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Biomedical subjects

V Martínez

Publications and source records attributed to V Martínez.

At least 19 recordsLinked to original sources

Susceptibility and exposure biomarkers in people exposed to PAHs from diesel exhaust.

Xenobiotic metabolizing enzymes, especially CYP1A1 and GSTM1, are involved in the activation and conjugation of PAHs and are controlled by polymorphic genes. PAHs released from diesel emissions in many cities of the world, especially in developing countries, contribute significantly to the toxic effects of airborne inhalable particles. We have evaluated the gene-environment interaction in Santiago of Chile, studying the contribution of CYP1A1 and GSTM1 polymorphisms on 1-OH-P urinary levels used as the PAHs exposure biomarker. The study was performed on 59 diesel exposed (38 diesel revision workers and 21 subjects working in an urban area as established street vendors) and 44 non-exposed subjects living in a rural area. The 1-OH-P urinary levels of the urban (P=0.043) and rural (P=0.040) populations showed, without considering the genotypes, significant differences between smokers and non-smokers, but no significant differences were found between smokers and non-smokers among the diesel plant workers (P=0.33). Non-smoking subjects of the diesel plants and the urban area showed similar 1-OHP levels (P=0.466) which were significantly higher than those of the subjects living in the rural area (P<0.05). When 1-OH-P levels were related with genotypes, an association was observed for the CYP1A1*2A genotype, so that the diesel-exposed workers carrying the CYP1A1*2A allele showed significantly higher 1-OH-P levels than the subjects from the rural area with the same genotype (P=0.008). On the other hand, there was no significant correlation between urinary 1-OH-P levels and GSTM1 null genotype, although higher levels of the urinary metabolite were found in individuals carrying the combined CYP1A1*2A and GSTM1 null genotype (P=0.055). These results may suggest an association between levels of the exposure biomarker 1-OH-P and presence of the CYP1A1*2A genotype, a potential genetic susceptibility biomarker which might be useful in identifying individuals at higher risk among people exposed to high PAH levels in diesel exhaust.

Adult↗

Gastric hypersecretion associated to iodoacetamide-induced mild gastritis in mice.

Disturbances of gastric motor, secretory and/or sensory functions are frequently associated with gastritis. The aim of this study was to characterize motor and secretory alterations associated to chemically-induced gastritis in mice. Mild gastritis was induced with 0.1% iodoacetamide administered intragastrically and added to the drinking water for a 6 days period. A significant loss of body weight and a reduction in food and water intake was observed in iodoacetamide-treated animals compared with those receiving vehicle. At the end of the treatment period, no macroscopic alterations were observed in the gastric mucosa of iodoacetamide-treated mice. However, histological sections revealed a mixed inflammatory infiltrate, with a predominance of mast cells in the submucosa; suggesting a mild gastritis. Gastric emptying rate of a nutrient solid meal was not modified in mice with gastritis compared with normal controls. In animals with gastritis, basal gastric acid secretion was increased compared with normal controls. Basal gastric acid secretion was not modified by either indomethacin or compound 48/80. Secretory response to secretagogues (pentagastrin and histamine) was enhanced during gastritis. Hypersecretory responses to both gastrin and histamine in iodoacetamide-treated mice were blocked by the mast cell stabilizer sodium cromoglycate, and enhanced by indomethacin, without affecting the secretory response in normal mice. These results suggest that mild gastritis alters gastric acid secretory responses through a mechanism related, at least partially, to mast cells activation. Moreover, prostaglandins also modulate secretory responses during mild inflammation. This animal model of gastritis might be useful to characterize pathophysiological changes and potential therapeutic targets in secretory-related gastric pathologies.

Animals↗

[Clinical risk factors for postoperative proliferative vitreoretinopathy (PVR). A prospective study].

PURPOSE: To identify clinical risk factors for development of postoperative PVR, to determine the incidence of this complication and its time of onset by a prospective multicentric study. METHODS: A multicentric and prospective study of 223 patients with rhegmatogenous retinal detachment (RD) was conducted. Logistic regression analysis was used to identify risk factors for PVR among 83 variables related to preoperative, intraoperative and postoperative characteristics. RESULTS: 22 out of 223 RD developed PVR (incidence 9.9%, confidence interval 95%: 5.9-13.9). After logistic regression analysis, four variables showed an odds ratio higher than 1.0 (RD affecting 4 quadrants, cryopexy, aphakia/pseudophakia and those RD in which an encircling band was implanted). None of these factors showed a < > value lower than 0.05. Most of postoperative PVR (77.2%) appeared in the first month after surgery. CONCLUSIONS: This study establishes the incidence of PVR, and its time of onset, but it was not effective to identify clinical risk factors with a high level of confidence.

Adolescent↗

Main pancreatic duct: morphlogy after acute biliary pancreatitis with magnetic resonance cholangiopancreatography after secretin stimulation.

OBJECTIVE: to assess whether a magnetic resonance cholangiopancreatography performed after an acute biliary pancreatitis leads to pancreatic morphological alterations and if secretin stimulation influences the visualization of the pancreatic tree. METHOD: forty patients with acute biliary pancreatitis, 25 female (62,5/) and 15 male (37,5/), 27 mild and 13 severe, were prospectively and consecutively studied. All patients had undergone cholecystectomy. No altered pancreatic functions were observed. Morphology of the pancreas and of the main pancreatic duct were assessed by magnetic resonance cholangiopancreatography five years after the episode of pancreatitis and a comparative study between patients and case controls was carried out. Secretin was given in 16 cases in whom the visualization of the duct was incomplete or absent. Ductal morphology before and after secretin stimulation was compared. RESULTS: significant differences were observed when the diameter and length of the main pancreatic duct were compared in patients and control cases and was completely visualized in 60% of the cases, and could be seen in all patients after secretin stimulation. The comparative statistical analysis of the length and diameter of the pancreatic duct before and after the secretin stimulation showed significant differences. CONCLUSION: acute biliary pancreatitis leads to morphological alterations, regarded as scar lesions which do not become chronic. Secretin stimulation improves the visualization of the main pancreatic duct.

Acute Disease↗

Intracisternal urocortin inhibits vagally stimulated gastric motility in rats: role of CRF(2).

1. Corticotropin-releasing factor (CRF) acts in the brain to inhibit thyrotropin-releasing hormone (TRH) analogue, RX-77368-induced vagal stimulation of gastric motility. We investigated CRF receptor-mediated actions of rat urocortin (rUcn) injected intracisternally (ic) on gastric motor function. 2. Urethane-anaesthetized rats with strain gauges on the gastric corpus were injected i.c. with rUcn and 20 min later, with i.c. RX-77368. CRF antagonists were injected i.c. 10 min before rUcn. 3. RX-77368 (1.5, 3, 10, 30 and 100 ng, i.c.) dose-dependently increased corpus contractions, expressed as total area under the curve (AUC, mV min(-1)) to 2.6+/-2.5, 6.1+/-5.9, 9.8+/-2.6, 69.7+/-21.7 and 74.9+/-28.7 respectively vs 0.2+/-0.1 after i.c. saline. Ucn (1, 3 or 10 microg) inhibited RX-77368 (30 ng)-induced increase in total AUC by 28, 62 and 93% respectively vs i.c. saline+RX-77368. 4. The CRF(1)/CRF(2) antagonist, astressin-B (60 microg, i.c.) completely blocked i.c. rUcn (3 microg, i.c.)-induced inhibition of gastric motility stimulated by RX-77368 (30 ng). 5. The selective CRF(2) antagonist, astressin(2)-B (30, 60 or 100 microg, i.c. ) dose-dependently prevented i.c. rUCn action while the CRF(1) antagonist, NBI-27914 did not. 6. In conscious rats, rUcn (0.6 or 1 microg, i.c.) inhibited gastric emptying of an ingested chow meal by 61 and 92% respectively. rUcn action was antagonized by astressin(2)-B. 7. These data show that i.c. rUcn acts through CRF(2) receptors to inhibit central vagal gastric contractile response and postoprandial emptying.

Animals↗

Entrance in mitosis of adult cardiomyocytes in ischemic pig hearts after plasmid-mediated rhVEGF165 gene transfer.

Replacement of the cell loss occurring after acute myocardial infarction has been proposed as a potential treatment to prevent heart remodeling and failure. On account that cardiomyocytes express VEGF receptors and that VEGF triggers mitogen-activated protein kinases, we investigated if VEGF gene transfer may induce cardiomyocyte replication. In a pig model of chronic myocardial ischemia achieved by Ameroid occlusion of the left circumflex coronary artery, we observed that direct intramyocardial injection of a plasmid encoding human VEGF(165) induced a several-fold increase in cardiomyocyte mitotic index and in the number of cardiomyocyte nuclei per unit volume as compared with pigs receiving plasmid devoid of gene. Despite images of conventional cytokinesis were not observed, the fact that caryokinesis is an obligatory step for cell division suggests that our finding may contribute to the issue of heart regeneration and may potentially widen the therapeutic spectrum of VEGF gene transfer.

Animals↗

Role of individual and contextual effects in injury mortality: new evidence from small area analysis.

OBJECTIVE: To analyse the role of individual and contextual variables in injury mortality inequalities from a small area analysis perspective, looking at the data for the city of Barcelona (Spain) for 1992-98. SETTING: Barcelona (Spain). METHODS: All injury deaths in residents older than 19, which occurred in the period 1992-98 were included (n=4393). Age and sex specific mortality rates were calculated for each educational level and each cause of death (traffic injuries, falls, drug overdose, suicide, other injuries). The contextual variables included were the proportion of men unemployed, and the proportion of men in jail, in each neighbourhood. Multilevel Poisson regression models were fitted using data grouped by age, educational level, and neighbourhood for each sex. RESULTS: Death rates were higher in males, at the extremes of the age distribution (under 44 and over 74 years), and for lower educational levels. The results of the Poisson multilevel models indicate that inequalities by educational level follow a gradient, with higher risks for the population with no schooling, after having adjusted for the contextual variables of the neighbourhood. Such inequalities were more important in the youngest age group (20-34 years), as relative risk of 5.41 (95% confidence interval (CI) 3.9 to 7.4) for all injury causes in males and 4.38 (95% CI 2.3 to 8.4) in females. The highest relative risks were found for drug overdose. There was a contextual neighbourhood effect (the higher the deprivation, the higher the mortality) after having taken into account individual variables. CONCLUSION: The findings underscore the need to implement injury prevention strategies not only at the individual level taking into account socioeconomic position, but also at the neighbourhood level.

Adult↗

Proton magnetic resonance spectroscopy in dementia with Lewy bodies.

Proton magnetic resonance spectroscopy ((1)H-MRS) provides a non-invasive, in vivo insight into the brain metabolism, and has been successfully used in several neurological conditions. Our objective was to characterise the cerebral metabolic changes in dementia with Lewy bodies (DLB) patients using (1)H-MRS. Single Voxel (1)H-MRS was performed in 12 DLB patients with mild to moderate symptoms and 11 age-matched healthy controls. Volumes of interest (VOI) were selected, including white matter (WM) in the centrum semiovale and grey matter (GM) in the parasagittal parietal cortex. Main metabolic peaks corresponding to N-acetylaspartate (NAA), glutamate/glutamine (Glx), choline-containing compounds (Cho), myo-inositol (Ins), and creatine plus phosphocreatine (Cr) were identified. These areas were measured and referred to that of the water. Metabolic ratios among the different peak areas were also calculated. In comparison with the control group, DLB patients showed significantly lower mean NAA/Cr, Glx1/Cr and Cho/Cr ratios in the WM, while their Ins/Cr and Ins/NAA ratios did not differ from those of the control group. In the GM, no significant differences were found between both groups. Correlations between age at onset, disease duration, Mini-Mental State Examination, the motor section of the Unified Parkinson's Disease Rating Scale, Hoehn and Yahr staging and metabolic ratios, both for WM and GM, were not significant in DLB patients. Our spectroscopy data show WM involvement, along with GM preservation, in DLB patients with early or intermediate stages. Hence, (1)H-MRS may provide adjunctive information in the ante-mortem diagnosis of DLB.

Aged↗

Arteriovenous haemangioma of the pterygoid process. Report of a case.

Arteriovenous haemangioma is a benign tumor which in ear, nose and throat practice is generally found in the soft tissues of the oral cavity. Bone involvement is very uncommon. These lesions typically manifest themselves in infancy, with a tendency towards spontaneous resolution. The management options comprise simple observation, embolization or surgical removal--depending on the location of the tumour and its symptoms. A correct diagnosis is essential to ensure the adoption of adequate measures during surgery. The present case describes an exceptional location of arteriovenous hemangioma of the pterygoid process, and discusses the associated diagnostic and treatment problems.

Adult↗

Role of CRF receptor 1 in central CRF-induced stimulation of colonic propulsion in rats.

The CRF receptor subtype mediating the colonic and gastric motor responses to central CRF was investigated in conscious rats. CRF (0.6 microg/rat) injected intracerebroventicularly (i.c.v.) or 1 h water avoidance stress stimulated defecation (pellet/60 min: 4.1+/-1.0 and 8.7+/-0.7 respectively vs. 0.3+/-0.3 in i.c.v. vehicle/no stress). The CRF receptor 1 (CRF-R1) antagonist, NBI-27914 (50-100 microg/rat) injected i.c.v., abolished the colonic response to i.c.v. CRF and dose-dependently reduced that induced by water avoidance stress. NBI-27914 (100 microg/rat) injected peripherally did not influence the defecatory response to stress. The peptide CRF-R1/R2 antagonist, astressin (10 microg/rat, i.c.v.) inhibited the colonic motor response to i.c.v. CRF and stress similarly as NBI-27914 injected i.c.v. at 100 microg/rat. Intracisternal (i.c.) injection of astressin (10 microg/rat) also completely prevented CRF (0.6 g, i.c.)-induced delayed gastric emptying while i.c. NBI-27914 (50 or 100 microg) had no effect. These results indicate a differential role of central CRF receptor subtypes in the colonic stimulatory and gastric inhibitory motor responses to central CRF and that the CRF component of stress-related activation of colonic expulsion is primarily mediated by CRF-R1.

Animals↗

Central TRH receptor 1 antisense blocks cold-induced gastric emptying but not brain c-Fos induction.

We studied whether TRH receptor 1 (TRH-R1) antisense oligodeoxynucleotides injected intracisternally, impaired acute cold-induced c-Fos expression in the brain and vagally mediated stimulation of gastric emptying in conscious rats. Cold exposure (4-6 degrees C, 90 min) increased gastric emptying and the number of c-Fos positive cells in the paraventricular nucleus of the hypothalamus, supraoptic nucleus, raphe pallidus, dorsal motor nucleus of the vagus, nucleus of the solitary tract and area postrema compared with rats at room temperature. TRH-R1 antisense abolished cold-induced stimulation of gastric transit but not c-Fos expression in the brain. TRH-R1 mismatch did not alter the gastric response to cold. These data indicate that central activation of TRH-R1 mediates cold-induced stimulation of gastric emptying but does not influence the induction of c-Fos expression in the brain.

Animals↗

Peripheral urocortin inhibits gastric emptying and food intake in mice: differential role of CRF receptor 2.

Intraperitoneal urocortin inhibits gastric emptying and food intake in mice. We investigated corticotropin-releasing factor receptor (CRF-R) subtypes involved in intraperitoneal urocortin actions using selective CRF-R antagonists. Gastric emptying was measured 2 h after a chow meal, and food intake was measured hourly after an 18-h fast in mice. Urocortin (3 microg/kg ip) inhibited gastric emptying by 88%. The CRF-R1/CRF-R2 antagonist astressin B (30 microg/kg ip) and the selective CRF-R2 antagonist antisauvagine-30 (100 microg/kg ip) completely antagonized urocortin action, whereas the selective CRF-R1 antagonist CP-154,526 (10 mg/kg ip) had no effect. Urocortin (1-10 microg/kg ip) dose dependently decreased the 2-h cumulative food intake by 30-62%. Urocortin (3 microg/kg)-induced hypophagia was completely antagonized by astressin B (30 microg/kg ip) and partially (35 and 31%) by antisauvagine-30 (100 or 200 microg/kg ip). The CRF-R1 antagonists CP-154,526 or DMP904 (10 mg/kg ip) had no effect. Capsaicin did not alter urocortin-inhibitory actions while blocking the satiety effect of intraperitoneal CCK. These data indicate that intraperitoneal urocortin-induced decrease in feeding is only partly mediated by CRF-R2, whereas urocortin action to delay gastric emptying of a meal involves primarily CRF-R2.

Animals↗

Magnetic resonance imaging of the pharynx in OSA patients and healthy subjects.

Obstructive sleep apnoea (OSA) occurs because of recurrent narrowing and occlusion of the velopharynx (VP) during sleep. The specific cause of OSA is unknown. Cephalometric radiography, fibreoptic nasopharyngoscopy, acoustic reflection techniques, and computerized tomography have limitations (dynamic and tridimensional evaluation) in the mechanism of occlusion investigation. Static and dynamic examination of the soft tissue structures surrounding the upper airway during the respiratory cycle in wakefulness and sleep, can lead to a better understanding of the process. Ultrafast magnetic resonance imaging (one image per 0.8 s) was used to study the upper airway and surrounding soft tissue in 17 patients with OSA during wakefulness and sleep, and in eight healthy subjects whilst awake. The major findings of this investigation in the 25 subjects were as follows: 1) the VP was smaller in apnoeic patients, only during part of the respiratory cycle; 2) the variation in VP area during the respiratory cycle was greater in apnoeic patients than in controls, particularly during sleep, suggesting an increased compliance of the VP in these patients; 3) VP narrowing was similar in the lateral and anterior-posterior dimensions, both in controls and apnoeic patients while awake; apnoeic patients during sleep have a more circular VP upon reaching the minimum area; 4) there was an inverse relationship between dimensions of the lateral pharyngeal walls and airway area, probably indicating that lateral walls are passively compressed or stretched as a result of changes in the airway calibre; and 5) soft palate and parapharyngeal fatpads were larger in apnoeic patients, although their role in the genesis of OSA is uncertain. It was concluded that changes in the velopharynx area and diameter during the respiratory cycle are greater in apnoeic patients than in normal subjects, particularly during sleep. This suggests that apnoeic patients have a more collapsible velopharynx, this being the main mechanism of obstruction.

Adult↗

Synergistic interaction between CCK and leptin to regulate food intake.

Leptin administered (either intracerebroventricularly, icv, or intraperitoneally, ip) acts in synergy with CCK to suppress food intake and body weight in lean mice or rats. The potentiating effect induced by the co-injection of ip CCK and leptin to inhibit food consumption in mice is mediated by the CCK-A receptor and capsaicin sensitive afferents. In vitro, studies in rats showed that a subset of gastric vagal afferent fibers responded to leptin injected directly into the gastric artery only after a prior intra-arterial CCK injection. Moreover, the tonic activity of gastric-related neurons in the nucleus tractus solitarius (NTS) increased when leptin was delivered into the gastric chamber of an in vitro stomach-brainstem preparation. CCK co-injected with leptin potentiated Fos expression selectively in the area postrema, NTS and paraventricular nucleus of the hypothalamus (PVN), which points to the PVN as part of the afferent and efferent limbs of the circuitry involved in the synergistic interaction between leptin and CCK. The dampening of CCK or leptin inhibitory action on ingestive behavior when either factor is not present or their receptors are non functional supports the notion that such leptin-CCK interaction may have a physiological relevance. These observations provide a mean through which leptin and CCK integrate short- and mid-term meal-related input signals into long-term control of energy balance.

Animals↗

Determination of the pKa values of beta-blockers by automated potentiometric titrations.

The acid-base equilibrium constants of the beta-blockers atenolol, oxprenolol, timolol and labetalol were determined by automated potentiometric titrations. The pKa values were obtained in water-rich or water methanol medium (20% MeOH) to obviate the solubility problems associated with the compounds. The initial estimates of pKa values were obtained from Gran's method and then, were refined by the NYTIT and ZETA versions of the LETAGROP computer program. The resultant values were 9.4 (I = 0.1 M KCl, 20% methanol) for atenolol, 9.6 (I = 0.1 M KCl) for oxprenolol, 9.4 (I = 0.1 M KCl, 20% methanol) for timolol and 7.4 and 9.4 (I = 0.1 M KCl) for labetalol. The potentiometric method was found to be accurate and easily applicable. The operational criteria for applying the methodology are indicated.

Adrenergic beta-Antagonists↗

Ammonium, bicarbonate and calcium effects on tomato plants grown under saline conditions.

Tomato plants (70 days old) were grown in hydroponic culture into a greenhouse, where supply of inorganic carbon, ammonium and calcium to saline nutrient solution, was investigated in order to reduce the negative effect of salinity. After 70 days, an ameliorating effect upon the decrease in growth observed under salinity was only observed with the treatments NaCl+Ca(2+) and NaCl+HCO(3)(-)+NH(4)(+)+Ca(2+). A large reduction of hydraulic conductance (L(0)) and stomatal conductance (G(s)) was observed with all treatments, compared with the control. However, the reductions were less when NaCl and Ca(2+) were added together. Organic acids (mainly malic acid) in the xylem were decreased with all treatments except with NaCl+NH(4)(+) and with all single treatments added together (NaCl+HCO(3)(-)+NH(4)(+)+Ca(2+)). Amino acid concentrations in the xylem (mainly asparagine and glutamine) decreased when plants were treated with NaCl and NaCl+Ca(2+), but there was a large increase in the plants treated with NaCl+NH(4)(+) or with all treatments together. As HCO(3)(-) is an important source of carbon for NH(4)(+) assimilation, the increase in the concentration of amino acids and organic acids caused by the treatments that contained NH(4)(+), support the idea that fixation of dissolved inorganic carbon was occurring and that the products were transported via the xylem to the shoot. The ameliorating effect of Ca(2+) on root hydraulic conductivity plus the increase of NH(4)(+) incorporation into the amino acid synthesis pathway possibly due to dissolved inorganic carbon fixation, could reduce the negative effect of salinity on tomato plants.

Journal Article↗

High-performance liquid chromatography with amperometric detection applied to the screening of 1,4-dihydropyridines in human plasma.

A high-performance liquid chromatographic method with electrochemical detection has been developed for the determination of six 1,4-dihydropyridines: nifedipine, nimodipine, nisoldipine, nicardipine, felodipine and lacidipine. The chromatographic separation was performed using a Supelcosil LC-ABZ+Plus C18 column. A mobile phase of methanol-water (70:30), containing 2 mM CH3COOH-CH3COONa at a flow-rate of 1 ml/min and a pH of 5.0, was used. The temperature was optimized at 30+/-0.2 degrees C. The amperometric detector, equipped with a glassy carbon electrode, was operated at 1000 mV versus Ag/AgCl in the direct current mode. The method was applied to the determination of these compounds at ng/ml concentrations, obtaining intra-day reproducibilities of lower than 5.0% in terms of relative standard deviations and detection limits ranging from 16 to 44 ng/ml. The method was applied to the screening of 1,4-dihydropyridines in spiked plasma samples, with a total elution time of lower than 18 min, obtaining the best recoveries for nimodipine and felodipine (91 and 88%, respectively). These recoveries together with the low detection limits achieved allow its application to the analysis of these drugs in human plasma.

Calcium Channel Blockers↗

Fos induction in selective hypothalamic neuroendocrine and medullary nuclei by intravenous injection of urocortin and corticotropin-releasing factor in rats.

CRF and urocortin, administrated systemically, exert peripheral biological actions which may be mediated by brain pathways. We identified brain neuronal activation induced by intravenous (i.v.) injection of CRF and urocortin in conscious rats by monitoring Fos expression 60 min later. Both peptides (850 pmol/kg, i.v.) increased the number of Fos immunoreactive cells in the paraventricular nucleus of the hypothalamus, supraoptic nucleus, central amygdala, nucleus tractus solitarius and area postrema compared with vehicle injection. Urocortin induced a 4-fold increase in the number of Fos-positive cells in the supraoptic nucleus and a 3.4-fold increase in the lateral magnocellular part of the paraventricular nucleus compared with CRF. Urocortin also elicited Fos expression in the accessory hypothalamic neurosecretory nuclei, ependyma lining the ventricles and choroid plexus which was not observed after CRF. The intensity and pattern of the Fos response were dose-related (85, 255 and 850 pmol/kg, i.v.) and urocortin was more potent than CRF. Neither CRF nor urocortin induced Fos expression in the lateral septal nucleus, Edinger-Westphal nucleus, dorsal raphe nucleus, locus coeruleus, or hypoglossal nucleus. These results show that urocortin, and less potently CRF, injected into the circulation at picomolar doses activate selective brain nuclei involved in the modulation of autonomic/endocrine function; in addition, urocortin induces a distinct activation of hypothalamic neuroendocrine neurons.

Amygdala↗