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M Borràs

Publications and source records attributed to M Borràs.

16 recordsLinked to original sources
PubMed2004

Biomarkers of genotoxicity and other end-points in an integrated approach to environmental risk assessment.

Risk is defined as the probability of a given toxicological hazard resulting in actual biological harm. This involves some form of mathematical relationship between exposure and toxic effects. Simplified models based on laboratory testing in surrogate species neglect potentially important factors in real life situations. Our own approach to the study of atmospheric and edaphic pollution, focused on realism, includes the use of sentinel species (animals as prospectors and integrators of information, along both the spatial and the temporal axes) and selected biomarkers. We aim to: (i) consider pollution as a complex mixture; (ii) take into account homeostasis of the environment and of living organisms; (iii) be realistic (all data obtained in the field; calculations based on actual effects; exposure measured as internal dose). The proposed test battery divides toxicological information into four blocks: systemic effects (serum biochemistry and histopathology in wild wood mice), reproduction (epididymis cell count in mice, malformations in amphibian larvae), genotoxicity (Comet test in mice and earthworms) and population effects (abundance and diversity in arthropods). Each block is represented by the sum of the results of the tests performed within the block (presented as a severity score from 0 to 3). A final value is obtained to represent the integrated toxicological harm (ITH) occurring at a given location. To assess exposure, taking into account bioavailability, we propose (i) for soil contamination studies, measuring EROD activity in liver; (ii) for atmospheric pollution, the gaseous fraction is taken from immission gases analysis, while the solid fraction is assessed through levels of metals in sentinel organisms, the values of both fractions then being combined. Finally, a regression line is established for exposure versus ITH in four to five locations with decreasing exposure levels, ranging from the immediate neighbourhood of the pollution focus to controls, following the main dissemination line. In this model we may interpolate new exposure data to find the corresponding predicted ITH. Such a prediction may be directly interpreted as a form of risk assessment or, alternatively, these pairs (toxicological harm/exposure) could then be related to a conventional scale of ecotoxicological risk.

Biomarkers↗
PubMed1999

Vitamin D receptor genotype influences parathyroid hormone and calcitriol levels in predialysis patients.

BACKGROUND: BsmI vitamin D receptor (VDR) gene polymorphism has been associated with the severity of hyperparathyroidism in patients on hemodialysis. The aim of this study was to analyze the influence of this polymorphism on parathyroid function and serum calcitriol levels in patients with different degrees of chronic renal failure (CRF) before dialysis. METHODS: A total of 248 CRF patients, divided into three groups according to creatinine clearance (CCr; mild CRF group> 60 to </=85 ml/min, N = 54; moderate CRF group> 35 to </=60 ml/min, N = 113; severe CRF group> 10 to </=35 ml/min, N = 81), had their serum intact parathyroid hormone (iPTH) and calcitriol levels measured and BsmI genotype frequencies estimated by polymerase chain reaction (PCR) analysis. Diabetics, those on treatment with steroids, vitamin D or derivatives, and phosphorus binding agents were excluded. All those with serum calcium levels of <2.25 mmol/liter or> 2.5 mmol/liter and serum phosphorus levels of> 1.6 mmol/liter or who needed phosphorus binding agents were excluded. The statistical analysis was done with the general factorial analysis of variance entering first PTH and then calcitriol as the dependent variable; the genotype (BB, Bb and bb), sex and CCr group were defined as factors; and covariables included serum calcium, serum phosphorus, 1/creatinine versus time slope, PTH when calcitriol was the dependent variable, and calcitriol when PTH was the dependent variable. RESULTS: When serum PTH levels were entered as the dependent variable, serum calcium, CCr group, and the interaction of genotype with the CCr group were found to be significant factors (P = 0.025, P <0.001 and P = 0.039, respectively). When serum calcitriol levels were entered as the dependent variable, genotype, the interaction of genotype with CCr, the CCr group, and the 1/creatine versus time slope were found to be significant (P = 0.027, P = 0.028, P <0.001 and P = 0.044, respectively). The marginal means of PTH, adjusted with the general factorial analysis of variance across the three groups were: (a) mild CRF group, BB 5.3 pmol/liter (CI 0 to 13.8), Bb 5.5 pmol/liter (CI 2 to 9), bb 5.4 pmol/liter (CI 0.6 to 10.2); (b) moderate CRF group, BB 6.2 pmol/liter (CI 1.5 to 10.9), Bb 7.8 pmol/liter (CI 5.3 to 10.3), bb 7.5 pmol/liter (CI 4.8 to 10.1); (c) severe CRF group, BB 9.3 pmol/liter (CI 4.2 to 14.3), Bb 17.1 pmol/liter (CI 13.9 to 20.2), bb 21.9 pmol/liter (CI 18.7 to 25.2). The marginal means of calcitriol adjusted with the general factorial analysis of variance across the three groups were: (a) mild CRF group, BB 47 pg/ml (CI 37 to 57), Bb 40.9 pg/ml (CI 37 to 44.8), bb 32.6 pg/ml (CI 26.8 to 38. 4); (b) moderate CRF group, BB 24.1 pg/ml (CI 18.3 to 29.8), Bb 26.6 pg/ml (CI 23.5 to 29.7), bb 25.3 pg/ml (CI 22 to 28.6); (c) severe CRF group, BB 27.4 pg/ml (CI 21.3 to 33.5), Bb 19.4 pg/ml (CI 15.5 to 23.2), bb 20.4 pg/ml (CI 16.1 to 24.7). CONCLUSION: The progression of hyperparathyroidism is slower in predialysis patients with BB genotypes than in the other genotypes. Also, calcitriol levels are less reduced in the BB genotype, which may act to lessen the severity of secondary hyperparathyroidism.

Aged↗
PubMed1998

Hormone dependency of splenic iron stores in the rat: effect of oestrogens on the recuperation of reserves in ferrodeficient subjects.

Splenic iron stores are negligible in prepuberal rats, increasing quickly from the age of 2 months (at which moment sexual differences become apparent) and stabilizing around 3 months, when females show values approximately two-fold greater than males. Castration, adrenalectomy and hormone replacement studies show that the amount of iron stored depends directly on circulating oestrogens and is slightly but not significantly decreased, in our experimental conditions, by testosterone. The role of oestrogens is emphasized by the high correlation obtained, according to a hyperbolic regression model, between splenic iron values and doses of hormone administered to ovariectomized females. In ferrodeficient females (chronic phlebotomy), oestradiol had a positive effect on the replenishment of the stores, superior to that of iron dextran, and improved by combined treatment. However, iron levels found after a single dose were less than those found in nonphlebotomized animals.

Adrenalectomy↗
PubMed1997

Protein synthesis is not implicated in the ligand-dependent activation of the estrogen receptor in MCF-7 cells.

In MCF-7 cells, estrogen receptor (ER) elimination occurs rapidly under stimulation with estradiol (E2) at 1 nM ('ER processing'); cycloheximide (CHX) at 50 microM impedes this phenomenon. ER processing is also observed when E2 is removed after the first hour of incubation, indicating that the role of the hormone would be limited to the initiation of this process. When CHX is removed at the same time, receptor processing and, later, the induction of progesterone receptor (PgR) both proceed. The initial estrogenic signal which activates ER is therefore not influenced by CHX. In support of this conclusion, no effect of the drug on E2 binding affinity of residual ER was detected. A similar result was recorded for a series of estrogens and antiestrogens, indicating that CHX exerts no influence on the potential agonistic/antagonistic potency of any ligand. Size-exclusion chromatography (FPLC) revealed that [3H]E2-induced ER activation leads to the cleavage of the native receptor (67 kDa) into low molecular weight isoforms which subsequently become less detectable over time (proteolysis). In the presence of CHX, such ER isoforms persist, confirming the absence of interference of the drug with the activation step. When the cells were prelabelled with [3H]tamoxifen aziridine ([3H]TAZ) before their exposure to E2, ER cleavage could not be detected due to the lack of activation potency of the antiestrogenic ligand. However, the [3H]TAZ-ER complexes were subjected to E2-induced processing; CHX blocked this phenomenon, which is associated with the maintenance of ER synthesis and activation.

Binding, Competitive↗
PubMed1995

Low-calcium dialysate stimulates parathormone secretion and its long-term use worsens secondary hyperparathyroidism.

The long-term clinical effects of the use of a low calcium concentration in the dialysate are largely unknown. For this reason, the influence of low-calcium dialysate on parathyroid hormone (PTH) secretion in hemodialysis patients and its long-term effect on the severity of secondary hyperparathyroidism were studied. In 35 hemodialysis patients, the dialysate calcium concentration was lowered from 1.75 to 1.25 mmol/L. Twelve months later, serum iPTH levels increased significantly from 18.6 to 33.2 pmol/L and so did alkaline phosphatase levels, from 210 to 330 IU/L, without significant changes in serum calcium or phosphorus levels. Hemodialysis with low-calcium dialysate (1.25 mmol/L) induced a net calcium loss in 10 patients, without modifications in ionized serum calcium levels. In addition, mean serum iPTH increased 20% over baseline levels, reaching the maximal level at 30 min after the start of hemodialysis with low-calcium dialysate. In contrast, mean serum iPTH levels drop dramatically at 30 min of hemodialysis with high-calcium dialysate (1.75 mmol/L). It was concluded that low-calcium dialysate worsens secondary hyperparathyroidism in hemodialysis patients, probably by inducing a negative calcium balance and causing repetitive stimulation of PTH secretion in each dialysis. The maintenance of normal serum calcium levels could be due to PTH-induced calcium mobilization from bone.

Adolescent↗
PubMed1995

Peritoneal transport evaluation in peritonitis: comparison between methods.

Peritoneal dialysis patients may need solute permeability transport evaluation during acute peritonitis. The aim of this study was to assess if the simplified mass transfer coefficient (MTCS) or the peritoneal equilibration test (PET) was equivalent to the complex MTC (MTCX) in solute transport evaluation during acute peritonitis in continuous ambulatory peritoneal dialysis (CAPD) patients. We studied 15 episodes of peritonitis (PTIS). Results were compared to a baseline patient study (PRE) and a control study done 30 days after diagnosis of peritonitis (POST). All peritoneal evaluation methods showed a significant increase in solute transport during acute peritonitis compared to baseline and control studies. There was an acceptable correlation between MTCX and simplified methods including the PET in the baseline and control studies. However, correlation between MTCX and simplified methods decreased during acute peritonitis. Likewise, the PET showed a better correlation with MTCX than MTCS. We conclude that the PET has an acceptable agreement with MTCX even during acute peritonitis, so the PET can be a useful tool in evaluating peritonitis-induced peritoneal permeability changes.

Acute Disease↗
PubMed1988

Use of modified Fraser's stain in Promoting Activity Test (PAT).

The Promoting Activity Test (PAT) requires a staining procedure that allows rapid, accurate and reliable counting of mitotic figures. We propose use of Fraser's kernechtrot-crystal violet technique, but eliminating the picric-alcoholic differentiation to avoid fading. This modified protocol gives higher mitotic counts in adult mouse adrenal cortex than the hematoxylin-eosin originally used, especially with respect to less conspicuous prophases.

Adrenal Cortex↗