Search PubMed⌕ Search

Biomedical subjects

J Corbella

Publications and source records attributed to J Corbella.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1999

Prevention by sodium 4,5-dihydroxybenzene-1,3-disulfonate (Tiron) of vanadium-induced behavioral toxicity in rats.

Recent studies have shown that oral vanadate (V5+) administration results in behavioral toxicity in rats. The chelating agent Tiron (sodium 4,5-dihydroxybenzene-1,3-disulfonate) is an effective antidote in the removal of vanadium from vanadium-loaded rats. In this study, the protective activity of Tiron on vanadate-induced behavioral toxicity was evaluated in adult rats. Intraperitoneal treatment with Tiron at 235 or 470 mg/kg was initiated after 6 wk of oral sodium metavanadate administration (16 mg/kg/d) and continued for 2 wk. Although vanadate exposure did not result in a significant reduction in the general activity of the animals in an open field, a lower active avoidance acquisition could be observed. However, the vanadate-induced behavioral deficit was reverted by Tiron administration at 470 mg/kg. The present results suggest that Tiron may protect, at least in part, against metavanadate-induced behavioral toxicity.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed1999

Biotransformation and clearance of 3-(phenylamino)propane-1,2-diol, a compound present in samples related to toxic oil syndrome, in C57BL/6 and A/J mice.

In May 1981, a massive food-borne intoxication occurred in Spain. The so-called toxic oil syndrome (TOS) was associated with the consumption of aniline-denatured and refined rapeseed oil that was illegally sold as edible olive oil. Fatty acid anilides and fatty acid derivatives of 3-(phenylamino)propane-1,2-diol were detected in oils and implicated as potential toxic agents and markers of toxic oil batches. Epidemiological evidence points to 3-(phenylamino)propane-1,2-diol derivatives as the putative toxic agents, which were generated during the refining process at the ITH refinery. Here we present the biotransformation and clearance of 3-(phenylamino)propane-1,2-diol (PAP) administered intraperitoneally to A/J and C57BL/6 mice that have been proposed as a murine model for the immunological features of TOS. Mice eliminated 6 microCi of [U-(14)C]PAP during a 24 h period, mostly in urine. Animals exhibited urine elimination rates of 70 and 36% in A/J and C57BL/6 strains, respectively. A/J mice exhibited no increase in the elimination rate when induced with beta-naphthoflavone, whereas C57BL/6 did increase the rate of elimination to 57%. Feces contributed to a lesser extent to the elimination rate (0.6 and 3.3% in A/J and C57BL/6 mice, respectively). Radioactivity remaining in organ tissues was lower than 1% (liver, lung, kidney, spleen, heart, and muscle). Metabolic species in urine were identified by HPLC coupled to UV and radioisotope detectors and further GC/MS analyses. 2-Hydroxy-3-(phenylamino)propanoic acid metabolite was the major chemical species excreted in urine in both strains, in both control and induced animal groups. This compound was the main urinary metabolite of PAP, and unmetabolized PAP excreted in urine constituted less than 1% of the total administered dose. Two additional highly polar metabolites also detected in urine were identified as 3-[(4'-hydroxyphenyl)amino]propane-1,2-diol and 2-hydroxy-3-[(4'-hydroxyphenyl)amino]propanoic acid. These findings are the first reported on PAP metabolism and clearance in mice strains and suggest that PAP can be extensively metabolized in vivo and potential reactive species can be generated.

Animals↗
PubMed1999

Genetic polymorphism of glutathione S-transferase P1 gene and lung cancer risk.

OBJECTIVES: The human GSTTP1 gene is polymorphic with an A-->G transition in exon 5 causing a replacement 105 Ile-->Val in the GSTP1 protein. The two isoforms, encoded by the alleles GSTP1*A and GSTP1*B, respectively, show different catalytic efficiencies towards some carcinogenic epoxides. In this study we have addressed the possible role of the Ile105Val GSTP1 polymorphism in lung cancer susceptibility. METHODS: The polymorphic site was genotyped by RFLP in a group of lung cancer patients (n = 164) and in two control groups (healthy smokers, n = 132; general population, n = 200). All patients and controls were Northwestern Mediterranean Caucasians of the same ethnic origin. RESULTS AND CONCLUSIONS: The cancer patients showed frequencies of GSTP1*A/A; GSTP1*A/B and GSTP1*B/B (50%, 38%, 11%, respectively) very similar to those of both control groups (healthy smokers: 48%, 41%, 11%). After adjusting for age, sex and smoking status, no association was found between the GSTP1*B allele and lung cancer risk (OR: 1.18; 95% CI: 0.67-2.07). The Ile105val GSTP1 polymorphism was also analysed in combination with the GSTM1 and GSTT1 genes. The results showed that allelism at GSTP1 did not increase the risk associated with the GSTM1 or GSTT1 deletions.

Adult↗
PubMed1998

Serum and urine fluoride concentration: relationships to age, sex and renal function in a non-fluoridated population.

Serum and urine fluoride levels were determined in 250 healthy subjects (15-90 years, 122 men and 128 women) residing in Catalonia, Spain, and in 150 patients (20-81 years, 84 men and 66 women) with chronic renal failure undergoing regular dialysis treatment, living in the same geographical area, to determine normal range and to investigate its relationships to age, sex and renal function. Serum and urine fluoride were determined by a fluoride ion specific electrode system. Mean (+/- S.D.) serum fluoride concentration was 17.5 +/- 9.5 micrograms/l, ranging from 1 to 47 micrograms/l, in the control group and 58 +/- 31 micrograms/l, ranging from 28 to 185 micrograms/l, in renal patients. Urine fluoride concentration in the healthy group was 671 +/- 373 micrograms/24 h, ranging from 156 to 1900 micrograms/24 h. Fluoride status in the patient group was significantly greater than the control group. There was significant correlation between serum fluoride and age. No sex related difference was found.

Adolescent↗
PubMed1998

Serum and urine ionic fluoride: normal range in a nonexposed population.

The present study was undertaken to evaluate the fluoride status in the general healthy population of Barcelona. Serum and urine fluoride ionic concentration was determined in a random sample of 250 subjects (age range 15-90 yr) by the Orion fluoride electrode system to determine the normal range of fluoride in this population. The results obtained show that in the general population of Barcelona, fluoride ionic serum concentration ranges between 1 and 47 microg/L (x = 17.5 +/- 9.7 microg/L) and fluoride ionic urine concentration ranges between 156 and 1990 microg/24 h (x = 671 +/- 373 microg/24 h). The mean serum fluoride concentration of the younger population was shown to be significantly greater (p < 0.05) than that of the older group. No sex-related difference was found.

Adolescent↗
PubMed1998

Influence of posttransplant time on dose and concentration of tacrolimus in liver transplant patients.

The dosage of tacrolimus (D), the trough blood concentrations (C) and the evolution of the D/C ratio were followed for 1 year after transplantation in so adult patients (38 males and 12 females) undergoing liver allograft. A total of 1489 samples were analysed by the IMx tacrolimus method. The overall median concentration was 11.27 ng/ml. During the 1st month the median of the tacrolimus levels was 8.4 ng/ml, and 73.1% of the analysed samples were within the established therapeutic range. The median oral tacrolimus dose was progressively reduced from 0.12 mg/kg per day during the 1st month to 0.06 mg/kg per day at the end of studied period. A significant negative association was observed between the D/C ratio and the post-transplantation period (r = -0.3892; P < 0.0001). The median D/C ratio ranged from 0.0144 at 1st month to 0.0053 at 1 year. Significant D/C declines were observed after the 1st and 3rd months posttransplant. The decrease in corticosteroid doses and the increase in serum albumin may explain the reduction in clearance with time.

Adult↗
PubMed1998

Silicon reduces aluminum accumulation in rats: relevance to the aluminum hypothesis of Alzheimer disease.

In recent years, a possible relation between the aluminum and silicon levels in drinking water and the risk of Alzheimer disease (AD) has been established. It has been suggested that silicon may have a protective effect in limiting oral aluminum absorption. The present study was undertaken to examine the influence of supplementing silicon in the diet to prevent tissue aluminum retention in rats exposed to oral aluminum. Three groups of adult male rats were given by gavage 450 mg/kg/day of aluminum nitrate nonahydrate 5 days a week for 5 weeks. Concurrently, animals received silicon in the drinking water at 0 (positive control), 59, and 118 mg Si/L. A fourth group (-Al, - Si) was designated as a negative control group. At the end of the period of aluminum and silicon administration, urines were collected for 4 consecutive days, and the urinary aluminum levels were determined. The aluminum concentrations in the brain (various regions), liver, bone, spleen, and kidney were also measured. For all tissues, aluminum levels were significantly lower in the groups exposed to 59 and 118 mg Si/L than in the positive control group; significant reductions in the urinary aluminum levels of the same groups were also found. The current results corroborate that silicon effectively prevents gastrointestinal aluminum absorption, which may be of concern in protecting against the neurotoxic effects of aluminum.

Administration, Oral↗
PubMed1998

Therapeutic drug monitoring of tacrolimus in liver transplantation, phase III FK506 multicenter Spanish Study Group: a two-year follow-up.

The aim of the Multicentric Liver Transplant Spanish Study was to evaluate tacrolimus therapy at the reduced, initial oral dose of 0.1 mg/kg per day to maintain the immunosuppressive potency of the drug and to avoid toxicity. The dosage of tacrolimus (D), the trough blood concentrations (C), and the evolution of the ratio (D/C) were followed up for 2 years after transplantation in 50 adult patients (38 men, 12 women) undergoing liver allograft transplantation. A total of 1732 samples were analyzed using the IMx tacrolimus method. The overall mean+/-SD concentrations were 10.84 ng/ml+/-5.32 ng/ml. During the first month, the median of the tacrolimus levels was 8.40 ng/ml, and 73.1% of the analyzed samples were within the established therapeutic range. The median oral tacrolimus dose was progressively reduced from 0.12 mg/kg per day during the first month to 0.058 mg/kg per day at the end of study period. A significant negative association was observed between the ratio of D/C and the post-transplantation period (r=-0.3624; p < 0.001). The median D/C ratio ranged from 0.0144 at the end of the first month to 0.0053 at 1 year. Significant declines in D/C were observed after the first and the third months after transplantation. The decrease in corticosteroid doses and the increase in serum albumin may explain the reduction in clearance with time.

Adult↗
PubMed1998

Multicenter comparison of first- and second-generation IMx tacrolimus microparticle enzyme immunoassays in liver and kidney transplantation.

Tacrolimus is a potent immunosuppressive drug successfully used for baseline and rescue immunosuppression in patients after liver and kidney transplantation. Data from several clinical trials have demonstrated the efficacy of tacrolimus in the prevention of allograft rejection, even at lower concentrations in the therapeutic range (5-15 microg/L). In fact, some patients with tacrolimus levels at less than 5 microg/L have excellent hepatic or kidney function. The limit of detection of the IMx Tacrolimus I assay (TAC I; Abbott Laboratories, IL) is only 5 microg/L and that of the lower tacrolimus calibrator is 10 microg/L. The second-generation assay uses the same monoclonal antibody and the same IMx technology but offers improved sensitivity, with a dynamic range from 0 microg/L to 30 microg/L (lower calibrator, 3 microg/L). The aim of this multicenter study was to evaluate the new IMx Tacrolimus II assay (TAC II) by assessing its precision, sensitivity, performance, and correlation degree relative to the IMx TAC I assay. The study was performed at three centers in Spain. The within-run coefficients of variation (CVs) obtained for the new assay, using each of the trilevel controls in replicates of 20 during 3 consecutive days, were 8.06%, 4.38% and 5.09% at 5 microg/L, 11 microg/L, and 22 microg/L, respectively. The corresponding between-run CVs obtained measuring each of the three controls in duplicate on 10 consecutive days were 9.54%, 6.38% and 5.75%. The limit of detection, with 97.5% confidence, was 1.22 microg/L. TAC II results (Y) were compared with those from the original TAC I assay (X) analyzing 293 whole blood samples from liver (n=145) and kidney (n=148) transplant recipients. The correlation study with patient samples (using the Passing-Bablock method) was y=1.056, x + 0.017, r=0.927. No statistically significant differences were observed between assays (TAC I versus TAC II) in the mean values obtained for total patients (9.89+/-5.42 microg/L versus 10.49+/-5.63 microg/L), liver patients (9.16+/-4.79 microg/L versus 10.00+/-5.20 microg/L), and kidney patients (10.62+/-5.87 micro g/L versus 10.98+/-5.99 microg/L). The new IMx TAC II assay demonstrated the same precision and accuracy that characterized the original assay but showed improved sensitivity to the demands of tacrolimus monitoring in the lower therapeutic range of drug concentrations.

Antibodies, Monoclonal↗
PubMed1998

Aluminium distribution and excretion: a comparative study of a number of chelating agents in rats.

The present study was conducted to assess in rats the comparative effects of a number of chelating agents on the urinary excretion and tissue distribution of A1. Adult male Sprague-Dawley rats received a single intraperitoneal dose of aluminium (A1) nitrate nonahydrate (0.24 mmol/kg). Ten min. after A1 injection 1,2-dimethyl-3-hydroxypyrid-4-one, 2,3-dihydroxybenzoic acid, picolinic acid, methylmalonic acid, ethylenediamine-di(o-hydroxyphenylacetic) acid, 1-benzyl-2-methyl-3-hydroxypyrid-4-one, 1-(p-methylbenzyl)-2-methyl-3-hydroxypyrid-4-one, 1-(p-methoxy-benzyl)-2-methyl-3-hydroxypyrid-4-one, 1-(p-chlorobenzyl)-2-methyl-3-hydroxypyrid-4-one, 1-benzyl-2-ethyl-3-hydroxypyrid-4-one, 1-(p-methyl-benzyl)-2-ethyl-3-hydroxypyrid-4-one, 1-[3-hydroxy-2-methyl-4-oxopyridyl]-2-ethanesulfonic acid and 1-benzyl-(4-carboxylic acid)-3-hydroxy-2-methyl-4-oxopyridine were given by gavage at 1.79 mmol/kg. A control group received similar volumes of distilled water. An additional group of rats received a subcutaneous injection of desferrioxamine at 1.79 mmol/ kg. Urine samples were collected daily for three consecutive days and the animals were killed after this period. Samples of brain, bone, liver, kidney and spleen were collected. Although desferrioxamine, 1,2-dimethyl-3-hydroxypirid-4-one, 1-(p-methylbenzyl)-2-methyl-3-hydroxypyrid-4-one, 1-(p-methoxybenzyl)-2-methyl-3- hydroxypyrid-4-one, 1-(p-methylbenzyl)-2-ethyl-3-hydroxypyrid-4-one, 1-[3-hydroxy-2-methyl-4-oxopyridyl]-2-ethanesulfonic acid and 1-benzyl-(4-carboxylic acid)-3-hydroxy-2-methyl-4-osopyridine significantly enhanced the total excretion of A1 into urine, only treatment with 1-(p-chlorobenzyl)-2-methyl-3-hydroxypyrid-4-one and 1-benzyl-2-ethyl-3-hydroxypyrid-4-one significantly reduced A1 concentrations in all analyzed tissues. No beneficial effects of the remaining chelators on Al mobilization were observed. Further studies on the effects of some 3-hydoxrypyrid-4-ones on A1 removal can be of interest for the treatment of A1 accumulation and toxicity.

Aluminum↗
PubMed1998

Quechua Amerindian population characterized by HLA-DQ alpha, YNZ22, 3'APO B, HUMTH01, and HUMVWA31A polymorphisms.

Allele and genotype frequencies of DNA polymorphisms were determined in a population sample of Quechua (n = 113) using the polymerase chain reaction (PCR). We report data on the frequencies of HLA-DQ alpha, YNZ22, 3'ApoB, HUMTH01 and HUMVWA31A alleles and the distribution of the different genotypes. No significant deviations between observed and expected numbers were found, thus assuming the Hardy-Weinberg equilibrium.

Bolivia↗
PubMed1998

Effects of simultaneous administration of desferrioxamine and tacrine in rats.

Tacrine (1,2,3,4-tetrahydro-9-aminoacridine), a reversible cholinesterase inhibitor, was effective in the treatment of Alzheimer's disease (AD). In turn, desferrioxamine (DFO), a chelating agent with ability to chelate iron and aluminum (Al), produced a 50% decrease in the rate of cognitive decline in patients with AD. Since combined therapy with tacrine and DFO might be more effective than individual administration of these drugs for the treatment of AD patients, this study evaluated the toxic effects of concomitant administration of tacrine and DFO to rats. Three groups of 8 rats each received the following treatments for 8 w: 80 mg DFO/kg/d i.m., 7.5 mg tacrine/kg/d po, or 80 mg DFO/kg/d i.m. +7.5 mg tacrine/kg/d po. A control group received distilled water by gavage daily and a 0.9% saline injection i.m. The administration of DFO + tacrine for 8 w did not increase most of the side effects caused by the individual DFO or tacrine administrations. These results open the possibility of considering the effectiveness of simultaneous administration of DFO and tacrine as a palliative treatment for AD patients.

Animals↗