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Biomedical subjects

E De Miguel

Publications and source records attributed to E De Miguel.

At least 19 recordsLinked to original sources

Risk-based evaluation of the exposure of children to trace elements in playgrounds in Madrid (Spain).

Eighty samples of sandy substrate were collected in November 2002 and 2003, from 20 municipal playgrounds in Madrid (Spain) to assess the potential adverse health effects of the exposure of children to trace elements in this material during their games. In each playground, two 500 g samples were collected, dried at 45 degrees C for 48 h, sieved below 100 microm, acid digested and analyzed by ICP-MS. Doses contacted through ingestion and inhalation and the dose absorbed through the skin were calculated using USEPAs hourly exposure parameters for children and the results of an in situ survey. The toxicity values considered in this study were mostly taken from the US DoEs RAIS compilation. The results of the risk assessment indicate that the highest risk is associated with ingestion of soil particles and that the trace element of most concern is arsenic, the exposure to which results in a cancer risk value of 4.19 x 10(-6), close to the 1 x 10(-5) probability level deemed unacceptable by most regulatory agencies. Regarding non-cancer effects, exposure to playground substrate yields an aggregate Hazard Index of 0.28, below the threshold value of 1 (with As, again, as the largest single contributor, followed by Pb, Cr, Al and Mn). Although the uncertainties associated with the estimates of toxicity values and exposure factors should be reduced before any definite conclusions regarding potential health effects are drawn, risk assessment has proven to be a very useful tool to identify the contaminants and exposure pathways of most concern in urban environments.

Environmental Exposure↗

Assessing the intra- and inter-reader reliability of dynamic ultrasound images in power Doppler ultrasonography.

OBJECTIVE: To assess the intra-reader and inter-reader reliabilities of interpreting ultrasonography by several experts using video clips. METHOD: 99 video clips of healthy and rheumatic joints were recorded and delivered to 17 physician sonographers in two rounds. The intra-reader and inter-reader reliabilities of interpreting the ultrasound results were calculated using a dichotomous system (normal/abnormal) and a graded semiquantitative scoring system. RESULTS: The video reading method worked well. 70% of the readers could classify at least 70% of the cases correctly as normal or abnormal. The distribution of readers answering correctly was wide. The most difficult joints to assess were the elbow, wrist, metacarpophalangeal (MCP) and knee joints. The intra-reader and inter-reader agreements on interpreting dynamic ultrasound images as normal or abnormal, as well as detecting and scoring a Doppler signal were moderate to good (kappa = 0.52-0.82). CONCLUSIONS: Dynamic image assessment (video clips) can be used as an alternative method in ultrasonography reliability studies. The intra-reader and inter-reader reliabilities of ultrasonography in dynamic image reading are acceptable, but more definitions and training are needed to improve sonographic reproducibility.

Arthritis↗

Enriched protein diet-modified ghrelin expression and secretion in rats.

Gastrointestinal (GI) integrity and function are regulated by nutrition and growth factors. The discovery of ghrelin, a natural growth hormone (GH) secretagogue produced by the gastrointestinal (GI) tract, is a potential link between diet and growth signals. The aim of this study was to evaluate macronutrient effect on ghrelin expression and secretion in addition to some possible function in intestinal trophic status. Wistar rats were fed a high-carbohydrate, high-protein (HP), high-fat or standard (St) diet. Animals received the same daily food volume and caloric intake. After 7 days, animals were fasted for 24 h and blood and tissue samples were obtained just before feeding or at 2 or 6 h after feeding. Fasting high-protein-fed rats had higher ghrelin plasma levels than with rats fed the high-carbohydrate, high-fat or standard diets. Two-hours after refeeding, ghrelin plasma levels had decreased in all groups with a slight recovery at 6 h after refeeding, except in the high-protein group. Ghrelin plasma levels in rats fed with the high-protein diet correlated negatively with their GH and insulin-like growth factor 1 (IGF-1) plasma concentrations which were also the lowest among the study groups. In conclusion, ghrelin secretion was nutritionally manipulated because a protein-enriched diet increased its levels.

Animals↗

Chronic nicotine administration increases NGF-like immunoreactivity in frontoparietal cerebral cortex.

Nicotine/nicotine agonists, which have been proposed as therapeutic agents for the treatment of Alzheimer's disease and other neurodegenerative disorders, produce a wide variety of effects on the nervous system. Some mechanisms involved remain poorly understood. In this work, immunohistochemical techniques were used to determine the effect of nicotine on nerve growth factor (NGF) in the frontoparietal (motor, somatosensory) brain cortex of the albino rat. Nicotine was chronically administered intraperitoneally using osmotic pumps (0.35 mg nicotine base/kg body weight/day for 14 days). An increase in the number and the immunoreaction intensity of NGF-like positive pyramidal and nonpyramidal neurons of these cortical areas was observed after treatment. Immunopositive astroglial cells were always seen in sections of treated animals but not in controls. The neuropil of control animals was, in general, devoid of reaction, but in treated animals, immunopositive prolongations were located randomly, some in close association with capillaries. At the electron microscopic level, these prolongations were demonstrated as belonging to neurons (dendrites and axons) and astroglial cells. Nicotinic activation of selected neurons and glial cells seems to trigger NGF/neurotrophic mechanisms, suggesting their use may be of benefit in prevention and treatment of neurodegenerative diseases.

Animals↗

Distribution of heavy metals in the street dusts and soils of an industrial city in northern Spain.

This study characterizes the elemental composition of street dust and soils in Avilés (N. Spain), a medium-size city of approximately eighty thousand inhabitants, where industrial activities and traffic strongly affect heavy metal distribution. A total of 112 samples of street dust were collected within a 7-km(2) area, encompassing residential and industrial sites (ferrous and non-ferrous plants). Elevated geometric mean concentrations of zinc (4,892 microg x g(-1)), cadmium (22.3 microg x g(-1)), and mercury (2.56 microg x g(-1)) in street dust were found in samples located near industrial areas. Two types of anthropic influence were distinguishable: the first and most important one is that related to metallurgical activity and transportation of raw materials for local industries. Secondly, exhaust emissions from traffic are an important source of lead concentration in areas with high vehicular density (geometric mean: 514 microg x g(-1)). The zinc content in the dust samples decreased with the distance from a zinc smelter located in the northern part of the city. The same trend was found for other elements in association with zinc in the raw materials used by the smelter, such as cadmium and mercury. A simultaneous research campaign of urban soils, that involved the collection of 40 samples from a 10-km(2) area, revealed geometric mean concentrations of 376 microg x g(-1) Zn, 2.16 microg x g(-1) Cd, 0.57 microg x g(-1) Hg, and 149 microg x g(-1) Pb, and distribution patterns almost identical to those found for street dust.

Cities↗

Influence of industry on the geochemical urban environment of Mieres (Spain) and associated health risk.

This study is concerned with the elemental composition of soils and street dust collected in an historical industrial city of approximately 27,000 inhabitants, where old Hg mining and metallurgical activities strongly affected the load of heavy metals in the urban environment. For the purpose of the study, representative samples of soils and street dust were collected at different locations in the whole urban area (3 km2). Elevated mean concentrations of As in soils and street dust (69 and 135 micrograms g-1, respectively), and Hg (3.07 and 4.24 micrograms g-1, respectively), compared to background levels and to those found in other cities, reflect the anomalous geochemical nature of these materials and the strong influence exerted by the old mining sites.

Arsenic↗

Electrophysiologic cardiac effects of the new local anesthetic IQB-9302 and of bupivacaine in the anesthetised dog.

BACKGROUND: Local anesthetics are not free from potentially fatal complications. Therefore every new local anesthetic should be tested to demonstrate a lower, or at least similar, degree of toxicity over clinically used analogs. Most toxic effects from local anesthetics affect the cardiac electrophysiologic function, so the aim of this study was to characterize the electrophysiologic effects of a new long-acting local anesthetic (IQB-9302, Ciprocaine), and compare them with those of bupivacaine in the anesthetized dog. METHODS: Eight Beagle dogs received three increasing infusion doses of either IQB-9302 or bupivacaine. Under isoflurane anesthesia, dogs were instrumented to monitor cardiovascular (cardiac output, arterial and venous blood pressures) and cardiac electrophysiologic data (sinus and atrioventricular (AV) node function, atrial, nodal and ventricular conduction times, and refractoriness). RESULTS: Only the highest dose of both drugs induced hemodynamic or electrophysiologic alterations: cardiac output and heart rate were reduced while blood pressures remained unchanged. Atrial and intranodal conduction times and atrial refractoriness increased similarly with both anesthetics, but to a slightly lesser extent with IQB-9302. Significant increases in His-Purkinje and intraventricular conduction times were the most severe noxious effects and occurred only with large doses of either drug. IQB-9302 was slightly less toxic than bupivacaine and, unlike this latter drug, potentially fatal arrhythmias were not induced. CONCLUSION: IQB-9302 has hemodynamic and cardiac electrophysiologic effects similar to those caused by bupivacaine. Nevertheless, slightly less toxic effects were derived from IQB-9302 administration than with bupivacaine, and, unlike the latter, the former might be less proarrhytmogenic. The new long-acting local anesthetic IQB-9302 may offer clinical advantages compared with bupivacaine.

Anesthetics, Inhalation↗

Painful shoulder: comparison of physical examination and ultrasonographic findings.

BACKGROUND: High frequency ultrasonography is an accurate non-invasive imaging technique for evaluating patients with painful shoulder. OBJECTIVE: To compare the clinical diagnosis established by a physical examination with high frequency ultrasonographic findings in patients with painful shoulder. METHODS: Thirty one consecutive patients with a first flare of shoulder pain were prospectively included in the study. All had a physical examination performed by two blinded rheumatologists. Ultrasonographic examination was carried out within one week of the physical examination by a third rheumatologist experienced in this technique who had no knowledge of the clinical findings. Ultrasonography was considered the optimal diagnostic technique. RESULTS: Clinical assessment showed low accuracy in the diagnosis of periarticular shoulder lesions. CONCLUSION: Ultrasonography should be used wherever possible to improve diagnosis and treatment of painful shoulder.

Adult↗

Histochemical study of acute and chronic intraperitoneal nicotine effects on several glycolytic and Krebs cycle dehydrogenase activities in the frontoparietal cortex and subcortical nuclei of the rat brain.

The effects of nicotine on the activity of different dehydrogenases in frontoparietal regions and subcortical nuclei of the rat brain have been studied using histochemical methods. Nicotine sulphate was intraperitoneally administered in acute (4 mg/kg/day x 3 days) or chronic (ALZET osmotic pump providing 2 mg/kg/day x 15 days) doses. The enzymes analyzed were glyceraldehyde-3-phosphate, lactate, malate and succinate dehydrogenases (gly3PDH, LDH, MDH, and SDH, respectively). The results demonstrate that chronic as well as acute administration of nicotine produced strong increases in all these enzymatic activities in the superior layers (I, II and III) of the frontoparietal cortex (cingulate, motor and somatosensory regions); but high increases were not seen in the deeper layers of the cortex or in the subcortical nuclei (substantia nigra, caudate-putamen, nucleus accumbens or nucleus basalis magnocellularis). These hyperactivities were produced in brain regions with normally low enzymatic activity (cortex), but not in those with great intensity (subcortical nuclei). The results are in rough agreement with previous reports on nicotine-induced increases in glucose utilization, gly3PDH genic expression and neuronal hyperactivity in the brain cortex; but significant discrepancies between the cortical enzymatic maps and those obtained both in these studies and others on nicotine(N)-receptor localization have been appreciated. The results support the hypothesis that nicotinic cholinergic drugs can have metabolic, long-lasting stimulant effects on cortical neurons at specific points (probably layer III pyramidal cells and structures with alpha7-N-receptors) of the cortical circuits that could be of great interest in improving altered cognitive functions that are present in Alzheimer disease, as well as in other less severe mental disturbances. Mitochondrial hyperfunction should also be evaluated as a possible side-effect (as an oxidative stress inductor) of these kinds of drugs.

Animals↗

Growth hormone plus high protein diet promotes adaptation after massive bowel resection in aged rats.

OBJECTIVE: To determine whether GH improves adaptation following massive bowel resection in the aged rat fed on a high protein-content diet. MATERIAL AND METHODS: Seventy-seven male Wistar rats aged 22+/-1 months underwent 80% bowel resection or laparotomy (sham-operation). They were randomly placed into one of eight groups, treated with either growth hormone (1mg/kg/day) or saline, and fed a liquid diet containing either a high or a normal protein content. Intestinal tissue and blood samples were taken seven days after surgery and analysed to measure intestinal mucosal proliferation and mucosal height, as well as plasma levels of IGF-1 and somatostatin. RESULTS: Resection of the small bowel in aged rats remarkably increased villous height and crypt proliferation. Growth hormone did not potentiate the increase in mucosal height and crypt proliferation observed after intestinal resection in aged rats fed a normal protein content diet, but did in those receiving a high-protein diet. Plasma levels of IGF-1 and somatostatin were not modified by surgery or treatment. CONCLUSION: Growth hormone may increase the adaptation of intestinal mucosa in aged rats undergoing massive intestinal resection, but requires an adequate nutritional support with increased amounts of high quality protein.

Adaptation, Physiological↗

Somatostatin antagonism prevents elemental diet-induced intestinal atrophy in the rat.

Somatostatin is a peptide with known antiproliferative effects on the intestine. The aim of the present work was to determine whether somatostatin (SST) antagonism reduces elemental diet-induced intestinal atrophy in the rat. Male Wistar rats were fed a standard diet and treated for seven days with either continuous infusion of saline or low and high doses of a putative somatostatin antagonist; another group was given a SST antagonist in a pulsatile high dose. All these groups received an elemental diet to induce gut mucosa atrophy. Rats were killed and samples were obtained for morphometric and proliferative measurements of the intestine and for SST and insulin-like growth factor-1 (IGF-1) level determination. The elemental diet decreased mucosal length and proliferation. Pulsatile administration of SST antagonist improved or prevented both effects, whereas continuous SST antagonist delivery prevented decreased crypt proliferation induced by the elemental diet. Somatostatin plasma levels were lowest in rats receiving pulsatile administration of SST antagonist. In conclusion, somatostatin antagonism increases proliferation in the intestinal mucosa, improving elemental diet-induced intestinal atrophy; however, morphological growth is not affected.

Adaptation, Physiological↗

Somatostatin blockade improves the proliferative response but not intestinal morphological growth after small bowel resection in rats.

OBJECTIVE: To find out whether or not blockade of somatostatin improves intestinal adaptation after small bowel resection. DESIGN: Laboratory experiment. SETTING: Teaching hospital, Spain. SUBJECTS: Eighty adult Wistar rats. INTERVENTIONS: Animals underwent intestinal resection or sham operation (n = 40 each) and were treated with a somatostatin antagonist either intermittently or continuously in three different doses (n = 8 each). MAIN OUTCOME MEASURES: Bowel mucosal thickness, proliferation and concentrations of cAMP, somatostatin, insulin-like growth factor 1. RESULTS: Intestinal resection induced a proliferative and morphometric increase of the mucosa; however, the antagonist increased proliferation only in those animals given the highest dose. Intermittent doses induced a proliferative effect that was stronger than that in the three continuous groups. There was no relationship between trophic stimulus and insulin-like growth factor 1 or cAMP, but somatostatin concentrations increased after the intermittent course. CONCLUSIONS: Somatostatin receptor blockade with an antagonist does not cause in normal rats an intestinal morphological adaptation process or increase it after resection; however, it did promote a proliferative stimulus in the crypts.

Animals↗

Growth hormone effects in intestinal adaptation after massive bowel resection in the suckling rat.

BACKGROUND: Massive small bowel resection provokes intestinal malabsorption that leads to diminished growth in the suckling rat. Growth hormone is one of the several factors that can enhance the adaptive response of the intestines in the adult rat; however, whether it also enhances postresection intestinal adaptation in the suckling rat, thus reducing the adverse effects of resection on growth, is still unclear. METHODS: Seventy-four 30-day-old suckling Wistar rats underwent 80% midgut bowel resection, laparotomy (sham operation), or no surgery. They were treated with either growth hormone or saline for 15 days and studied 15 or 45 days after surgery. Body weight was monitored and samples of bone and intestinal mucosa were obtained at the end of the study period for analysis. RESULTS: Resected rats lost body and bone weight regardless of growth hormone administration. Bowel resection provoked significant increases in the proliferation and size of the intestinal mucosa. Growth hormone significantly, but just barely, increased crypt height and mucosal mass at day 15 after surgery, but not at day 45. Lengthening of the intestines was the main effect of growth hormone. CONCLUSIONS: The relatively small adaptive response of intestines to growth hormone is insufficient to promote body growth after intestinal resection in the suckling rat. This response is lower than that in older rats and may reflect an age-related differential response to growth hormone.

Adaptation, Physiological↗

Growth hormone and nutrition as protective agents against methotrexate induced enteritis.

OBJECTIVE: To determine whether exogenously administered growth hormone can reduce or prevent chemotherapy-induced intestinal mucosa injury. The expected results will allow to consider its potential clinical use. DESIGN: Experimental and randomized study. SETTING: Experimental Surgery Service, La Paz University Hospital. SUBJECTS: Adult Wistar rats weighing 250-300 g. MATERIALS AND METHODS: A chemotherapy protocol with methotrexate (MTX) (120 mg/kg) was employed. Animals fed either with a normoproteic or a hyperproteic liquid diet were treated with either saline or growth hormone (1 mg/kg/day) since three days before until four days after chemotherapy. Animals were sacrificed seven days after MTX administration for tissue sampling. RESULTS: Co-administration of growth hormone and a hyperproteic diet increased intestinal crypt proliferation and reduced MTX-induced apoptosis. CONCLUSIONS: Jejunal mucosal structure (morphometry), proliferation (Ki-67) and apoptosis (TUNNEL) were assessed.

Animals↗

Localization of glyoxylate dehydrogenase and glyoxylate-complex molecules in the rat prefrontal cortex: enzymohistochemical and immunocytochemical study.

Glyoxylic acid is synthesized and catabolized in cells of vertebrates; several pathways have been described. In previous papers, we have demonstrated the localization in some areas of the rat cerebral cortex both of beta-NAD-dependent glyoxylate dehydrogenase (glyoDH), using an enzymohistochemical method, and of glyoxylate-complex molecules, using immunocytochemical procedures. In this study we have applied these two techniques in various areas of the prefrontal cortex with different histological cytoarchitecture. GlyoDH has been located in most neurons, in some glial cells, and in capillary wall structures in all cortical layers of all areas of the rat prefrontal cortex. Antibodies against glyoxylate-complex molecules showed positive immunoreactivity in scattered neurons, mostly of multipolar or stellate appearance, from layers III, IV, and V in the medial precentral area, but not in cortical areas 24, 25, or 32 of the prefrontal cortex. Immunoreaction was found in the periphery of neuronal perikarya and in some of their processes. These results demonstrate the existence of a particular area-dependent neuronal cortical system, of specific but uncertain function, related to glyoxylic acid and/or glyoxylate compounds. At the electron microscope level, positive reaction was associated with synaptic sites, axonal filaments, glial cells, and several components of the blood-brain barrier. These localizations suggest the involvement of glyoxylate derivatives in synaptic functioning and also in glial cell functions.

Aldehyde Oxidoreductases↗

The distribution of two different vitamin D receptor polymorphisms (BsmI and start codon) in primary hyperparathyroidism.

INTRODUCTION: The bb genotype of the BsmI polymorphism of the vitamin D receptor (VDR) is more common in primary hyperparathyroidism (HPT) than in the general population in Swedish and German women. However, little is known about the association of HPT with the start codon polymorphism of the VDR (defined by FokI). OBJECTIVE: To study the distribution of the VDR genotypes in a group of women with HPT compared with a control group. The bone mineral density (BMD) of different genotypes was also investigated. METHODS: VDR alleles were typed by polymerase chain reaction (PCR) assay around the polymorphic BsmI or FokI restriction sites in 67 control women (48.5 +/- 10 years) and 53 women with HPT (61.4 +/- 11 years). They were all Caucasian and born in the Canary Islands. Lumbar and proximal femur BMDs were measured by dual X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). RESULTS: The 'bb' genotype was equally frequent in controls and HPT subjects (46.3 and 45.3%, respectively). There was a trend towards a lower prevalence of the FF genotype amongst women with HPT as compared with controls (41.5 vs. 57.1%; P = 0.09). BMD was lower in patients with HPT compared with controls in the lumbar spine and the proximal femur. CONCLUSIONS: The association of the BsmI polymorphism of the VDR gene with HPT is not applicable to all geographical areas. In Canarian postmenopausal women suffering from HPT, VDR genotype distribution is similar to that found in controls. A possible association of HPT with the FokI polymorphism deserves further investigation.

Aged↗

Increased plasma levels of homocysteine and other thiol compounds in rheumatoid arthritis women.

OBJECTIVES: Since moderate hyperhomocysteinemia is an independent risk factor for vascular disease and physiological thiol compounds mediate Cu2+- and Fe3+-dependent low-density lipoprotein (LDL) oxidation, we have studied the total plasma concentrations of thiol compounds including methionine as precursor of homocysteine in rheumatoid arthritis patients, in which the high mortality found is associated with cardiovascular disease. DESIGN AND METHODS: Thirty-eight women with rheumatoid arthritis and 25 age-matched control women were studied. Plasma was used to measure thiol compounds and amino acids by HPLC. RESULTS: Rheumatoid arthritis patients showed significantly higher levels than healthy controls of total plasma homocysteine (17.3 +/- 7.8 vs. 7.6 +/- 1.9; p <0.001), cysteine (293 +/- 61 vs. 201 +/- 45; p < 0.001), cysteinglycine (32.7 +/- 8.3 vs. 22.3 +/- 4.7; p < 0.001) and methionine (25 +/- 9 vs. 18 +/- 3; p < 0.01), whereas total glutathione levels were not increased (4.7 +/- 2.0 vs. 4.1 +/- 1.6). CONCLUSIONS: The increased levels of thiol compounds found in rheumatoid. arthritis patients may be implicated in the increased incidence of cardiovascular disease found in these patients by means of the toxic effect of homocysteine on endothelium and the increased susceptibility of LDL to oxidation by increased plasma amounts of thiol compounds such as cysteine.

Adult↗

Lung transplantation from ventilated non-heart-beating donors: experimental study in a neonatal swine model.

BACKGROUND/PURPOSE: A shortage of transplantable lungs is a constant and frustrating reality. The use of organs retrieved from ventilated non-heart-beating donors (VNHBD) may alleviate this problem. The purpose of this work was to assess lung function of donor grafts subjected to different time lengths of in situ warm ischemia (WIT). METHODS: Twenty piglets weighing between 6 and 8 kg were allocated randomly to the following study groups: Sham (n = 5), heart-beating donors, non warm ischemia; I-30 (n = 5), I-60 (n = 5) and I-90 (n = 5), VNHBD-WIT of 30, 60, and 90 minutes, respectively. Recipients were rendered dependent on the single left transplanted lung by clamping right pulmonary artery and bronchus 1 hour after transplantation. Assessment of pulmonary function was monitored hourly by hemodynamic, oxygenation, and pulmonary mechanic measurements during a period of 6 hours after reperfusion. Lung grafts were weighed pre- and posttransplantation. RESULTS: Final mean lung weight was significantly greater in VNHBD (92.5+/-3.1 v Sham values 75.6 g+/-2.4; P < .01). Cold ischemic time averaged 80.1+/-2.7 minutes. After right lung exclusion, hemodynamic changes consisted of a sustained increase in pulmonary vascular resistance and a reduction in cardiac output. Lung mechanics also deteriorated with a gradual rise in airway resistance and a fall in compliance. CONCLUSIONS: These data suggest that posttransplantation lung graft function from VNHBD with up to 90 minutes of WIT, is preserved and equivalent to those achieved by grafts harvested after heart-beating donation.

Analysis of Variance↗