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Biomedical subjects

J Corbella

Publications and source records attributed to J Corbella.

At least 19 recordsLinked to original sources
PubMed2003

Polybrominated diphenyl ethers (PBDEs) in foodstuffs: human exposure through the diet.

Polybrominated diphenyl ethers (PBDEs) are used as flame retardants in a variety of materials, including synthetic polymers and textiles. Although these chemicals have been detected in environmental samples and human tissues, there is little information about human exposure to PBDEs through the diet. In the present study, we determined the concentrations of PBDEs in a number of food samples acquired in Catalonia (Spain) during 2000. The dietary intake of PBDEs was estimated for the general population living in this Spanish region. The highest PBDE concentrations were found in oils and fats, fish and shellfish, meat and meat products, and eggs, while the lowest levels corresponded to fruits, vegetables, and tubers. The dietary intake of PBDEs for an adult male was 97.3 ng/day (assuming not detected (ND) = (1)/(2) limit of detection (LOD)) or 81.9 ng/day (assuming ND = 0) The greatest contribution to these values corresponded to fish and shellfish, with approximately one-third of the total intake. TetraBDEs and pentaBDEs were the homologues showing the highest percentages of contribution to the sum of total PBDEs. The comparison of the current dietary intake with the suggested lowest observed adverse effect level value of 1 mg/kg/day for the most sensitive endpoints for toxic effects of PBDEs results in a safety factor over 5 orders of magnitude in relation to PBDE exposure from food.

Adult↗
PubMed2003

Pharmacokinetic and pharmacodynamic correlations of cyclosporine therapy in stable renal transplant patients: evaluation of long-term target C(2).

We investigated the relationship between the pharmacokinetics and pharmacodynamics of cyclosporine in 15 stable renal transplant patients in order to define an effective and safe therapeutic range. The area under the curve of the first 4 h (AUC(0-4)), trough (C(0)) and 2 h (C(2)) levels showed median values of 1655 ng x h/ml, 114 ng/ml and 384 ng/ml, respectively. C(2) showed a strong correlation with AUC(0-4) (r=0.942, p=0.0005). C(0) correlated poorly with C(2) and AUC(0-4) (r=0.596, p=0.019 and r=0.538, p=0.031, respectively). Calcineurine activity (CNa) was 6.74% at 0 h and 3.90% at 2 h, representing significant reductions (82% and 89.6%, respectively; p<0.0005) compared with normal healthy controls (median basal value 37.4%). IL-2 production was 349 pg/ml at 0 h and 276.35 pg/ml at 2 h; both results were significantly lower (reductions of 44.5% and 56.1%, respectively; p=0.04 and 0.005) than the controls of 629.1 pg/ml. IFN-gamma at 2 h post-dose (8.16 UI/ml) was significantly lower (72.1% reduction, p=0.005) than in controls (29.2 UI/ml). There was a good correlation between CNa and IFN-gamma production, particularly at 2 h post-dose (r=0.537, p=0.007), and a fair correlation between CNa and IL-2 concentration (p=0.030, r=0.426). C(2) showed an inverse significant correlation with CNa (Spearman's p=0.000, r=-0.753), IL-2 (p=0.000, r=-0.725) and IFN-gamma (p=0.000, r=-0.701) production. In treated patients, the Emax inhibitory sigmoidal model showed that a C(2) of 279 ng/ml was needed to achieve a 50% inhibition (EC50) of IL-2 and INF-gamma production. The results demonstrated a significant inhibition of calcineurin activity and IL-2 and IFN-gamma production in patients receiving cyclosporine monotherapy compared to healthy controls. A median C(2) value of 384 ng/ml was associated with a good degree of inhibition of CNa and IL-2 and IFN-gamma synthesis, and the lack of rejection episodes and relevant toxicity.

Area Under Curve↗
PubMed2002

Biological monitoring of environmental exposure to manganese in blood samples from residents of the city of Barcelona, Spain.

Serum manganese levels were determined in 250 healthy subjects (122 men and 128 women) living in Barcelona in northeastern Spain. The study was designed to assess the reference levels for serum manganese and to investigate its relationship to age and sex. The age distribution ranged from 15 to 90 years. The assays were performed by means of a graphite furnace atomic absorption spectrometry. The geometric mean of serum manganese concentration was 1.1 microg/l, ranging from 0.3 microg/l to 2.5 microg/l. In almost every case, the 95th upper percentiles of this element were < 1.8 microg/l. No correlation between the concentration of manganese and sex could be established, but in the younger population the manganese levels were nearly three times higher than the results obtained in the older population.

Adolescent↗
PubMed2002

Health risk assessment of PCDD/PCDF exposure for the population living in the vicinity of a municipal waste incinerator.

Emissions of polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) by municipal solid waste (MSW) incinerators cause concern to the populations living in the vicinity of these facilities. In this study, the health risks of PCDD/F exposure were assessed for adults and children living 500 and 1,000 m from the MSW incinerator. A comparative analysis was performed before (1998) and after (2000) pronounced decreases in PCDD/F air emissions from the stack were noted as a consequence of technical improvements in the facility. At 500 m, total environmental exposure to PCDD/Fs diminished from 5.102 x 10(-5) to 1.271 x 10(-5) ng I-TEQ/kg/day for adults, and from 8.131 x 10(-5) to 2.656 x 10(-5) ng I-TEQ/kg/day for children, which means a reduction of 75.1% for adults and 67.3% for children between 1998 and 2000. At 1,000 m, total environmental PCDD/F exposure diminished from 4.087 x 10(-5) ng I-TEQ/kg/day in 1998 to 0.995 x 10(-5) ng I-TEQ/kg/day in 2000 and from 6.294 x 10(-5) ng I-TEQ/kg/day in 1998 to 1.983 x 10(-5) ng I-TEQ/kg/day in 2000 for adults and children, respectively. However, these reductions are almost imperceptible compared with the contribution of dietary intake of PCDD/F to total exposure to these contaminants. The present results corroborate that for MSW incinerators with modern technologies, human PCDD/F exposure is mainly due to background contamination.

Adolescent↗
PubMed2002

Interactions in developmental toxicology: effects of concurrent exposure to lead, organic mercury, and arsenic in pregnant mice.

The development toxicity of lead nitrate (25 mg/kg, SC), methylmercury chloride (12.5 mg/kg, PO), and sodium arsenite (6 mg/kg, SC) was assessed in CD1 mice following administration on gestation day 10 of these chemicals separately or in their binary and ternary combinations. Cesarean sections were performed on day 18 of gestation, and fetuses were examined for malformations and variations. Three fetuses from each dam were used for whole-body analyses of Pb, Hg, and As. Maternal toxic effects were more remarkable in the group concurrently exposed to Pb, Hg, and As than in those given binary combinations of the elements. In turn, maternal toxicity was more notable in these groups than in those given separately the test compounds. With regard to developmental toxicity, the most relevant effects (decreased fetal weight, cleft palate) corresponded to the Hg-treated groups. It is in agreement with the finding that in all experimental groups the levels of Pb and As in whole fetuses were under their respective detection limits. In general terms, the present data suggests that at the current doses, the interactive effects of Pb and As on Hg-induced developmental toxicity were not greater than additive. In contrast, exposure of pregnant mice to Pb and As at doses that were practically nontoxic to dams, concurrently with organic Hg at a toxic dose, caused supra-additive interactions in maternal toxicity.

Administration, Oral↗
PubMed2001

Lung cancer susceptibility in relation to combined polymorphisms of microsomal epoxide hydrolase and glutathione S-transferase P1.

Human microsomal epoxide hydrolase (mEH) catalyzes a key step in the biotransformation of benzo[a]pyrene that yields the highly mutagenic (+)-anti-7,8-diol-9,10 epoxide (BPDE). Two polymorphisms have been described in the coding region of the mEH gene (EPHX1) that produce two protein variants: 113Tyr-->113His (exon 3) and 139His-->139Arg (exon 4). We performed a case-control study among Northwestern Mediterranean Caucasians to investigate a possible association between these EPHX1 variants and lung cancer risk. Both EPHX1 polymorphisms were analyzed in a group of lung cancer patients (n=176) and in a control group of healthy smokers (n=187). The results showed a significantly decreased risk for the rare homozygous 113His/113His (adjusted odds ratio (OR): 0.44, 95% confidence interval (CI): 0.27-0.71) and 139Arg/139Arg (adjusted OR: 0.55, 95% CI: 0.33-0.91) compared with the major wild-types 113Tyr/113Tyr and 139His/139His, respectively, as the references. Thereafter, we analyzed the EPHX1 variants in combination with three glutathione S-transferase polymorphic genes (GSTM1, GSTT1, and GSTP1) and we found a significant overepresentation of cancer patients with a combination of exon 3 113Tyr/113Tyr EPHX1 and exon 5 105Ile/105Ile GSTP1 (adjusted OR: 2.34, 95% CI: 1.21-4.52). The polymorphic site within the exon 5 of GSTP1 results in a Ile-->Val substitution, and the isoleucine GSTpi isoform has been found in vitro to be less active than the valine isoform towards the conjugation of BPDE. The 113 Tyr/Tyr EPHX1 encodes for a high-activity mEH. Our results agree with these observations in vitro and suggest that a genetically determined combination of a high-activity mEH and a low-activity GSTpi may increase lung cancer risk among smokers.

Adult↗
PubMed2001

The Bubi population of Equatorial Guinea characterised by HUMTH01, HUMVWA31A, HUMCSF1PO, HUMTPOX, D3S1358, D8S1179, D18S51 and D19S253 STR polymorphisms.

Allele frequencies for eight STR loci (HUMTH01, HUMVWA31A, HUMCSF1PO, HUMTPOX, D3S1358, D8S1179, D18S51, D19S253) have been analysed in the Bubi population of Bioko Island, Equatorial Guinea. For all loci, no deviation from Hardy-Weinberg equilibrium was found. Data obtained were compared with that of Caucasian and African populations. Significant differences were found for all systems between all the black populations compared and the Caucasoid population. Similarities were observed between the Bubi and Zimbabweans, and also with African American populations. Also, more affinities were observed between Zimbabweans and Ugandans and Ovambos than between these groups and the Bubi population. From these comparisons it is suggested that in Africa, as in other continents, there is a certain genetic heterogeneity.

Black People↗
PubMed2001

Accumulation of metals in autopsy tissues of subjects living in Tarragona County, Spain.

The concentrations of arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), lead (Pb), manganese (Mn), mercury (Hg), nickel (Ni), tin (Sn), vanadium (V) and zinc (Zn) were determined in autopsy tissues collected from subjects who at the time of death had lived in Tarragona (Catalonia, Spain) over a period of, at least, the previous 10 years. Samples of liver, lung, kidney, brain and bone were obtained from a total of 78 non-occupationally exposed subjects, autopsied between 1997 and 1999. Arsenic, Cd, Co, Cr, Cu, Pb, Mn, Hg, Ni, Sn, V and Zn were determined by inductively coupled plasma spectrometry (ICP/MS). The results were analyzed with respect to age, sex, smoking and drinking habits, and the subject's place of residence. Most tissue concentrations of As, Co, Cr, Hg and V were near to the analytical detection limit or, in some cases, even below it. However, the levels of Cu were slightly higher than the average concentrations found in other studies. Also, tissue concentrations of Mn, Sn and Zn were similar to those found in previous surveys, while those of Ni were lower than previously reported. Although the current levels of tissue Cd and Pb were comparatively lower than in studies in other areas, the distribution of both metals was similar to previously-reported trends. From the tissue metal concentrations observed in the present study, it would appear that neither environmental exposure nor a dietary excess of these elements could be considered a health hazard to people living in the study area.

Age Factors↗
PubMed2001

Effects of oral aluminum on essential trace elements metabolism during pregnancy.

The present study was conducted to assess in rats the effects of oral aluminum (Al) exposure on calcium (Ca), magnesium (Mg), manganese (Mn), copper (Cu), zinc (Zn), and iron (Fe) accumulation and urinary excretion. Three groups of plug-positive Sprague-Dawley (SD) rats were given by gavage 0, 200, and 400 mg/kg/d of Al(OH)3 on gestational days 1-20. Three groups of nonpregnant female SD rats of the same age received Al(OH)3 by gavage at the same doses for 20 consecutive days. At the end of the treatment period, 24-h urine samples were collected for analysis of Al and essential elements. Subsequently, all animals were sacrificed and samples of liver, bone, spleen, kidneys, and brain were removed for metal analyses. With some exceptions, the urinary amounts of Al, Mn, and Cu excreted by pregnant animals as well as the urinary levels of Al excreted by nonpregnant rats were higher in the Al-treated groups than in the respective control groups. Although higher Al levels were found in the liver of pregnant rats, the concentrations of Al in the brain of these animals were lower than those found in the same tissues of nonpregnant rats. With regard to the essential elements, tissue accumulation was most affected in pregnant than in nonpregnant animals. In pregnant rats, the hepatic and renal concentrations of Ca, Mg, Mn, Cu, Zn, and Fe, as well as the levels of Ca in bone, and the concentrations of Cu in brain were significantly higher in the Al-exposed groups than in the control group. According to the current results, oral Al exposure during pregnancy can produce significant changes in the tissue distribution of a number of essential elements.

Aluminum↗
PubMed2000

Pharmacokinetics and pharmacodynamics of mycophenolic acid in stable renal transplant recipients treated with low doses of mycophenolate mofetil.

Suboptimal doses of mycophenolate mofetil (MMF) are frequently employed in renal transplant (Tx) patients, with drug-related side effects or low weight. The aim of this study was to compare the mycophenolic acid (MPA) pharmacokinetic profile and its pharmacodynamic effect on patients receiving either standard (2 g) or low (1.5 g or 1 g) MMF doses, in order to evaluate the therapeutic efficacy of such low doses in inhibiting IMPDH activity. Twenty-seven stable renal Tx recipients aged 18-65 years, with a post-Tx follow-up of 38.5 +/- 44.8 months (6-166 months), receiving 1 g (n = 10), 0.75 g (n = 7) and 0.5 g (n = 10) MMF twice a day in association with cyclosporine and prednisone, were included. The control group was made up of untreated healthy volunteers (n = 5). Plasma concentrations of MPA were analyzed by reverse-phase HPLC. IMPDH activity was determined in lymphocytes by the measurement of 3H release from [2,8-(3)H] hypoxantine. The mean value of areas under the concentration-time curves (AUC(0-12)) of MPA throughout the 12-h dosing interval in patients treated with 2 g was higher than the corresponding data in patients receiving 1.5 g or 1 g bid, but no statistical differences were observed between the three groups. There was no correlation between MPA-AUC(0-12) values and MMF dose (expressed in g/day or g/kg per day). Predose MPA concentrations correlated only weakly with the respective MPA-AUC(0-12) values (r2 from 0.385 to 0.655), whereas an acceptable correlation was observed between MPA Cmax and MPA-AUC(0-12) (r2 from 0.626 to 0.759) in 2 g, 1.5 g, and 1 g MMF groups. An inverse relationship between MPA concentrations and IMPDH activity was observed. In general, the maximum MPA concentration was achieved from 1 h to 2 h after dosing, and the maximum inhibition of IMPDH was also from 1 h to 2 h after dosing. The evaluation of IMPDH activity demonstrated that there was a significant statistical difference between samples from 0 to 1 h (P = 0.008) and 0 to 2 h (P = 0.04). In conclusion, concentration-time profiles of renal transplant recipients administered 0.75 g and 0.5 g twice a day are slightly lower than those from the 2 g group, but nor significantly. On the other hand, inhibition of IMPDH activity was comparable in the three groups, indicating considerable interindividual pharmacodynamic variability. Pharmacodynamic monitoring of the degree of immunosuppression and its correlation with MPA plasma concentrations will be assessed further in future studies.

Adolescent↗
PubMed2000

Population study of Aymara Amerindians for the PCR-DNA polymorphisms HUMTH01, HUMVWA31A, D3S1358, D8S1179, D18S51, D19S253, YNZ22 and HLA-DQalpha.

Allele and genotype frequencies for eight DNA polymorphisms (HUMTH01, HUMVWA31A, D3S1358, D8S1179, D18S51, D19S253, YNZ22 and HLA-DQalpha) were determined in a population sample of Aymara Indians from Bolivia using PCR. No deviations of the observed allelic frequencies from Hardy-Weinberg equilibrium were found for all the systems studied. Significant differences in the allele frequencies were found between the Aymara and Quechua populations only for HUMVWA31A, which suggests a certain degree of genetic differentiation between the two populations.

Alleles↗
PubMed2000

Optimized procedure for lamotrigine analysis in serum by high-performance liquid chromatography without interferences from other frequently coadministered anticonvulsants.

The authors have developed a simple isocratic high-pressure liquid chromatographic (HPLC) assay for the simultaneous determination of lamotrigine and other frequently coadministered antiepileptic drugs in serum samples. Lamotrigine extraction was performed on a reversed-phase Oasis HBL preparation column. The eluates containing butalbital as internal standard were separated with a 7-microm Chromsystems C18 250 x 4.0 mm I.D. reversed-phase column at a temperature of 40 degrees C using a mobile phase consisting of pH 3.8 phosphate-acetonitrile buffer (55:45, v/v), at a flow rate of 0.8 mL/min. Ultraviolet detection was carried out at 210 nm. Measurement of the peak:height ratio allowed quantitative determination of the samples. The method was linear over a concentration range of 0.2 to 20 microg/mL for lamotrigine. Recovery was >90%. Within-day and between-day coefficients of variation ranged from 1.8% to 6.7%. The mean lamotrigine concentration was 8.01 +/- 5.63 microg/mL. After studying sera from 130 patients treated with lamotrigine the authors confirmed that associated antiepileptic therapy affected the serum lamotrigine levels, which were significantly higher in patients under valproic acid treatment.

Adolescent↗
PubMed2000

Excretion of hexachlorobenzene and metabolites in feces in a highly exposed human population.

A set of 53 individuals from a population highly exposed to airborne hexachlorobenzene (HCB) were selected to study the elimination kinetics of this chemical in humans. The volunteers provided blood, 24-hr urine, and feces samples for analysis of HCB and metabolites. The serum HCB concentrations ranged from 2.4 to 1,485 ng/mL (mean +/- SD, 124 +/- 278), confirming that this human population has the highest HCB blood levels ever reported. All analyzed feces samples contained unchanged HCB (range, 11-3,025 ng/g dry weight; mean +/- SD, 395 +/- 629). The HCB concentration in feces strongly correlated with HCB in serum (r = 0.85; p < 0.001), suggesting an equilibrium in feces/serum that is compatible with a main pulmonary entrance of the chemical and low intestinal excretion of nonabsorbed foodborne HCB. The equilibrium is also compatible with a nonbiliary passive transfer of the chemical to the intestinal lumen. Two HCB main metabolites, pentachlorophenol (PCP) and pentachlorobenzenethiol (PCBT), were detected in 51% and 54% of feces samples, respectively. All urine samples contained PCP and PCBT, confirming the conclusions of a previous study [Environ Health Perspect 105:78-83 (1997)]. The comparison between feces and urine showed that whereas daily urinary elimination of metabolites may account for 3% of total HCB in blood, intestinal excretion of unchanged HCB may account for about 6%, thus showing the importance of metabolism in the overall elimination of HCB. The elimination of HCB and metabolites by both routes, however, appears to be very small (< 0.05%/day) as compared to the estimated HCB adipose depots. Features of HCB kinetics that we present in this study, i.e., nonsaturated intestinal elimination of HCB and excretion in feces and urine of inert glutathione derivatives, may explain, in part, the absence of porphyria cutanea in this human population heavily exposed to HCB.

Adolescent↗
PubMed1999

Effect of age on vanadium nephrotoxicity in rats.

The present study was designed to assess potential age dependent differences of vanadium nephrotoxicity in the rat following parenteral administration of vanadate. Young (22 days) and adult (62 days) male Sprague-Dawley rats received i.p. injections of sodium orthovanadate at 10 mg/kg/day for 8 consecutive days. Two additional groups of control rats received i.p. injections of 0.9% saline during the same period. Significant age-differences were found in most of the parameters used as indicators of nephrotoxicity in young and adult rats, with adverse renal effects being more severe with age. Vanadium-induced morphologic changes in the kidney were also more pronounced with age. These findings agree with a higher renal concentration of vanadium in the group of adult rats treated with vanadate than in the vanadate-untreated group. The current results can be of concern if in the future, vanadium compounds can be administered in the treatment of diabetic patients.

Aging↗
PubMed1999

Blood chromium determination in assessing reference values in an unexposed Mediterranean population.

Plasma chromium levels were determined in 243 healthy subjects. The study group consisted of 134 men and 109 women, ages 19-71 yr, all residing in Barcelona in northeastern Spain. The study was designed to assess the reference levels for plasma chromium and to investigate its relationships to age and sex. The assays were performed by means of a graphite-furnace atomic absorption spectrometer. The mean plasma chromium concentration was 3.01 +/- 1.45 nmol/L, ranging from 0.6 to 6 nmol/L. The upper reference values in the 0.95 percentile for this population was 5 nmol/L. No significant differences were observed with respect to the subjects' sex.

Adult↗