brain.
Cytokines are important intercellular messengers involved in neuron-glia interactions and in the microglial-astroglial crosstalk, modulating the glial response to brain injury and the lesion outcome. In this study, excitotoxic lesions were induced by the injection of N-methyl-D-aspartate in postnatal day 9 rats, and the cytokines interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), tumour necrosis factor alpha (TNFalpha) and transforming growth factor beta 1 (TGF-beta1) analysed by ELISA and/or immunohistochemistry. Moreover, cytokine-expressing glial cells were identified by means of double labelling with glial fibrillary acidic protein or tomato lectin binding. Our results show that both neurons and glia were capable of cytokine expression following different patterns in the excitotoxically damaged area vs. the nondegenerating surrounding grey matter (SGM). Excitotoxically damaged neurons showed upregulation of IL-6 and downregulation of TNFalpha and TGF-beta1 before they degenerated. Moreover, in the SGM, an increased expression of neuronal IL-6, TNFalpha and TGF-beta1 was observed. A subpopulation of microglial cells, located in the SGM and showing IL-1beta and TNFalpha expression, were the earliest glial cells producing cytokines, at 2-10 h postinjection. Later on, cytokine-positive glial cells were found within the excitotoxically damaged area and the adjacent white matter: some reactive astrocytes expressed TNFalpha and IL-6, and microglia/macrophages showed mild IL-1beta and TGF-beta1. Finally, the expression of all cytokines was observed in the glial scar. As discussed, this pattern of cytokine production suggests their implication in the evolution of excitotoxic neuronal damage and the associated glial response.
Age Factors↗