Showing papers by "University of Valencia published in 2002"
TL;DR: In patients with chronic hepatitis C, once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferonAlfa- 2b plus Ribavirin and produced significant improvements in the rate of sustained virologic response, as compared with interfer on alfa -2b plus ribvirin or pegin terferonalfa-3a alone.
Abstract: Background Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. Methods A total of 1121 patients were randomly assigned to treatment and received at least one dose of study medication, consisting of 180 μg of peginterferon alfa-2a once weekly plus daily ribavirin (1000 or 1200 mg, depending on body weight), weekly peginterferon alfa-2a plus daily placebo, or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks. Results A significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response (defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy) th...
6,523 citations
TL;DR: A conceptual model featuring its complex, multiple, relativistic and dynamic nature as a more comprehensive framework of destination image is proposed as an intradisciplinary marketing perspective.
1,574 citations
TL;DR: This work has identified adult brain regions harboring neural stem cells and their continual generation of new neurons throughout life, an important departure from traditional views of the germinal potential of the postnatal brain.
Abstract: Much excitement has been generated by the identification of adult brain regions harboring neural stem cells and their continual generation of new neurons throughout life. This is an important departure from traditional views of the germinal potential of the postnatal brain. However, a more profound
1,419 citations
TL;DR: It is shown that transit-amplifying C cells retain stem cell competence under the influence of growth factors and are 53-fold enriched for neurosphere generation.
1,066 citations
TL;DR: The understanding of the biochemical and genetic basis of resistance to Bt can help design appropriate management tactics to delay or reduce the evolution of resistance in insect populations.
Abstract: Bacillus thuringiensis (Bt) is a valuable source of insecticidal proteins for use in conventional sprayable formulations and in transgenic crops, and it is the most promising alternative to synthetic insecticides. However, evolution of resistance in insect populations is a serious threat to this technology. So far, only one insect species has evolved significant levels of resistance in the field, but laboratory selection experiments have shown the high potential of other species to evolve resistance against Bt. We have reviewed the current knowledge on the biochemical mechanisms and genetics of resistance to Bt products and insecticidal crystal proteins. The understanding of the biochemical and genetic basis of resistance to Bt can help design appropriate management tactics to delay or reduce the evolution of resistance in insect populations.
907 citations
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TL;DR: In this article, the authors construct a set of meta-estimates of the coefficient of years of schooling in an aggregate Cobb-Douglas production function and show that after correcting for measurement error bias, the value of this parameter is well above 0.50.
Abstract: We construct estimates of educational attainment for a sample of OECD countries using previously unexploited sources. We follow a heuristic approach to obtain plausible time profiles for attainment levels by removing sharp breaks in the data that seem to reflect changes in classification criteria. We then construct indicators of the information content of our series and a number of previously available data sets and examine their performance in several growth specifications. We find a clear positive correlation between data quality and the size and significance of human capital coefficients in growth regressions. Using an extension of the classical errors in variables model, we construct a set of metaestimates of the coefficient of years of schooling in an aggregate Cobb-Douglas production function. Our results suggest that, after correcting for measurement error bias, the value of this parameter is well above 0.50.
791 citations
TL;DR: The global electrophilicity power, ω, of a series of dienes and dienophiles commonly used in Diels-Alder reactions may be conveniently classified within a unique relative scale as discussed by the authors.
760 citations
TL;DR: In persons with type 1 diabetes, an increase in systolic blood pressure during sleep precedes the development of microalbuminuria, and in those whose blood Pressure during sleep decreases normally, the progression from normal albumin excretion to micro albuminuria appears to be less likely.
Abstract: Background Patients with type 1 diabetes mellitus and microalbuminuria often have elevated blood pressure while they are asleep, but it is not known whether the elevation develops concomitantly with microalbuminuria or precedes it. Methods We monitored 75 adolescents and young adults who had had type 1 diabetes with normal urinary albumin excretion and blood pressure for more than five years. Ambulatory blood-pressure monitoring was used to assess blood pressure at the initial evaluation and about two years later, at which time all subjects had normal urinary albumin excretion. Subsequently, subjects were monitored for the development of microalbuminuria. Results Microalbuminuria developed in 14 subjects, whereas the other 61 continued to have normal urinary albumin excretion. The mean (±SD) systolic pressure during sleep increased significantly in the subjects who ultimately had microalbuminuria (from 109.9±11.3 to 114.9±11.7 mm Hg, P=0.01) but not in the subjects with normal albumin excretion (from 106....
694 citations
TL;DR: In this paper, a trabajo analiza la eficiencia en costes and beneficios in una muestra de 11 paises de la Union Europea in el periodo 1993-93 by medio de diversas tecnicas frontera.
537 citations
TL;DR: There is growing evidence that nNOS biosynthesis in excitable tissues is not restricted to neurones while substantial amounts of this enzyme have been identified in skeletal muscle, where it is involved in the regulation of metabolism and muscle contractility.
Abstract: The discovery that nitric oxide (NO) functions as a signalling molecule in the nervous system has radically changed the concept of neural communication. Indeed, the adoption of the term nitrergic for nerves whose transmitter function depends on the release of NO or for transmission mechanisms brought about by NO (Moncada et al., 1997) emphasizes the specific characteristics of this mediator. The physical properties of NO prevent its storage in lipid-lined vesicles and metabolism by hydrolytic degradatory enzymes. Therefore, unlike established neurotransmitters, NO is synthesized on demand and is neither stored in synaptic vesicles nor released by exocytosis, but simply diffuses from nerve terminals. The distance of this NO diffusion (40 – 300 μm in diameter) implies that structures in the vicinity of the producing cell, both neuronal and non-neuronal, are influenced following its release. This suggests that, as well as acting as a neurotransmitter, NO has a neuromodulatory role (Garthwaite & Boulton, 1995). In addition, it diffuses into rather than binds with protein receptors on adjacent cells, and most of its known actions are the consequence of interplay with intracellular targets that would usually be regarded as secondary messengers. The activity of conventional neurotransmitters is terminated either by re-uptake mechanisms or enzymatic degradation while inactivation of NO follows reaction with a substrate. There are multiple points at which biological control can be exerted over the production and activity of conventional neurotransmitters. However, control of the synthesis of NO is the key to regulating its activity.
Endothelial NOS (eNOS) and inducible NOS (iNOS) are present in the nervous system and will be duly addressed here. However, neuronal NOS (nNOS) is the principal isoform present in said system and will be the main focus of this review. All nNOS positive neurones exhibit α-nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase activity, which has become the histochemical marker of nitrergic neurones. However, early results demonstrating this may have been limited by inappropriate fixation procedures and should be viewed with caution (Wolf, 1997). The original cloning of full-length nNOS produced what is now designated as nNOSα, and which accounts for the majority of nNOS activity in nervous tissue (Bredt et al., 1991). In addition, four splice variants have recently been identified (nNOSβ, nNOSγ, nNOSμ and nNOS-2) and these appear to exhibit distinct cellular and tissue locations (Gibson, 2001; Nakane et al., 1993; Silvagno et al., 1996; Alderton et al., 2001). In particular, there is growing evidence that nNOS biosynthesis in excitable tissues is not restricted to neurones while substantial amounts of this enzyme have been identified in skeletal muscle, where it is involved in the regulation of metabolism and muscle contractility (Stamler & Meissner, 2001).
The magnitude of literature dealing with the role of NO in the nervous system is so great that it would be impossible to include in this review the entirety of the research carried out. For logistical reasons, only groundbreaking references have been quoted, but when necessary, recent reviews dealing with specific areas within the field have been included and are intended to act as a guideline for further reading.
493 citations
TL;DR: It is demonstrated that stem cells are not confined to the forebrain periventricular region and indicate that stem Cells endowed with different functional characteristics occur at different levels of the SVZ–RE pathway.
Abstract: The lateral walls of the forebrain lateral ventricles are the richest source of stem cells in the adult mammalian brain. These stem cells give rise to new olfactory neurons that are renewed throughout life. The neurons originate in the subventricular zone (SVZ), migrate within the rostral extension (RE) of the SVZ along the rostral migratory stream (RMS) within tube-like structures formed of glial cells, to eventually reach the olfactory bulb (OB). We demonstrate that, contrary to the current view, multipotential (neuronal-astroglial-oligodendroglial) precursors with stem cell features can be isolated not only from the SVZ but also from the entire RE, including the distal portion within the OB. Specifically, these stem cells do not derive from the migratory neuroblasts coming from the SVZ. Interestingly, stem cells isolated from the proximal RE generate significantly more oligodendrocytes, and those from the distal RE proliferate significantly more slowly than stem cells derived from the SVZ and other RE regions. These findings demonstrate that stem cells are not confined to the forebrain periventricular region and indicate that stem cells endowed with different functional characteristics occur at different levels of the SVZ-RE pathway.
TL;DR: The results of the present work suggest that the anti-inflammatory activities of the same extracts could be explained, at least in part, by their antioxidant properties.
TL;DR: In this article, the mechanism of free radical formation in type 1 diabetes and its possible prevention was studied and an increase in plasma xanthine oxidase activity may be explained by the increase in hepatic release of this enzyme, which is not due to nonspecific membrane damage: release of other hepatic enzymes such as the amino transferases, does not increase in diabetes.
Abstract: The aim of this work was to study the mechanism of free radical formation in type 1 diabetes and its possible prevention. We have found oxidation of blood glutathione and an increase in plasma lipoperoxide levels in both human type 1 diabetes and experimental diabetes. Peroxide production by mitochondria does not increase in diabetes. On the contrary, the activity of xanthine oxidase, a superoxide-generating enzyme, increases in liver and plasma of diabetic animals. The increase in plasma xanthine oxidase activity may be explained by the increase in the hepatic release of this enzyme, which is not due to nonspecific membrane damage: release of other hepatic enzymes, such as the amino transferases, does not increase in diabetes. Superoxide formation by aortic rings of rabbits increases significantly in diabetes. This is completely inhibited by allopurinol, an inhibitor of xanthine oxidase. Heparin, which releases xanthine oxidase from the vessel wall, also decreases superoxide formation by aortic rings of diabetic animals. Treatment with allopurinol decreases oxidative stress in type 1 diabetic patients: hemoglobin glycation, glutathione oxidation, and the increase in lipid peroxidation are prevented. These results may have clinical significance in the prevention of late-onset vascular complications of diabetes.
TL;DR: A methodology for quantifying calcium carbonate and silica by FTIR spectroscopy applying the constant ratio method is proposed and the granulometric study suggests that the homogeneity of particle size is important.
TL;DR: This article provided new measures of human capital inequality for a broad panel of countries, taking attainment levels from Barro and Lee (2001) and compute Gini coefficients and the distribution of education by quintiles for 108 countries over five-year intervals from 1960 to 2000.
Abstract: This paper provides new measures of human capital inequality for a broad panel of countries. Taking attainment levels from Barro and Lee (2001), we compute Gini coefficients and the distribution of education by quintiles for 108 countries over five-year intervals from 1960 to 2000. Using this new cross-country data on human capital inequality two main conclusions are obtained. First, most countries in the world have tended to reduce the inequality in human capital distribution. Second, human capital inequality measures provide more robust results than income inequality measures in the estimation of standard growth and investment equations.
TL;DR: The antimetastatic mechanism involves a t-RES (1 microM)-induced inhibition of vascular adhesion molecule 1 (VCAM-1) expression in the hepatic sinusoidal endothelium (HSE), which consequently decreased in vitro B16M cell adhesion to the endothelia via very late activation antigen 4 (VLA-4).
01 Jan 2002
TL;DR: In this article, the authors investigate the influence of distintas dimensiones of the personalidad of a trabajador in the determinación of salarial salarios, e.g., empatia, extroversion, autonomia, and the estabilidad emocional.
Abstract: El objetivo de este trabajo es investigar sobre la influencia de distintas dimensiones de la personalidad del individuo en la determinacion salarial. El estudio esta inspirado en Bowles, Gintis y Osborne (2001) que propone una base teorica para la idea de que algunas caracteristicas de la personalidad de los trabajadores podrian ser recompensadas (o penalizadas) en el mercado laboral. Para contrastar esta idea utilizamos datos del CentER Saving Survey, un panel de datos representativo de la poblacion holandesa que ofrece informacion sobre la personalidad. Concretamente inclyue el Five-Factor-Personality-Inventory que mide la diligencia, empatia, extroversion, autonomia y la estabilidad emocional del individuo, consideradas las cinco grandes dimensiones de la personalidad. En el analisis empirico se tienen en cuenta las diferencias por genero y la endogeneidad entre personalidad y salarios. Las estimaciones de la ecuacion de salarios muestran que, para los hombres, la empatia tiene un efecto negativo en los salarios mientras que, para las mujeres, la estabilidad emocional afecta positivamente. La contribucion de estas variables a la varianza explicada implica que la personalidad explica una porcion adicional de la varianza de los salarios independientemente de las variables tradicionales de capital humano, especialmente en el caso de las mujeres.
TL;DR: In this paper, the authors described the local electrophilicity at the active sites of the reagents involved in polar Diels−Alder processes using an extension of the global electrophilic inde...
Abstract: Regional electrophilicity at the active sites of the reagents involved in polar Diels−Alder processes may be described on a quantitative basis using an extension of the global electrophilicity inde...
TL;DR: In this article, a transfer function intervention model is developed for forecasting daily electricity load from cooling and heating degree-days in Spain, and the influence of weather and seasonality is proved, and is significant even when the autoregressive effects and the dynamic specification of the temperature are taken into account.
TL;DR: The results establish the molecular etiology of CMT4A (MIM 214400) and suggest that it may be associated with both axonal and demyelinating phenotypes.
Abstract: We identified three distinct mutations and six mutant alleles in GDAP1 in three families with axonal Charcot-Marie-Tooth (CMT) neuropathy and vocal cord paresis, which were previously linked to the CMT4A locus on chromosome 8q21.1. These results establish the molecular etiology of CMT4A (MIM 214400) and suggest that it may be associated with both axonal and demyelinating phenotypes.
Abstract: GroEL, a heat-shock protein that acts as a molecular chaperone1, is overproduced in endosymbiotic but not in free-living bacteria2,3,4, presumably to assist in the folding of conformationally damaged proteins. Here we show that the overproduction of GroEL in Escherichia coli masks the effects of harmful mutations that have accumulated during a simulated process of vertical transmission. This molecular mechanism, which may be an adaptation to the bacterium's intracellular lifestyle, is able to rescue lineages from a progressive fitness decline resulting from the fixation of deleterious mutations under strong genetic drift5,6.
TL;DR: In this article, a generalized soil adjusted vegetation index (GESAVI) is introduced, which is defined in terms of the soil line parameters (A and B) as: GESAVI=(NIRBRA)/(R+Z), where Z is related to the red reflectance at the cross point between the soil lines and vegetation isolines.
TL;DR: It is found that the SSU1-R allele, which confers sulfite resistance to yeast cells, is the product of a reciprocal translocation between chromosomes VIII and XVI due to unequal crossing-over mediated by microhomology between very short sequences on the 5' upstream regions of theSSU1 and ECM34 genes.
Abstract: The unaware use of yeast for winemaking by the first agricultural civilizations has been reported as far back as 7400 years ago. Until the middle of the last millennium, wines were mainly produced around the Mediterranean Sea and the Caucasus. Since then, winemaking has spread with the European colonizers throughout the temperate regions of the world (Pretorius 2000).
Although different genera and species of yeasts are found in musts, the species Saccharomyces cerevisiae is mainly responsible for the transformation of musts into wines. The origin of S. cerevisiae is controversial. Some authors propose that this species is a “natural” organism present in plant fruits (Mortimer and Polsinelli 1999). Others argue that S. cerevisiae is a domesticated species originated from its closest relative S. paradoxus, a wild species found all around the world (Vaughan-Martini and Martini 1995). This debate is important in postulating the original genome of S. cerevisiae and how the strong selective pressure applied since its first unconscious use in controlled fermentation processes has reshaped it. Useful phenotypic traits such as fast growth in sugar-rich media, high alcohol production and tolerance, and good flavor production selected for billions of generations have had strong influences on the S. cerevisiae genome.
In contrast to most S. cerevisiae strains used in the laboratory, which are either haploid or diploid and have a constant chromosome electrophoretic profile, wine yeast strains are mainly diploid, aneuploid, or polyploid, homothallic, and highly heterozygous (Bakalinsky and Snow 1990; Barre et al. 1993; Codon et al. 1995), and show a high level of chromosome length polymorphisms (Bidenne et al. 1992; Rachidi et al. 1999). Moreover, wine yeast strains seem not to remain genetically uniform (Pretorius 2000). Their exacerbated capacity to reorganize its genome by chromosome rearrangements such as Ty-promoted chromosomal translocations (Longo and Vezinhet 1993; Rachidi et al. 1999), mitotic crossing-over (Aguilera et al. 2000), and gene conversion (Puig et al. 2000) promotes a faster adaptation to environmental changes than spontaneous mutations, which occur at comparatively very low rates. The ploidy of the wine yeasts may confer advantages in adapting to variable external environments or increasing the dosage of some genes important for fermentation (Bakalinsky and Snow 1990; Salmon 1997).
In addition, the possibility of adaptive gross genomic changes occurring during laboratory growth conditions has been demonstrated with DNA chip technology by Hughes et al. (2000). Those authors showed in multiple cases that the deletion of a gene strongly favors the acquisition of a second copy of a whole chromosome or a chromosomal segment containing a compensatory copy of a close homolog of the deleted gene.
In a comparative study of transcriptomes, we found that SSU1, a gene that mediates sulfite efflux in S. cerevisiae and, hence, confers sulfite resistance (Park and Bakalinsky 2000), showed a significantly higher expression in the T73 wine yeast strain than in a laboratory strain (Hauser et al. 2001). In contrast to the allele present in the laboratory strains, a highly sulfite-resistant wine strain exhibited a translocation involving the promoter region of the gene (SSU1-R allele), which produces an increase in the sulfite resistance (Goto-Yamamoto et al. 1998). In the present study, we explored the organization of this gene at the molecular level in different wine yeast strains.
TL;DR: The hypothesis that a Mediterranean diet that emphasizes olive oil, fiber, fruits, vegetables, fish and alcohol and reduces meat/meat products can be an effective measure for reducing the risk of myocardial infarction is supported.
Abstract: Background: Although an important secondary prevention trial reported an impressive protection by a Mediterranean dietary pattern on reinfarction and cardiovascular death, scarce direct epidemiologic evidence is currently available regarding the role of the Mediterranean diet in the aetiology of coronary heart disease. Aims: The aim of the study was to quantify the risk reduction of incident myocardial infarction provided by a Mediterranean dietary pattern. Methods: We included 342 subjects (171 patients who suffered their first acute myocardial infarction and 171 matched controls) in a case-control study. A validated semi-quantitative food frequency questionnaire (136 items) was used. We defined an a priori Mediterranean dietary pattern. We assessed six food items that we considered protective: 1) olive oil, 2) fiber, 3) fruits, 4)vegetables, 5) fish and 6) alcohol. For each of these six dietary factors, we calculated the distribution according to quintiles within the study and assigned each participant a score of 1 to 5 corresponding to the quintile of intake, with 1 representing the lowest and 5 representing the highest quintile. We also estimated the quintiles of two other elements assumed to be associated with a higher risk: 7) meat/meat products and 8) some items with high glycaemic load (white bread, pasta and rice). For these two elements we inversely ranked the score, with 1 representing the highest and 5 representing the lowest quintile. Finally, we summed up the eight quintile values for each participant. A second score (post hoc pattern) was built using only a single cut-off point for these eight elements. The cut-off points for each element in this post hoc pattern were decided according to the dose-response relationships between the consumption of each food item and the risk of myocardial infarction observed in the analyses that used quintiles of each food item. Results: For both patterns, we found that the higher the score, the lower the odds ratio of myocardial infarction. A significant linear trend was apparent after adjustment for the main cardiovascular risk factors. For each additional point in the a priori Mediterranean pattern (observed range: 9–38) the odds ratio (95 % confidence intervals) was 0.92 (0.86–0.98). This estimate was 0.55 (0.42–0.73) when we used the post hoc pattern (range: 0–8). Conclusions: Our data support the hypothesis that a Mediterranean diet (that emphasizes olive oil, fiber, fruits, vegetables, fish and alcohol and reduces meat/meat products) can be an effective measure for reducing the risk of myocardial infarction. However, our results support the exclusion of refined cereals with a high glycaemic load as healthy elements of this pattern.
TL;DR: The high variety of debris found and the large differences in ingestion among turtles indicated low feeding discrimination of this species that makes it specially prone to debris ingestion, which suggests that more severe control of litter spills and greater promotion of environmental educational programmes are needed in the Western Mediterranean.
TL;DR: Evidence is shown of six species with a genome size smaller than Mycoplasma genitalium, the smallest bacterial genome reported thus far, which strongly suggest that the Buchnera genome is still experiencing a reductive process toward a minimum set of genes necessary for its symbiotic lifestyle.
Abstract: Buchnera is a mutualistic intracellular symbiont of aphids. Their association began about 200 million years ago, with host and symbiont lineages evolving in parallel since that time. During this coevolutionary process, Buchnera has experienced a dramatic decrease of genome size, retaining only essential genes for its specialized lifestyle. Previous studies reported that genome size in Buchnera spp. is very uniform, suggesting that genome shrinkage occurred early in evolution, and that modern lineages retain the genome size of a common ancestor. Our physical mapping of Buchnera genomes obtained from five aphid lineages shows that the genome size is not conserved among them, but has been reduced down to 450 kb in some species. Here we show evidence of six species with a genome size smaller than Mycoplasma genitalium, the smallest bacterial genome reported thus far (580 kb). Our findings strongly suggest that the Buchnera genome is still experiencing a reductive process toward a minimum set of genes necessary for its symbiotic lifestyle.
TL;DR: In this article, the authors examined the relationships between individual psychological, work environment and organizational variables and occupational accidents using structural equation modelling with latent variables and found that individual safe behaviour is strongly predicted within the model, although it is mainly related to organizational involvement in safety and not directly to perceptions of the physical work environment.
Abstract: This study examined the relationships between individual psychological, work environment and organizational variables and occupational accidents using structural equation modelling with latent variables. A series of nested explicative models of the relationships between these variables was derived. Data were collected from a wide range of industrial sectors in the Valencia region of Spain using structured interviews. In total, 525 valid questionnaires were completed and these formed the basis for the subsequent analyses. Analysis showed that the model in the series that proposed relationships between all the latent variables provided the best representation of the data. This supported the broad hypothesis that each of the variables has an effect on accidents and also showed that the individual level variables, including safe behaviour and general heath, mediate the indirect effects from the organizational variables. The final model showed that individual safe behaviour is strongly predicted within the model, although it is mainly related to organizational involvement in safety and not directly to perceptions of the physical work environment. An important role is played in the final model by participants' evaluations of organizational involvement in safety and this is consistent with earlier work highlighting the importance of management commitment to, and action on, safety issues. Finally, the model supported the proposal that stress processes mediate the effects of both organizational and environmental variables.
TL;DR: The results support the idea that IL‐6 down‐regulates CYP3A4 through translational induction of C/EBPβ‐LIP, which competes with and antagonizes constitutive C/ EBP transactivators, and could be relevant in the development of therapeutic cytokines with a less repressive effect on hepatic drug‐metabolizing enzymes.
Abstract: The hepatic drug-metabolizing cytochrome P-450 (CYP) enzymes are down-regulated during inflammation. In vitro studies with hepatocytes have shown that the cytokines released during inflammatory responses are largely responsible for this CYP repression. However, the signaling pathways and the cytokine-activated factors involved remain to be properly identified. Our research has focused on the negative regulation of CYP3A4 (the major drug-metabolizing human CYP) by interleukin 6 (IL-6) (the principal regulator of the hepatic acute-phase response). CYP3A4 down-regulation by IL-6 requires activation of the glycoprotein receptor gp130; however, it does not proceed through the JAK/STAT pathway, as demonstrated by the overexpression of a dominant-negative STAT3 factor by means of an adenoviral vector. The involvement of IL-6-activated kinases such as extracellular signal-regulated kinase ERK1/2 or p38 is also unlikely, as evidenced by the use of specific chemical inhibitors. It is noteworthy that IL-6 caused a moderated induction in the mRNA of the transcription factor C/EBPbeta (CCAAT-enhancer binding protein beta) and a marked increase in the translation of C/EBPbeta-LIP, a 20-kDa C/EBPbeta isoform lacking a transactivation domain. Adenovirus-mediated expression of C/EBPbeta-LIP caused a dose-dependent repression of CYP3A4 mRNA, whereas overexpression C/EBPalpha and C/EBPb-LAP (35 kDa) caused a significant induction. Our results support the idea that IL-6 down-regulates CYP3A4 through translational induction of C/EBPbeta-LIP, which competes with and antagonizes constitutive C/EBP transactivators. From a clinical point of view, these findings could be relevant in the development of therapeutic cytokines with a less repressive effect on hepatic drug-metabolizing enzymes.
TL;DR: In this article, the S-wave interaction of mesons with baryons in the strangeness S = 0 sector in a coupled channel unitary approach is studied and the basic dynamics are drawn from the lowest order meson baryon chiral Lagrangians.
Abstract: We study the S-wave interaction of mesons with baryons in the strangeness S=0 sector in a coupled channel unitary approach. The basic dynamics is drawn from the lowest order meson baryon chiral Lagrangians. Small modifications inspired by models with explicit vector meson exchange in the t-channel are also considered. In addition the pi pi N channel is included and shown to have an important repercussion in the results, particularly in the isospin 3/2 sector.