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Biomedical subjects

M Miranda

Publications and source records attributed to M Miranda.

At least 19 recordsLinked to original sources

Use of dogs as indicators of metal exposure in rural and urban habitats in NW Spain.

Many different species have been used in environmental biomonitoring studies in diverse habitats including forest, farmland, and urban and sub-urban areas. However, there is little information on domestic animals living in rural or urban habitats and exposed to the same pollutants as the human population. In this connection, pets could prove to be good indicators of human metal exposure since they closely share the same environment as their owners, and are therefore exposed, at least in part, to the same pollutants. The present study investigated toxic metal exposure in dogs in NW Spain and compared metal exposures between dogs from rural and urban habitats, considering the influence of diet, sex and age. Samples of liver and kidney from 57 male and female dogs, aged between 6 months and 18 years, were collected after euthanasia at veterinary clinics. Samples were acid-digested and metal concentrations determined by ICP-MS. Geometric mean concentrations of metals in the liver and kidney (microg/kg wet weight) were 12.6 and 15.9 for arsenic, 58.0 and 175 for cadmium, 32.7 and 53.4 for mercury, and 57.7 and 23.1 respectively. Hepatic lead concentrations were significantly higher (p<0.05) in dogs fed commercial diets than dogs fed home-made feed (32%) or a mixture of commercial and home-made feeds (95%). Mercury concentrations in the kidney were significantly higher (3-fold, p<0.05) in dogs from urban areas than in dogs from rural areas. Cadmium levels in kidney were significantly higher (p<0.05) in females (67%) and increased with age (p<0.001). Although no human samples were obtained in this study and no direct correlations between dogs and human metal exposure have been conducted, given our results pets could be suggested as surrogate indicators of human metal exposure.

Animal Nutritional Physiological Phenomena↗

Influence of copper status on the accumulation of toxic and essential metals in cattle.

The aim of the present study was to assess whether the use of pig slurry and associated copper accumulation in calves grazing pastures fertilized with pig slurry from the Deza region in NW Spain has a significant influence on toxic metal and essential metal levels, and to investigate whether copper accumulation is correlated with the levels of these other metals. Correlations between copper, toxic metals (cadmium, lead) and essential metals (molybdenum, iron, zinc, selenium, manganese and cobalt) concentrations were evaluated in liver and kidney of 195 calves from the region of Deza. Metal concentrations were determined by ICP-OES and correlations between pairs of elements by Pearson correlation analysis. There was a strongly significant positive association between copper and lead in the liver. Considering the trace metals, copper in the liver showed significant positive correlations with cobalt in both liver and kidney, and with molybdenum in the liver. In addition, significant correlations were observed between copper and most essential metals in kidney. These associations are similar to those found in different animal species experimentally dosed with copper and other metals, as well as in cattle exposed to normal copper concentrations.

Animals↗

Expression of TWEAK and its receptor Fn14 in human subcutaneous adipose tissue. Relationship with other inflammatory cytokines in obesity.

TWEAK, a cytokine of the TNF family, has been found to be expressed under different inflammatory conditions but no data is available concerning the expression of this cytokine and its receptor (Fn14) in human obesity. In the present work we have evaluated the expression of many pro-inflammatory TNF system cytokines (TNF-alpha, TWEAK and their respective receptors, TNFR1, TNFR2 and Fn14) in human adipose tissue of 84 subjects some with different degree of obesity and type 2 diabetes, and its relation with inflammation by also measuring the expression of macrophage marker CD68. We detected expression of TWEAK and Fn14 in isolated mature adipocytes and in the stromovascular fraction. Additionally, we found that LPS upregulates the expression of both genes on THP-1 human monocytic cell line. TWEAK was expressed in adipose tissue of all studied subjects with no differences between obesity group, and was associated with Fn14 expression in morbid obese, mainly in women with type 2 diabetes. The data obtained here also showed that TNF-alpha and TNFR2 mRNAs were significantly more expressed in subcutaneous adipose tissue of subjects with morbid obesity compared to obese and non-obese subjects. In contrast, TNFR1 gene expression was negatively associated with BMI. Our results suggest that the expression of TNF-derived pro-inflammatory cytokines are increased in severe obesity, where macrophage infiltrate could modulate the inflammatory environment through activation of its receptors.

Adipose Tissue↗

Available lysine content in human milk: stability during manipulation prior to ingestion.

UNLABELLED: Available lysine content is an indicator of protein quality and nutritional value of milk. Many studies have examined the effects of extraction, treatment and storage of human milk upon its components, though no references are found regarding the possible changes in milk quality as defined by its content in essential amino acids such as lysine. The present study investigates the available lysine content in human milk and the variations in lysine resulting from milk manipulation as follows: (a) Cold storage (refrigeration at 4 degrees C for 48 hours, and frozen for 15 days at -20 degrees C); (b) Thermal treatment under conditions of low (Holder)(63 degrees C/30 minutes) and high pasteurization (75 degrees C/15 seconds). The results obtained show a decrease in milk lysine concentration after storage in both refrigerated and frozen samples. Pasteurization causes a highly significant loss of available lysine. The lysine losses were greater on applying low pasteurization versus the more gentle conditions of high pasteurization. CONCLUSIONS: While manipulation through cold storage or thermal treatment does not affect the protein content of human milk, its protein quality is modified. When human milk must be subjected to hygienization, it is preferable to apply high temperature treatment (75 degrees C, 15 seconds) than habitual pasteurization (63 degrees C, 30 minutes).

Biological Availability↗

Atosiban vs ritodrine used prophylactically with cerclage in ICSI pregnancies to prevent pre-term birth in women identified as being at high risk on the basis of transvaginal ultrasound scan.

Our objective was to compare the effectiveness and safety of atosiban and ritodrine, in pregnancies obtained by intracytoplasmic sperm injection (ICSI) undergoing cervical cerclage. Data from a prospective study were compared with those from a retrospective study. Sixteen ICSI pregnant women, 20-24 weeks' gestation and maternal age >18 years, received atosiban (bolus dose 6.75 mg i.v., followed by 300 microg/min i.v. for 3 h and 100 microg/min i.v. for 45 h). Cervical cerclage was performed 3 h after starting atosiban. The control group (group B) of 16 ICSI pregnant women were matched and received ritodrine hydrochloride (100-350 microg/min) for 48 h. Cervical cerclage was performed after 24 h. Pre-term rupture of membranes occurred within 48 h of cervical cerclage in one woman receiving atosiban and in four women receiving ritodrine. There was no significant difference in terms of pregnancies not delivered at 48 h (short-term tocolysis) and at 7 days (long-term tocolysis). However, there was a significantly higher incidence of maternal tachycardia with ritodrine compared with atosiban (p < 0.001). The mean gestational age at delivery was significantly higher for atosiban compared with ritodrine (36 vs 33 weeks; p < 0.001). The neonatal outcome was poorer for ritodrine than atosiban, as there were very low birth weight infants (p = 0.008), resulting in lower Apgar scores (p = 0.005) and there were more neonates requiring a long stay in the neonatal intensive care unit (p = 0.005). We conclude that atosiban is associated with a significantly lower incidence of maternal tachycardia and improved neonatal outcome compared with ritodrine.

Adult↗

Long-term follow-up of blood lead levels and haematological and biochemical parameters in heifers that survived an accidental lead poisoning episode.

Four of 10 heifers that survived an episode of lead poisoning caused by an old broken battery in the pasture were periodically monitored from days 14 to 205 after the episode, with the aim of (i) determining the time-course of lead clearance from blood; and (ii) assessing whether the exposed cattle showed changes in haematological parameters or serum markers of hepatic and renal function (e.g. serum creatinine level) that might be useful as indicators of subclinical toxicity. On the first sampling day, lead levels in blood varied between 0.478 and 0.758 mg/l. The half-life of lead in blood was rather variable, ranging from 68 to 266 days. Despite the high blood lead levels, no significant changes were detected in haematological parameters or hepatic/renal markers, all of which remained within normal ranges. In conclusion, these cattle that survived an episode of lead poisoning may constitute a risk for human consumers, but do not appear to have suffered severe health consequences themselves.

Animals↗

[Oxidative stress in a model of experimental diabetic retinopathy: the utility of peroxinytrite scavengers].

PURPOSE: The retina is the neurosensorial tissue of the eye and is extremely rich in polyunsaturated lipid membranes. This feature makes it especially sensitive to oxygen and/or nitrogen activated species and lipid peroxidation. Several authors have postulated the importance of superoxide (O2-) and peroxynitrite production in the development of diabetic complications. In the present study, we have used two different antioxidants, ebselen and lutein, that present as a common feature their peroxynitrite scavenging capacity, to ameliorate the oxidative stress that exists in the retina in diabetic patients. METHODS: Hyperglycemia was accomplished by the intraperitoneal injection of Alloxan in a mouse model of diabetic retinopathy. Malondialdehyde (MDA) and glutathione (GSH) concentrations in eye homogenates (without the lens) were determined. We also recorded serial electroretinograms (ERG) and measured latency and implicit times. RESULTS: The MDA concentration increased and the GSH concentration decreased in the eyes of the diabetic animals. Treatment with ebselen and lutein restored the MDA and GSH concentrations to control values. Latency and implicit times were not affected by the diabetes. CONCLUSION: New studies are required to better understand the protective mechanism of ebselen and lutein in this model of experimental diabetic retinopathy.

Animals↗

The role of metallothionein and zinc in hepatic copper accumulation in cattle.

The role of metallothionein (MT) and zinc (Zn) in hepatic copper (Cu) accumulation in calves from a region in North-West Spain has been investigated. In this region there is intensive pig farming, and animals with liver Cu concentrations above normal are not uncommon. Concentrations of hepatic MT were not related to Cu accumulation but were strongly dependent on the Zn status of the animal. When analysing the metal content bound to MT it was observed that Cu-MT values, in the same way as Zn-MT, were directly correlated with MT concentrations in the liver, indicating that although Cu is a poor inducer of MT synthesis, it can compete with Zn for MT binding sites. The ability of Cu to displace Zn from MT is highly dependent on the Cu:Zn ratio in the cell, Cu being the main metal in MT at the higher levels of Cu exposure in Galician cattle. In spite of this, the percentage of the total hepatic Cu bound to MT is very low in these animals, indicating that cattle have a very limited capacity to accumulate Cu-MT in the liver, and may therefore have a greater susceptibility to Cu toxicosis.

Animals↗

Changes in the survival of patients with systemic lupus erythematosus in childhood: 30 years experience in Chile.

The objective of this study was to analyse the survival rate and cause of death in children with systemic lupus erythematosus (SLE) during the past 30 years in Chile. A retrospective analysis was performed between 1969 and 2000 on patients attending pediatric rheumatology centres in Santiago, Chile. Survival and causes of death in 31 children followed from 1969 to 1980 fulfilling the 1982 American College of Rheumatology criteria for SLE and treated with oral steroids were compared with 50 other patients who were treated with oral steroids and an aggressive treatment of IV bolus of cyclophosphamide (38 patients) and azathioprine (12 patients). Global survival at five and 10 years follow-up for the patients studied from 1969 to 1980 was 68 and 40%, respectively. During the second study period these values were significantly improved and global survival reached 95% at five years and 90% at 10 years follow-up (P < 0.05). Survival at 10 years follow-up for patients with lupus nephropathy increased from 28% (study period 1964-1980) to 86% (study period 1984-2000). Twelve children died (38%) during the 1964-1980 study period. The causes of death were six due to kidney failure, three due to infectious conditions and another three of unknown causes. During the 1980-2000 study period mortality reached 6% (three cases), two cases died of a lupus flare-up and one case due to infection. In the last three decades, we have seen an important increase in the survival of children with SLE, especially in those patients with renal involvement. Management with immunosuppressive drugs, such as IV cyclophosphamide or azathioprine has changed the prognosis in these children. These results demonstrate that our children with SLE increased their life expectancy but are now faced with new types of morbidity because of the sequelae related to the disease itself.

Adolescent↗

Effects of moderate pollution on toxic and trace metal levels in calves from a polluted area of northern Spain.

This study evaluated the contribution of anthropogenic pollution to toxic metal residues (Cd, Pb and As) in cattle in an industrialized area of Asturias (northern Spain), and investigated possible implications of toxic metal exposure for metabolism of essential metal elements (Cu, Zn, Fe, Mn). Samples of liver, kidney, muscle and blood from animals aged 9-12 months were obtained from an industrialized area (78 calves) and from a rural area (92 calves). Samples were acid-digested, and levels of metals determined by atomic absorption spectrophotometry. Cadmium and lead contents in the liver and kidney were moderately and significantly higher in calves from the industrialized area (Cd: liver 29.6, kidney 161; Pb: liver 38.1, kidney 38.3 microg/kg wet weight) than in calves from the rural area (Cd: liver 22.9, kidney 96.4; Pb: liver 20.7, kidney 15.9 microg/kg kg wet weight). Although these toxic metals were only moderately raised, our results suggest that they may nevertheless have interfered with trace element metabolism, as reported previously for severely polluted regions. Notably, copper levels in calves from the industrialized area were generally low, and nearly half of these animals showed tissue copper levels indicating risk of copper deficiency.

Animals↗

[Oxidative stress in a model for experimental diabetic retinopathy: treatment with antioxidants].

PURPOSE: Diabetic retinopathy is the primary cause of blindness in developed countries, and though strict glycemic control is desirable to prevent complications, this is not always achievable. Thus, adjunctive therapies are needed to help in preventing or delaying the onset of diabetic complications. We have studied the biochemical and functional changes in the retina of diabetic mice, and the ability of ebselen and lutein, two antioxidants, to reverse these effects, using as a comparison the effect of insulin therapy. METHODS: Alloxan injection was used to achieve hyperglycemia. Malondialdehyde (MDA) concentration in blood and glutathione peroxidase (GPx) activity in eye homogenate were measured. Serial electroretinograms (ERG) were recorded. RESULTS: MDA concentration in the blood was high in diabetic animals. GPx activity in eye homogenate decreased in the diabetic conditions. Maximal electroretinogram amplitude decreased in diabetic animals with respect to controls. Ebselen and lutein restored MDA levels, GPx activity and ERG amplitude, and had no effect on glycemia. CONCLUSION: These results call for further studies on ebselen or lutein as adequate adjunctive therapies for diabetes.

Animals↗

Oral contraceptive induced chorea: another condition associated with anti-basal ganglia antibodies.

Use of oral contraceptives is a recognised but infrequent cause of chorea. This type of chorea has usually been considered a reactivation of Sydenham's chorea by an unknown mechanism. A patient developed a chorea triggered by the use of oral contraceptives with no definite evidence of previous Sydenham's chorea or recent streptoccocal infections. However, the patient had positive anti-basal ganglia antibodies, which supports an immunological basis for the pathophysiology of this chorea.

Adult↗

Mercury concentrations in cattle from NW Spain.

Mercury is a toxic metal that is released into the environment as a result of various industrial and agricultural processes. It can be accumulated by domestic animals and so contaminate human foodstuffs. To date, there is no information on mercury residues in livestock in Spain and the aim of the present study was to quantify the concentrations of mercury in cattle in two of the major regions in north-west Spain, Galicia (a largely rural region) and Asturias, which is characterised by heavy industry and mining. Total mercury concentrations were determined in tissue (liver, kidney and muscle) and blood from 284 calves (6-10 months old) and 56 cows (2-16 years old) from across the whole of the two regions. Mercury was usually detected in the kidney (62.4-87.5% of samples) but most (79.5-96%) liver, muscle and blood samples did not contain detectable residues. Renal mercury concentrations did not differ between male and female calves but were significantly greater in female calves than in cows. Unexpectedly, kidney mercury concentrations were significantly higher in calves from the predominantly rural region of Galicia (geometric mean: 12.2 microg/kg w.wt.) than in animals from the industrialised-mining region of Asturias (3.40 microg/kg w.wt.). Overall, mercury residues in cattle from NW Spain were similar to those reported in cattle from non-polluted areas in other countries and do not constitute a risk to animal or human health.

Age Factors↗

Large-scale spatial variation in mercury concentrations in cattle in NW Spain.

Mercury (Hg) is a highly toxic environmental contaminant and man-made emissions account for between a quarter and a third of total atmospheric levels. Point discharges, particularly coal-burning power stations, are major sources of atmospheric Hg and can result in marked spatial variation in mercury deposition and subsequent uptake by biota. The aims of this study were to quantify the extent to which major point and diffuse sources of atmospheric Hg emissions affected accumulation of Hg by biota throughout Galicia and Asturias, two of the major regions in northwest Spain. We did this by relating renal Hg concentrations in locally reared cattle (n=284) to the proximity of animals to point and diffuse sources of Hg emissions. Mercury residues in calf kidneys ranged between non-detected and 89.4 g/kg wet weight. Point discharges from coal-fired power plants in Galicia had the most dominant impact on Hg accumulation by calves in Galicia, affecting animals throughout the region and explaining some two-thirds of the variation in renal residues between animals located directly downwind from the plants. The effects of more diffuse emission sources on Hg accumulation in calves were not distinguishable in Galicia but were detected in cattle from neighbouring Asturias. The impact of both point and diffuse sources in elevating environmental levels of bioavailable Hg and subsequent accumulation by cattle extended to approximately 140-200 km downwind from source.

Air Pollutants↗

Cadmium and lead accumulation in cattle in NW Spain.

This study investigated if differences in nutritional management (linked to feed composition and feed intake) could determine differences in the toxic metal accumulations in beef and dairy cattle in NW Spain. Cadmium and lead concentrations were determined in the liver, kidney and muscle of 57 cows (3-16 y-o) by inductively coupled plasma optical emission spectroscopy. Dairy cattle accumulated significantly higher cadmium and lead residues in liver (51.6 and 43.7 microg/kg fresh weight) than did beef cattle (35.7 and 14.7 microg/kg). In the kidney and muscle, cadmium and lead residues were similar in both dairy and beef cattle. The higher metal accumulations in the liver of dairy cattle could be related not only to higher dietary intake, but also to the higher hepatic metabolism associated with milk production.

Animal Feed↗

Interactions between toxic and essential trace metals in cattle from a region with low levels of pollution.

Studies on the impacts of pollutant metals and metalloids on livestock have largely focused on animals with relatively high levels of exposure. The impact of low-level environmental contamination, which is more common on agricultural land, is largely unknown. The principal aim of the present study was to examine the effects of low-level environmental contamination on trace metal metabolism in cattle from the rural and relatively uncontaminated region of Galicia (NW Spain). Correlations between toxic (cadmium, lead, and arsenic) and essential trace elements (copper and zinc) were evaluated in the tissues (liver, kidney, and muscle) and blood of 494 cattle from throughout Galicia. Cadmium was the toxic element that had the greatest influence on copper and zinc homeostasis. There was a significant positive association between renal cadmium and zinc residues and a significant negative correlation between kidney cadmium and copper. These interactions are likely to be the result of cadmium-induced effects on metallothionein synthesis. Lead and zinc were positively associated in the kidney, although the mechanism of this interaction is uncertain. Arsenic and copper concentrations were strongly correlated with each other in the liver and may indicate that the high copper levels in animals from copper-rich areas in Galicia interfere with their arsenic excretion. The essential metals copper and zinc were also significantly associated with each other in calves but not in cows.

Animals↗