Biomedical subjects

P García-Barreno

Publications and source records attributed to P García-Barreno.

At least 19 recordsLinked to original sources

PubMed2007

Effects of MDMA on blood glucose levels and brain glucose metabolism.

PURPOSE: This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. METHODS: Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated doses. Glucose metabolism was measured in 12 cerebral regions of interest. Rectal temperature and blood glucose were monitored. RESULTS: Peak body temperature was reached 1 h after MDMA administration. Blood glucose levels decreased significantly after MDMA administration. In the single-dose experiment, brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation in the hippocampus, amygdala and auditory cortex. In the repeated-dose experiment, brain glucose metabolism did not show any significant change at day 7. CONCLUSION: These results are the first to indicate that MDMA has the potential to produce significant hypoglycaemia. In addition, they show that MDMA alters glucose metabolism in components of the motor, limbic and somatosensory systems acutely but not on a long-term basis.

Adrenergic Uptake Inhibitors↗

PubMed2006

Peripheral leukocyte response to oncological radiotherapy: expression of heat shock proteins.

PURPOSE: To study Heat Shock Proteins (HSP) expression in patients subjected to radiotherapy and their potential use as biomarkers for radiation tolerance. An evaluation is also made of whether irradiated volume is critical to the outcome of normal tissue injury using polymorphonuclear neutrophils as biosensors, and whether HSP antibodies (Ab) may be involved in post-radiotherapy disease. MATERIAL AND METHODS: Twelve patients receiving the same total dose of radiotherapy, but in three different volumes, and four healthy volunteers used as controls were analysed. hsp27 and 70i mRNA were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and Southern-blot, HSP by flow cytometry, and HSP-Ab by Enzyme-linked Immnoadsorbent Assay (ELISA). The clinical protocol included radiation related toxicity based on clinical and analytical scales. RESULTS: Radiotherapy caused hsp downregulation, maximum in patients with the largest irradiated volumes, and a decrease in intracellular HSP content. Patients with greatest intraleukocyte HSP levels before treatment suffered more severe radiation morbidity. Patients with endocrine neoplasms presented the highest HSP-Ab titers. CONCLUSIONS: Radiotherapy downregulates hsp27 and 70i, which would enhance radiosensitivity. HSP content prior to treatment is suggested as a prognostic biomarker for radiation tolerance, with circulating leukocytes as biosensors. HSP-Ab may be biomarkers of tumor disease, but do not seem to be involved in the morbidity of acute post-radiotherapy disease, which is closely related to the volumes irradiated.

Aged↗

PubMed2003

Hydrodynamic and biochemical effects of isolated hypothermic renal perfusion depending on the pump model and perfusion solution.

OBJECTIVES: To evaluate hydrodynamic, biochemical, and histological consequences of hypothermic isolated renal perfusion using a new computerized perfusion system. MATERIALS AND METHODS: The device that allowed us to obtain on renal hydrodynamics during perfusion included multiple parts. The organ was perfused at 4 degrees C with a constant flow either using a classic roller pump or a pump designed in our laboratory to employ vacuum or atmospheric pressure sequentially to achieve a truly pulsatile wave (vacuum-powered tubular pump). The study included 16 minipigs with Eurocollins or Belzer perfusion solutions sampled at predefined interval and histological studies of the organs performed. RESULTS: There was a significant difference in weight increase between the two types of pumps; those perfused with Eurocollins showed greater values than those with Belzer solution. Onset of nitric oxide (NO) in the perfusion solution increased inversely with the renal vascular resistance. The highest NO levels were observed with the Belzer solution and vacuum pump. CONCLUSIONS: Changes in renal hydrodynamics, as induced by perfusion wave form and solution type, may be recorded in real time using a computerized system. A vacuum pump with the Belzer solution achieved the best experimental results.

Animals↗

PubMed2003

Influence of the normalization template on the outcome of statistical parametric mapping of PET scans.

Spatial normalization is an essential preprocessing step in statistical parametric mapping (SPM)-based analysis of PET scans. The standard template provided with the SPM99 software package was originally constructed using (15)O-H(2)O PET scans and is commonly applied regardless of the tracer actually used in the scans being analyzed. This work studies the effect of using three different normalization templates in the outcome of the statistical analysis of PET scans: (1) the standard SPM99 PET template; (2) an (18)F-FDG PET template, constructed by averaging PET scans previously normalized to the standard template; and (3) an MRI-aided (18)F-FDG PET template, constructed by averaging PET scans normalized according to the deformation parameters obtained from MRI scans. A strictly anatomical MRI normalization of each PET was used as a reference, under the rationale that a normalization based only upon MRI should provide higher spatial accuracy. The potential bias involved in the normalization process was estimated in a clinical SPM study comparing schizophrenic patients with control subjects. For each between-group comparison, three SPM maps were obtained, one for each template. To evaluate the influence of the template, these SPM maps were compared to the reference SPM map achieved using the anatomical normalization. SPMs obtained by MRI-aided normalization showed the highest spatial specificity, and also higher sensitivity when compared to the standard normalization using the SPM99 (15)O-H(2)O template. These results show that the use of the standard template under inappropriate conditions (different tracer or mental state) may lead to inconsistent interpretations of the statistical analysis.

Acute Disease↗

PubMed2003

Automatic quantification of viability in epithelial cell cultures by texture analysis.

Quantification of live cells in phase contrast microscopy images allows in vivo assessment of the viability of cultured cells. An automatic screening procedure seems advisable because of the large number of cells that must be counted to achieve reasonable accuracy. This paper presents a method that quantifies necrosis in cell cultures by texture analysis of microscope images. The image is divided into regions of equal size that are classified by means of a segmentation algorithm based on texture analysis into three categories: live cells, necrotic cells and background. The classification uses three discriminant functions, built from parameters derived from the histogram and the co-occurrence matrix and calculated by performing an initial stepwise discriminant analysis on 21 sample images from a training set. The areas occupied by live and necrotic cells and number of live cells have been obtained for primary cellular cultures in intervals of 48 h during 2 weeks. The results have been compared with those obtained by an experienced observer, showing a very good correlation (Pearson's coefficient 0.95, kappa 0.87, N= 1600). A method has been developed that provides an accuracy similar to that provided by an expert, while allowing a much higher number of fields to be counted.

Cell Culture Techniques↗

PubMed2002

Role of elastic fibers in cooling-induced relaxation.

The objective of this work was to confirm the main role of elastic fibers in differing responses of certain vessels during cooling from 37 to 8 degrees C. Previous results have shown that the nature of the vessel (conduit vessel vs muscular vessel) determines the different behavior (dilatation vs contraction) of isolated vessel segments when temperature decreases from 37 to 8 degrees C. In this work, it has been demonstrated that vessels with a great amount of elastic fibers show a dilatation when cooling. On the other hand, muscular vessels with fewer elastic fibers, such as the renal artery, undergo a contraction. The output of calcium from intracellular stores causes contraction of the renal artery during cooling. In this vessel, vasodilatation occurs only when mechanisms of smooth muscle contraction are inactive, as is the case with vessels that have undergone a cold storage period of 48 h. The results presented in this work confirm that there are two main effects, which directly depend on the vessel origin. In conduit arteries, the decrease of temperature induces a vascular relaxation, dependent on the elastic component of the vessel wall. In muscular vessels, the predominant effect is cooling-induced contraction due to an increase of intracellular calcium. This cooling-induced contraction needs the vessel to be in optimal conditions with an active metabolism of the muscular cells. These results are a crucial issue in the sense of explaining several biomedical mechanisms where hypothermia is implicated. The type of vessel implicated in procedures, such as isolated organ perfusion, extracorporeal circulation, and bypass surgery, must be taken into account.

Animals↗

PubMed2000

Paradoxical effects of temperature on vascular tone.

Temperature may have significant influence on vascular tone in such cases as organ preservation, coronary bypass surgery, and extracorporeal circulation. The aim of this research was to study the direct effect of temperature variation on vascular tone in an attempt to elucidate the mechanisms involved. In a first series of experiments, the isometric tension of two different vessels (rat thoracic aorta and pig renal branch artery) was studied at different temperatures. To study the role of calcium in this response, a second series of experiments was performed. In this the vessels were incubated with the intracellular chelator BAPTA/AM. Further experiments were performed to test the effect of cold storage. Our results show that changes in temperature lead to different results in pig renal artery and rat aorta. A decrease in temperature induced a highly reproducible relaxation in rat aorta, whereas pig renal artery presented cooling-induced contraction. Moreover, whereas calcium depletion failed to inhibit cooling-induced relaxation in rat aorta, it did not provoke cooling-induced contraction in pig renal artery. Similar responses were obtained with cold storage and calcium depletion. We intend to demonstrate that, just as the effect of temperature variation on pig renal artery is due to a metabolic mechanism, its effect on rat aorta may be due to structural factors. This hypothesis is supported by the result of histological studies which demonstrate a higher proportion of elastin fibres in rat aorta than in pig renal artery.

Animals↗

PubMed2000

Perfusate lactate dehydrogenase level and intrarenal resistance could not be adequate markers of perfusion quality during isolated kidney perfusion.

The main goal of this work was to study the influence of perfusion pressure and flow waveform during kidney perfusion, and the relationship between renal vascular resistance (RVR) and lactate dehydrogenase (LDH) concentration in the perfusate. Simultaneous constant pressure kidney perfusions were performed with either pulsatile or continuous flow at either 30 or 80 mm Hg of constant perfusion pressure. Mean flow, pressure, and RVR were displayed online during perfusion. Perfusate samples for LDH, creatine phosphatase kinase (CPK), and alkaline phosphatase (AP) determinations were taken. At the end of the perfusion, 2 ml of Evans blue was injected into the circuit to obtain images of perfusate distribution, and the kidneys were weighed. Also, hematoxylin/eosine studies were performed, showing more Bowman's space and tubular dilation in kidneys perfused with high pressure. We did not find differences in RVR between kidneys perfused at 30 and 80 mm Hg; nevertheless, perfusate distribution was better in the 80 mm Hg perfusions. We did not find any correlation between enzyme release and RVR in kidneys perfused with different mean pressures. These findings suggest that vascular resistance and LDH concentration cannot be independently considered as adequate markers of perfusate distribution.

Alkaline Phosphatase↗

PubMed1998

Isolated kidney controlled perfusion with true physiological pulsatile waveform.

A computer controlled perfusion system has been developed to study the behavior of perfused kidneys in several conditions. The system is designed to perform kidney perfusions at constant pressure and low temperature (about 4 degrees C). We compared 2 types of perfusion pumps, a classical roller pump widely used in hemodialysis circuits and a vacuum powered tubular pump with active valves developed by our group and able to produce a flow pattern very similar to the pulse wave in the human circulatory system. In this preliminary study, we show the hydrodynamics obtained with both pumps in isolated hypothermic kidneys perfused with this system. The different flow patterns with both pumps seem to determine differences in the preservation conditions of the kidney.

Animals↗

PubMed1998

[Integration of multimodal medical images].

Multimodality analysis is becoming a required tool in medical practice due to the development of different image techniques and new imaging processing tools. This paper is a review of the basis of medical image integration, image fusion techniques, and their clinical applications, especially addressing our experience with brain tomographic studies in nuclear medicine and radiology.

Algorithms↗

PubMed1997

Simulated surgery on computed tomography and magnetic resonance images: an aid for intraoperative radiotherapy.

Intraoperative radiotherapy (IORT) is a relatively new technique in which irradiation with electrons is performed during an open surgery procedure. This approach poses significant problems in obtaining accurate dosimetry, since neither the pre- nor the postoperative patient images actually matches the irradiation field. Our objective was to implement a software tool able to provide an estimate of the dose distribution, overcoming the problem of the geometrical mismatch between the images and the surgical field during the irradiation. The program was developed in the C programming language, on a noncommercial version of a Philips EasyVision workstation. The application allows to create a new data set by manipulating the preoperative computed tomography and magnetic resonance images in order to simulate the final geometry of the surgical area during the IORT procedure. The exact dose distribution can then be calculated by transferring these new images to a standard radiotherapy planning system. Also an approximate dose distribution can be quickly displayed by superimposing isodose curves obtained from a water phantom. The proposed approach introduces a helpful tool for dosimetry and planning in IORT protocols, improving their accuracy and safety and allowing for more objective quality control and patient follow-up.

Brain Neoplasms↗

PubMed1996

Levels and activity of brain protein kinase C alpha and zeta during the aging of the medfly.

Brain protein kinase C (PKC) activity, as well as PKC alpha and PKC zeta levels detected by immunoblotting, were monitored during the lifespan of the Mediterranean fruit-fly Ceratitis capitata. PKC activity increased in the particulate fraction during the last stages of the life of C. capitata. Immunoblotting studies with an anti-PKC alpha antibody also demonstrated increased enzyme levels in the particulate fraction. Cytosolic levels of PKC zeta decreased in the terminal phase of the lifespan of the fly, whereas levels of membrane-bound PKC zeta increased at that stage. Results thus indicate that during C. capitata final phase of life a translocation of PKC alpha and PKC zeta to the particulate fraction occurs, and therefore both kinases could be involved in the terminal process of this fruit-fly.

Aging↗

PubMed1996

Tubular vacuum-powered blood-pumping device with active valves.

We propose a new vacuum-driven blood pump having a tubular shape with active valves. This design avoids any possible problems caused by membrane breakage, thereby minimizing the risk of gas embolic events and stagnation regions. By using active valves, it is possible to ensure better flow control and minimize pressure gradients inside and outside the pump. The low cost of the pump's disposable parts enables it to be used for such applications as a ventricular assist device, a pulsatile pump device in extracorporeal circulation, a pump in hemodialysis and apheresis circuits, and a pump in extracorporeal membrane oxygenator systems.

Equipment Design↗

PubMed1993

Cardiac beta-adrenoceptors, G-proteins and adenylate cyclase regulation during myocardial hypertrophy.

The role of the beta-adrenoceptor-G-protein-adenylate cyclase system in the pathogenesis of cardiac hypertrophy was studied. We have used a minipig model of pressure-overload cardiac hypertrophy secondary to aortic banding. Four groups of five animals were used: minipigs made hypertrophic were evaluated 2 months (CH2 group) and 9 months (CH9 group) later and compared to controls (C2 and C9 groups, respectively). A decrease in beta-adrenergic receptor density and an increase in antagonist affinity were shown in left ventricular membranes of hypertrophied animals compared with controls. In both groups, CH2 and CH9, an increase in EC50 for isoproterenol-stimulated adenylate cyclase activity, an increase in forskolin-stimulated adenylate cyclase activity and a diminished inhibition by carbachol of isoproterenol-stimulated adenylate cyclase were observed. In contrast, fluoride-stimulated adenylate cyclase activity was markedly increased only in the end stage of hypertrophy. alpha s-cholera toxin-catalysed ADP-ribosylation is increased in early hypertrophy and then decreases with late hypertrophy and a similar pattern is observed with alpha o pertussis toxin-catalysed ADP-ribosylation, whereas alpha i-ADP-ribosylation remains unchanged. Tissue content of Gs-, Gi- and Go-proteins, as assessed by specific antibodies, was found unchanged in CH9 and CH2 groups when compared with that in C9 and C2 control groups, respectively. Modifications in Gs functional activity in later hypertrophic stages, expressed as alterations in cholera toxin ADP-ribosylation and adenylate cyclase fluoride responsiveness, may be important in the pathogenesis of decompensation from compensated hypertrophy to cardiac failure.

Adenylate Cyclase Toxin↗

PubMed1992

Improvement of the hydrodynamic response of a ventricular assist device: a false auricle solution.

We propose a new design of the auricular cannula in ventricular assist devices (VADs), consisting of a collapsible large cannula with a capacity approximately equal to the ejection volume of the VAD. The device works as a false auricle and filters the negative pressure that occurs during diastole. We show that the use of this type of cannula improves the hydrodynamic efficiency and the stability of the working conditions. Moreover, during chronic implantation in sheep, hemolysis stays well below pathological levels. These improvements result in much better controllability of the whole VAD.

Animals↗

PubMed1989

Blood biochemistry values of sheep (Ovis aries ligeriensis).

1. Analysis of biochemical parameters were carried out on material pooled from 30 female sheep (Ovis aries ligeriensis). 2. The values determined were for the common metabolites and enzymes utilized for specific studies in general metabolism (urea, glucose, cholesterol, lipids, bilirubin, uric acid, creatinine, alkaline phosphatase, GOT, GPT, LDH, LAP, CGT, CK and amylase). 3. Results of these studies were compared with values from normal human adults. 4. The differences obtained in human and sheep ranges can be explained by the different physiology of the two species. 5. This study gives values for the sheep as an experimental animal in biomedical research.

Animals↗

PubMed1988

Modification of catecholamine and prostaglandin tissue levels in E. coli endotoxin-treated rats.

Epinephrine and norepinephrine adrenal levels were depleted in Escherichia coli endotoxin-treated (10 mg/kg) male Wistar rats from 504 +/- 203 to 119 +/- 77 ng/mg in control and from 200 +/- 97 to 123 +/- 66 ng/mg wet wt, respectively. However dopamine increased from 4.2 +/- 1.9 to 14.9 +/- 3.4 ng/mg. After endotoxin administration, norepinephrine content in peripheral organs, heart 1.27 +/- 0.19 ng/mg, spleen 1.52 +/- 0.59 ng/mg, liver 0.15 +/- 0.05 ng/mg, and kidney 0.24 +/- 0.09 ng/mg wet wt. decreased by 34, 36, 47, and 18%, respectively. Indomethacin treatment kept the catecholamine levels constant in endotoxic rats, but naloxone had no effect. PGF2 alpha tissue levels (12.0 +/- 10.1 pg/mg protein in spleen and 1.85 +/- 0.6 pg/mg protein in liver) were increased twofold by endotoxin treatment: PGE2 content in spleen and liver 0.5 +/- 0.2 pg/mg protein and 2.3 +/- 1.9 pg/mg protein, respectively, increased by only 27 and 26%. In the kidneys of endotoxin-treated animals, PGF2 alpha and PGE2 levels were lower than in control. Indomethacin treatment decreased PGF2 alpha and PGE2 and increased the norepinephrine content in the same organs. It is suggested that prostaglandins play a participative role in the control of norepinephrine tissue levels in endotoxemia.

Adrenal Glands↗

PubMed1988

Endothelial cell growth factor and ionophore A23187 stimulation of production of inositol phosphates in porcine aorta endothelial cells.

The existence of a bovine brain-derived endothelial cell growth factor has recently been reported, but its mode of action is unknown. We show that the endothelial cell growth factor is a potent stimulant of inositol monophosphate release in porcine aorta endothelial cells. Although the activation of phospholipase C by this factor does not appear to be dependent on Ca2+, the Ca2+ ionophore A23187 stimulates release of inositol phosphates. It is suggested that the inositol 1,4,5-trisphosphate 3-kinase/5-phosphomonoesterase pathway could account for the ionophore-induced changes in inositol 1,3,4-triphosphate.

Animals↗