Showing papers by "University of Extremadura published in 2005"

Biodiesel from Used Frying Oil. Variables Affecting the Yields and Characteristics of the Biodiesel

Abstract: A study was performed of the transesterification reaction of used frying oil by means of methanol, using sodium hydroxide, potassium hydroxide, sodium methoxide, and potassium methoxide as catalysts. The objective of the work was to characterize the methyl esters for use as biodiesels in compression ignition motors. The operation variables used were methanol/oil molar ratio (3:1−9:1), catalyst concentration (0.1−1.5 wt %), temperature (25−65 °C), and catalyst type. Also, experiments in two stages of reaction, with separation of the glycerol in the first stage, were carried out. The evolution of the process was followed by gas chromatography, determining the concentration of the methyl esters at different reaction times. The biodiesel was characterized by its density, viscosity, high heating value, cetane index, cloud and pour points, characteristics of distillation, flash and combustion points, saponification value, and iodine value according to ISO norms. The biodiesel with the best properties was obtain...

Dimensionality reduction and classification of hyperspectral image data using sequences of extended morphological transformations

Abstract: This work describes sequences of extended morphological transformations for filtering and classification of high-dimensional remotely sensed hyperspectral datasets. The proposed approaches are based on the generalization of concepts from mathematical morphology theory to multichannel imagery. A new vector organization scheme is described, and fundamental morphological vector operations are defined by extension. Extended morphological transformations, characterized by simultaneously considering the spatial and spectral information contained in hyperspectral datasets, are applied to agricultural and urban classification problems where efficacy in discriminating between subtly different ground covers is required. The methods are tested using real hyperspectral imagery collected by the National Aeronautics and Space Administration Jet Propulsion Laboratory Airborne Visible-Infrared Imaging Spectrometer and the German Aerospace Agency Digital Airborne Imaging Spectrometer (DAIS 7915). Experimental results reveal that, by designing morphological filtering methods that take into account the complementary nature of spatial and spectral information in a simultaneous manner, it is possible to alleviate the problems related to each of them when taken separately.

Malarial parasites decrease reproductive success: an experimental study in a passerine bird

Abstract: Malarial parasites are supposed to have strong negative fitness consequences for their hosts, but relatively little evidence supports this claim due to the difficulty of experimentally testing this. We experimentally reduced levels of infection with the blood parasite Haemoproteus prognei in its host the house martin Delichon urbica, by randomly treating adults with primaquine or a control treatment. Treated birds had significantly fewer parasites than controls. The primaquine treatment increased clutch size by 18%; hatching was 39% higher and fledging 42% higher. There were no effects of treatment on quality of offspring, measured in terms of tarsus length, body mass, haematocrit or T-cell-mediated immune response. These findings demonstrate that malarial parasites can have dramatic effects on clutch size and other demographic variables, potentially influencing the evolution of clutch size, but also the population dynamics of heavily infected populations of birds.

Regeneration of a Mediterranean oak: A whole-cycle approach

Abstract: Using the holm oak (Quercus ilex) as a model system, we quantified the losses in the potential number of recruits from the flower to the sapling stage caused by abiotic factors, pre- and post-dispersal seed predators, and invertebrate and ungulate herbivores in one well-preserved forest plot (F) and in one dehesa (savanna-like) plot (D). Tree fecundity was an order of magnitude higher in D than in F. Predispersal (flower plus fruit) losses due to abiotic factors were much larger (71% in F and 90% in D) than those originated by biotic factors (29% in F and 10% in D). Post-dispersal predation of acorns under trees led to crop depletion in F, while predators did not deplete the acorn crop despite a much higher predation level in D. Surface acorns were invariably eaten, while most buried acorns survived to germination in both plots. Ninety-five percent of seedlings emerged under oaks in D and only 20% in F, the density of newly emerged seedlings being ten times greater in F. Emergence from experiment...

Arginase and polyamine synthesis are key factors in the regulation of experimental leishmaniasis in vivo.

Abstract: Arginase 1, an enzyme induced by Th2 cytokines, is a hallmark of alternatively activated macrophages and is responsible for the hydrolysis of L-arginine into ornithine, the building block for the production of polyamines. Upregulation of arginase 1 has been observed in a variety of diseases, but the mechanisms by which arginase contributes to pathology are not well understood. We reveal here a unique role for arginase 1 in the pathogenesis of nonhealing leishmaniasis, a prototype Th2 disease, and demonstrate that the activity of this enzyme promotes pathology and uncontrolled growth of Leishmania parasites in vivo. Inhibition of arginase activity during the course of infection has a clear therapeutic effect, as evidenced by markedly reduced pathology and efficient control of parasite replication. Despite the clear amelioration of the disease, this treatment does not alter the Th2 response. To address the underlying mechanisms, the arginase-induced L-arginine catabolism was investigated and the results demonstrate that arginase regulates parasite growth directly by affecting the polyamine synthesis in macrophages.

p38γ regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP

Abstract: Activation of the p38 MAP kinase pathways is crucial for the adaptation of mammalian cells to changes in the osmolarity of the environment. Here we identify SAP97/hDlg, the mammalian homologue of the Drosophila tumour suppressor Dlg, as a physiological substrate for the p38γ MAP kinase (SAPK3/p38γ) isoform. SAP97/hDlg is a scaffold protein that forms multiprotein complexes with a variety of proteins and is targeted to the cytoskeleton by its association with the protein guanylate kinase-associated protein (GKAP). The SAPK3/p38γ-catalysed phosphorylation of SAP97/hDlg triggers its dissociation from GKAP and therefore releases it from the cytoskeleton. This is likely to regulate the integrity of intercellular–junctional complexes, and cell shape and volume in response to osmotic stress.

How close are the phrenic nerves to cardiac structures? Implications for cardiac interventionalists.

Abstract: Phrenic Nerves and Cardiac Structures. Background: Phrenic nerve injury is a recognized complication following cardiac intervention or surgery. With increasing use of transcatheter procedures to treat drug-refractory arrhythmias, clarification of the spatial relationships between the phrenic nerves and important cardiac structures is essential to reduce risks. Methods and Results: We examined by gross dissection the courses of the right and left phrenic nerves in 19 cadavers. Measurements were made of the minimal and maximal distances of the nerves to the superior caval vein, superior cavoatrial junction, right pulmonary veins, and coronary veins. Histologic studies were carried out on tissues from six cavaders. Tracing the course of the right phrenic nerve revealed its close proximity to the superior caval vein (minimum 0.3 ′ 0.5 mm) and the right superior pulmonary vein (minimum 2.1 ′ 0.4 mm). The anterior wall of the right superior pulmonary vein was <2 mm from the right phrenic nerve in 32% of specimens. The left phrenic nerve passed over the obtuse cardiac margin and the left obtuse marginal vein and artery in 79% of specimens. In the remaining specimens, its course was anterosuperior, passing over the main stem of the left coronary artery or the anterior descending artery and great cardiac vein. Conclusions: The right phrenic nerve is at risk when ablations are carried out in the superior caval vein and the right superior pulmonary vein. The left phrenic nerve is vulnerable during lead implantation into the great cardiac and left obtuse marginal veins.

Resveratrol-induced apoptosis in MCF-7 human breast cancer cells involves a caspase-independent mechanism with downregulation of Bcl-2 and NF-kappaB.

Abstract: Resveratrol (RES), a chemopreventive molecule, inhibits the proliferation of tumor cells of different etiologies. We previously showed that RES alters the cell cycle and induces apoptosis in MCF-7 breast tumor cells by interfering with the estrogen receptor (ERaalpha)-dependent phosphoinositide 3-kinase (PI3K) pathway. Here, we analyzed signaling downstream of PI3K, to understand the mechanisms of RES-induced apoptosis. Apoptotic death by RES in MCF-7 was mediated by Bcl-2 downregulation since overexpression of this protein abolished apoptosis. Decreased Bcl-2 levels were not related to cytochrome c release, activation of caspases 3/8 or poly(ADP-ribose) polymerase proteolysis. However, RES decreased mitochondrial membrane potential and increased reactive oxygen species and nitric oxide production. NF-kappaB, a regulator of Bcl-2 expression, and calpain protease activity, a regulator of NF-kappaB, were both inhibited by RES. The patterns for NF-kappaB and calpain activities followed that of PI3K and were inhibited by LY294002. NF-kappaB inhibition coincided with diminished MMP-9 activity and cell migration. These data suggest that RES-induced apoptosis in MCF-7 could involve an oxidative, caspase-independent mechanism, whereby inhibition of PI3K signaling converges to Bcl-2 through NF-kappaB and calpain protease activity. Therefore, Bcl-2 and NF-kappaB could be considered potential targets for the chemopreventive activity of RES in estrogen-responsive tumor cells.

Protein Oxidation in Frankfurters with Increasing Levels of Added Rosemary Essential Oil: Effect on Color and Texture Deterioration

Abstract: The development of protein oxidation as assessed by the total carbonyl content and its influence on color and texture deterioration during the refrigerated storage (+4 °C/60 d) of frankfurters, were studied. The effect of the addition of a rosemary essential oil at different levels (150, 300, and 600 ppm) on the protein oxidative stability of the frankfurters was also evaluated. Frankfurters with no added essential oil were used as controls. The amount of carbonyls from protein oxidation significantly increased during refrigerated storage, and this increase was significantly higher in control frankfurters than in those treated with 300 and 600 ppm. Rosemary essential oil at levels of 300 and 600 ppm successfully protected the heme molecule from degradation and significantly inhibited the increase of nonheme iron (NHI) in refrigerated stored frankfurters. Color changes were directly related to oxidation processes because frankfurters with added antioxidants (300 and 600 ppm) suffered less color modifications than the controls. The addition of rosemary essential oil enhanced texture characteristics of frankfurters by reducing hardness, adhesiveness, gumminess, chewiness, and controlling the lost of elasticity during refrigeration. Statistically significant correlations were calculated between protein oxidation and instrumentally measured parameters, suggesting that the alteration of protein functionality caused by oxidation likely affected color and texture characteristics of frankfurters.

Sinus node revisited in the era of electroanatomical mapping and catheter ablation

Abstract: Objective: To study the architecture of the human sinus node to facilitate understanding of mapping and ablative procedures in its vicinity Methods: The sinoatrial region was examined in 47 randomly selected adult human hearts by histological analysis and scanning electron microscopy Results: The sinus node, crescent-like in shape, and 135 (25) mm long, was not insulated by a sheath of fibrous tissue Its margins were irregular, with multiple radiations interdigitating with ordinary atrial myocardium The distances from the node to endocardium and epicardium were variable In 72% of the hearts, the whole nodal body was subepicardial and in 13 specimens (28%) the inner aspect of the nodal body was subendocardial The nodal body cranial to the sinus nodal artery was more subendocardial than the remaining nodal portion, which was separated from the endocardium by the terminal crest In 50% of hearts, the most caudal boundaries of the body of the node were at least 35 mm from the endocardium When the terminal crest was > 7 mm thick (13 hearts, 28%), the tail was subepicardial or intramyocardial and at least 3 mm from the endocardium Conclusions: The length of the node, the absence of an insulating sheath, the presence of nodal radiations, and caudal fragments offer a potential for multiple breakthroughs of the nodal wavefront The very extensive location of the nodal tissue, the cooling effect of the nodal artery, and the interposing thick terminal crest caudal to this artery have implications for nodal ablation or modification with endocardial catheter techniques

Climatological Features of Cutoff Low Systems in the Northern Hemisphere

Abstract: This study presents the first multidecadal climatology of cutoff low systems in the Northern Hemisphere. The climatology was constructed by using 41 yr (1958-98) of NCEP-NCAR reanalysis data and identifying cutoff lows by means of an objective method based on imposing the three main physical characteristics of the conceptual model of cutoff low (the 200-hPa geopotential minimum, cutoff circulation, and the specific structure of both equivalent thickness and thermal front parameter fields). Several results were confirmed and climatologically validated: 1) the existence of three preferred areas of cutoff low occurrence (the first one extends through southern Europe and the eastern Atlantic coast, the second one is the eastern North Pacific, and the third one is the northern China-Siberian region extending to the northwestern Pacific coast; the European area is the most favored region); 2) the known seasonal cycle, with cutoff lows forming much more frequently in summer than in winter; 3) the short lifetime of cutoff lows, most cutoff lows lasted 2-3 days and very few lasted more than 5 days; and 4) the mobility of the system, with few cutoff lows being stationary. Furthermore, the long study period has made it possible (i) to find a bimodal distribution in the geographical density of cutoff lows for the European sector in all the seasons (with the exception of winter), a summer displacement to the ocean in the American region, and a summer extension to the continent in the Asian region, and (ii) to detect northward and westward motion especially in the transitions from the second to third day of occurrence and from the third to fourth day of occurrence. The long-term cutoff low database built in this study is appropriate to study the interannual variability of cutoff low occurrence and the links between cutoff lows and jet stream systems, blocking, or major modes of climate variability as well as the global importance of cutoff low in the stratosphere-troposphere exchange mechanism, which will be the focus of a subsequent paper.

The anatomical arrangement of the myocardial cells making up the ventricular mass.

Abstract: The architectural arrangement of the myocytes within the ventricular mass remains a highly contentious topic. It has recently been suggested by several distinguished surgeons that the overall myocardial structure is disposed in the form of a 'ventricular myocardial band'. There are, however, major anatomic deficiencies in this hypothesis, because the heart is formed on the basis of a modified blood vessel, rather than a collection of discrete muscular entities resembling the skeletal musculature. There is ample alternative evidence, nonetheless, already existing to provide a suitable explanation for the 'forceful reciprocal twisting' of the ventricular mass that is seen by cardiac surgeons during operative procedures. We provide here, therefore, a review of the anatomical studies we have performed separately and conjointly over a period of nearly 30 years. As before, we show that there is no anatomic evidence to support the concept of the 'ventricular myocardial band'. The overall arrangement is for the myocytes to be supported as the muscular components of a continuous and complex mass, the supporting collagenous fibrous matrix possessing epimysial, perimysial, and endomysial components. It had already been discussed at length during the previous century why there was no anatomic evidence to support the existence of separate 'muscles' within the ventricular continuum. There are no fibrous sheaths within the ventricular walls that permit the myofibres to be dissected on the basis of muscle bundles having a discrete origin and insertion, as is the case with the arrangement of the skeletal muscles. We have never sought ourselves, however, to deny the central helical nature of the overall architecture of the ventricular walls. The anatomic evidence supporting an overall helical nature for the ventricular myocardium has existed for over 150 years. All the available evidence, nonetheless, shows that these helical patterns are to be found throughout the walls, and in no way constitute a unique myocardial band.

Arginase I induction during Leishmania major infection mediates the development of disease.

Abstract: In a previous work, we demonstrated that the induction of arginase I favored the replication of Leishmania inside macrophages. Now we have analyzed the differential expression of this enzyme in the mouse model of L. major infection. Ours results show that arginase I is induced in both susceptible and resistant mice during the development of the disease. However, in BALB/c-infected tissues, the induction of this protein parallels the time of infection, while in C57BL/6 mice, the enzyme is upregulated only during footpad swelling. The induction of the host arginase in both strains is mediated by the balance between interleukin-4 (IL-4) and IL-12 and opposite to nitric oxide synthase II expression. Moreover, inhibition of arginase reduces the number of parasites and delays disease outcome in BALB/c mice, while treatment with l-ornithine increases the susceptibility of C57BL/6 mice. Therefore, arginase I induction could be considered a marker of disease in leishmaniasis.

Identification of sperm morphometric subpopulations in two different portions of the boar ejaculate and its relation to postthaw quality.

Abstract: A statistical approach using sequentially principal component analysis (PCA), clustering, and discriminant analyses was developed to identify sperm morphometric subpopulations in well-defined portions of the fresh boar ejaculate. Semen was obtained as 2 portions (the first 10 mL of the sperm-rich fraction and the rest of the ejaculate, respectively) and frozen using a conventional protocol. Before freezing, an aliquot was used for computer-assisted sperm morphometry analysis (ASMA). Postthaw quality was evaluated using computer-assisted sperm analysis (CASA), and an annexin-V/PI assay evaluated sperm membranes. The PCA revealed that 3 variables represented more than 78% of the cumulative variance in sperm subpopulations. The clustering and discriminant analyses, based on 5780 individual spermatozoa, revealed the existence of 4 sperm subpopulations. The relative percentage of these subpopulations varied between boar and ejaculate portions. Linear regression models based on measured morphometric characteristics could account for up to 36% of the percentage of intact sperm membranes postthaw. The ASMA protocol used in our study was useful to detect subtle morphometric differences between spermatozoa, and the combination of this analysis with a multivariate statistical procedure gave new information on the biological characteristics of boar ejaculates that is not given by conventional sperm analysis.

Bacterial degradation of cyanide and its metal complexes under alkaline conditions.

Abstract: A bacterial strain able to use cyanide as the sole nitrogen source under alkaline conditions has been isolated. The bacterium was classified as Pseudomonas pseudoalcaligenes by comparison of its 16S RNA gene sequence to those of existing strains and deposited in the Coleccion Espanola de Cultivos Tipo (Spanish Type Culture Collection) as strain CECT5344. Cyanide consumption is an assimilative process, since (i) bacterial growth was concomitant and proportional to cyanide degradation and (ii) the bacterium stoichiometrically converted cyanide into ammonium in the presence of l-methionine-d,l-sulfoximine, a glutamine synthetase inhibitor. The bacterium was able to grow in alkaline media, up to an initial pH of 11.5, and tolerated free cyanide in concentrations of up to 30 mM, which makes it a good candidate for the biological treatment of cyanide-contaminated residues. Both acetate and d,l-malate were suitable carbon sources for cyanotrophic growth, but no growth was detected in media with cyanide as the sole carbon source. In addition to cyanide, P. pseudoalcaligenes CECT5344 used other nitrogen sources, namely ammonium, nitrate, cyanate, cyanoacetamide, nitroferricyanide (nitroprusside), and a variety of cyanide-metal complexes. Cyanide and ammonium were assimilated simultaneously, whereas cyanide strongly inhibited nitrate and nitrite assimilation. Cyanase activity was induced during growth with cyanide or cyanate, but not with ammonium or nitrate as the nitrogen source. This result suggests that cyanate could be an intermediate in the cyanide degradation pathway, but alternative routes cannot be excluded.

A Family of Symmetric Distributions on the Circle

Abstract: We propose a new family of symmetric unimodal distributions on the circle that contains the uniform, von Mises, cardioid, and wrapped Cauchy distributions, among others, as special cases. The basic form of the densities of this family is very simple, although its normalization constant involves an associated Legendre function. The family of distributions can also be derived by conditioning and projecting certain bivariate spherically and elliptically symmetric distributions on to the circle. Trigonometric moments are available, and a measure of variation is discussed. Aspects of maximum likelihood estimation are considered, and likelihood is used to fit the family of distributions to an example set of data. Finally, extension to a family of rotationally symmetric distributions on the sphere is briefly made.

Pharmacogenomics education: International Society of Pharmacogenomics recommendations for medical, pharmaceutical, and health schools deans of education.

Abstract: Pharmacogenomics would be instrumental for the realization of personalized medicine in coming decades. Efforts are evident to clarify the potential bioethical, societal, and legal implications of key pharmacogenomics-based technologies projected to be soon introduced into the core practice of medicine. In sharp contrast, a lack of sufficient attention to educational aspects of pharmacogenomics, both for professionals and for society at large, is evident. In order to contribute to this discussion, a 'Pharmacogenomics Education Forum' was held on October 2, 2004 during the 3rd Annual Meeting of the International Society of Pharmacogenomics (ISP) at Santorini, Greece. The participants, members of the ISP Pharmacogenomics Education Forum, after deliberate discussions, proposed a document of 'Background Statement' and 'Recommendations and Call for Action' addressed to Deans of Education at Medical, Pharmaceutical, and Health Schools globally. This document has been considered by the education committee of the International Society of Pharmacogenomics and the result is presented here. We hope that this call would be listened to, and soon followed by beneficial action, ultimately leading to enhanced implementation of personalized medicine into core medical education and practice.

Necessity of methodologies to model rich Internet applications

Abstract: Several methodologies and tools have been proposed for Web applications design and development. However, traditional Web applications are still inadequate to support the interaction and presentation functionalities demanded by the users. Recently, rich Internet applications (RIAs) have been proposed as an answer to these problems providing new levels of interactivity and presentation. The use of RIAs is growing exponentially; nevertheless there is a lack of full development methodologies in this sense. This document outlines the main features, which should be modeled in RIAs and proposes an evaluation process in order to obtain the suitability of a methodology to accomplish this goal. We also use this process to evaluate the suitability of several existing Web, multimedia and hypermedia methodologies to demonstrate that each one accomplishes only few RIA features, so new methodologies or extensions of the actual methodologies become necessary.

Ca2+ accumulation into acidic organelles mediated by Ca2+- and vacuolar H+-ATPases in human platelets

Abstract: Most physiological agonists increase cytosolic free [Ca2+]c (cytosolic free Ca2+ concentration) to regulate a variety of cellular processes. How different stimuli evoke distinct spatiotemporal Ca2+ responses remains unclear, and the presence of separate intracellular Ca2+ stores might be of great functional relevance. Ca2+ accumulation into intracellular compartments mainly depends on the activity of Ca2+- and H+-ATPases. Platelets present two separate Ca2+ stores differentiated by the distinct sensitivity to thapsigargin and TBHQ [2,5-di-(t-butyl)-1,4-hydroquinone]. Although one store has long been identified as the dense tubular system, the nature of the TBHQ-sensitive store remains uncertain. Treatment of platelets with GPN (glycylphenylalanine-2-naphthylamide) impaired Ca2+ release by TBHQ and reduced that evoked by thrombin. In contrast, GPN did not modify Ca2+ mobilization stimulated by ADP or AVP ([arginine]vasopressin). Treatment with nigericin, a proton carrier, and bafilomycin A1, an inhibitor of the vacuolar H+-ATPase, to dissipate the proton gradient into acidic organelles induces a transient increase in [Ca2+]c that was abolished by previous treatment with the SERCA (sarcoplasmic/endoplasmic-reticulum Ca2+-ATPase) 3 inhibitor TBHQ. Depleted acidic stores after nigericin or bafilomycin A1 were refilled by SERCA 3. Thrombin, but not ADP or AVP, reduces the rise in [Ca2+]c evoked by nigericin and bafilomycin A1. Our results indicate that the TBHQ-sensitive store in human platelets is an acidic organelle whose Ca2+ accumulation is regulated by both Ca2+- and vacuolar H+-ATPases.

The Inferior Right Atrial Isthmus: Further Architectural Insights for Current and Coming Ablation Technologies

Abstract: Morphology and Structure of the Inferior Right Atrial Isthmus. Background: Although linear ablation of the right atrial isthmus in patients with isthmus-dependent atrial flutter can be highly successful, recurrences and complications occur in some patients. Our study provides further morphological details for a better understanding of the structure of the isthmus. Methods and Results: We examined the isthmic area in 30 heart specimens by dissection, histology, and scanning electron microscopy. This area was bordered anteriorly by the hinge of the tricuspid valve and posteriorly by the orifice of the inferior caval vein. With the heart in attitudinal orientation, we identified and measured the lengths of three levels of isthmus: paraseptal (24 ′ 4 mm), central (19 ′ 4 mm), and inferolateral (30 ′ 3 mm). Comparing the three levels, the central isthmus had the thinnest muscular wall and the paraseptal isthmus the thickest wall. At all three levels, the anterior part was consistently muscular whereas the posterior part was composed of mainly fibro-fatty tissue in 63% of hearts. The right coronary artery was less than 4 mm from the endocardial surface of the inferolateral isthmus in 47% of hearts. Inferior extensions of the atrioventricular node were present in the paraseptal isthmus in 10% of hearts, at 1-3 mm from the endocardial surface. Conclusions: The thinner wall and shorter length of the central isthmus together with its distance from the right coronary artery, and nonassociation with the atrioventricular node or its arterial supply, should make it the preferred site for linear radiofrequency ablation.

The effect of the cytochrome P450 CYP2C8 polymorphism on the disposition of (R)‐ibuprofen enantiomer in healthy subjects

Abstract: Aims To study the effect of CYP2C8*3, the most common CYP2C8 variant allele on the dis-position of (R)-ibuprofen and the association of CYP2C8*3 with variant CYP2C9 alleles. Methods Three hundred and fifty-five randomly selected Spanish Caucasians were screened for the common CYP2C8 and CYP2C9 mutations. The pharmacokinetics of (R)-ibuprofen were studied in 25 individuals grouped into different CYP2C8 genotypes. Results The allele frequency of CYP2C8*3 (0.17) was found to be higher than that reported for other Caucasian populations (P = 0.0001). The frequencies of CYP2C9*2 and CYP2C9*3 were 0.19 (0.16–0.21) and 0.10 (0.08–0.12), respectively. An association between CYP2C8*3 and CYP2C9*2 alleles was observed, occurring together at a frequency 2.4-fold higher than expected for a random association of alleles (P = 0.0001). The presence of the CYP2C8*3 allele was found to influence the pharmacokinetics of (R)-ibuprofen in a gene–dose effect manner. Thus, after administration of 400 mg ibuprofen, the plasma half-life (95% confidence intervals) for individuals with genotypes CYP2C8*1/*1, CYP2C8*1/*3 and CYP2C8*3/*3, was 2.0 h (1.8–2.2), 4.2 h (1.9–6.5; P < 0.05) and 9.0 h (7.8–10.2; P < 0.002), respectively. A statistically significant trend with respect to the number of variant CYP2C8*3 alleles was also observed for the area under the concentration-time curve (P < 0.025), and drug clearance (P < 0.03). Conclusion Polymorphism of the CYP2C8 gene was found to be common, with nearly 30% of the population studied carrying the variant CYP2C8*3 allele. The presence of the latter caused a significant effect on the disposition of (R)-ibuprofen. This suggests that a substantial proportion of Caucasian subjects may show alterations in the disposition of drugs that are CYP2C8 substrates.