Biomedical subjects

Vicente Martínez

Publications and source records attributed to Vicente Martínez.

At least 19 recordsLinked to original sources

PubMed2006

Functional CRF receptors in BON cells stimulate serotonin release.

BON cells are human, pancreatic carcinoid-derived, endocrine-like cells that share functional similarities with intestinal enterochromaffin (EC) cells. We investigated the presence of corticotropin-releasing factor (CRF) receptors, their signalling pathways and the functional effects of their stimulation in BON cells (clone #7). Expression analysis showed that BON cells contain mRNA for the CRF receptor types 1 and 2 (CRF1/2), although CRF2 mRNA levels were 23-fold higher than those of CRF1 mRNA. The CRF1/2 ligand, rat/human (r/h)CRF (EC50 = 233 nM), and the selective CRF2 ligand, human urocortin 3 (Ucn 3) (EC50 = 48 nM), induced a dose-dependent increase in cAMP formation. Effects of r/hCRF were blocked by 44% with the selective CRF1 antagonist DMP-696, while the selective CRF2 antagonist antisauvagine-30 had only marginal effects. Both ligands (100 nM) stimulated the release of serotonin with similar efficacy (3-fold increase over basal). Effects of r/hCRF, but not Ucn 3, were blocked by pre-incubation with antisauvagine-30. These observations demonstrate that the EC cell-related BON cells express functional CRF2 receptors linked to the release of serotonin. This suggests that EC cells may be a target for CRF and/or Ucn 3 in the intestine during stress-related responses. Actions of CRF/Ucn 3 and EC cell-derived mediators, such as serotonin, might underlie several motor, secretory and/or sensory disorders of the gastrointestinal (GI) tract which may play a role in the pathophysiology of functional GI disorders, such as irritable bowel syndrome.

Cell Line, Tumor↗

PubMed2006

Proximal colon distension induces Fos expression in the brain and inhibits gastric emptying through capsaicin-sensitive pathways in conscious rats.

We assessed brain nuclei activated during noxious mechanical distension of the proximal colon in conscious rats, using Fos as a marker of neuronal activation, and functional reflex changes in gastric emptying associated to colon distension. The role of capsaicin-sensitive afferents in Fos and gastric responses to distension was also investigated. Compared with sham distension, isovolumetric phasic distension of the proximal colon (10 ml, 30 s on/off for 10 min) increased significantly Fos expression 1 h after distension in selective brain areas, most prominently, the paraventricular and supraoptic nuclei of the hypothalamus (13-fold and 80-fold, respectively), the locus coeruleus-Barrington's nucleus complex (2-fold), area postrema (7-fold) and the nucleus tractus solitarius (4-fold). Increased Fos expression was also observed in the cingulate cortex, posterior paraventricular nucleus of the thalamus, periaqueductal gray and ventrolateral medulla. Distension of the proximal colon significantly inhibited gastric emptying by 82% and 34%, as measured 30 and 60 min after the distension respectively, compared with control. Pretreatment with systemic capsaicin prevented both the brain increase in Fos expression and the inhibition of gastric emptying induced by the colon distension. These results show that visceral pain arising from the proximal colon activates a complex neuronal network that includes specific brain nuclei involved in the integration of autonomic, neuroendocrine and behavioral responses to pain and an inhibitory motor reflex in other gut areas (delayed gastric emptying). Capsaicin-sensitive afferent pathways are involved in mediating brain neuronal activation and functional changes associated with noxious visceral stimulation.

Analysis of Variance↗

PubMed2006

In a randomized controlled trial, cataract surgery in both eyes increased benefits compared to surgery in one eye only.

BACKGROUND AND OBJECTIVE: Despite recommendation of surgery in both eyes in patients with bilateral cataract, there is little evidence about the benefits of second-eye surgery. The objective of this study was to compare the benefits of cataract surgery in both eyes with those of surgery in one eye only. STUDY DESIGN AND SETTING: Two-arm randomized controlled trial involving 296 patients with bilateral cataracts of two public teaching hospitals. Patients were randomly assigned to receive surgery in one eye only (control group) or surgery in both eyes, one eye at a time (intervention group). The main outcome measures were binocular visual acuity, binocular contrast sensitivity, stereopsis, and patient-reported visual disability (VF-14), measured 4-6 months postoperatively. RESULTS: A total of 135 (91.2%) and 139 (93.9%) patients completed the trial in the control and intervention groups, respectively. Postoperatively, intervention group presented a better visual acuity (difference of 0.07; 95% CI = 0.03, 0.12), stereopsis (0.62 log sec arc; 95% CI = 0.45, 0.79), and VF-14 (8.2 points; 95% CI = 4.4, 12.4). No significant differences were found for contrast sensitivity. CONCLUSIONS: Bilateral cataract patients should have surgery in both eyes. Including stereopsis and patient-reported visual disability in the assessment of cataract patients, especially after first-eye surgery, will improve the evaluation of effectiveness.

Aged↗

PubMed2006

[Magnetic resonance imaging evidence of the effectiveness of combination chelation therapy in iron overload cardiomyopathy].

Heart failure secondary to iron overload is the main cause of death in patients with beta-thalassemia major. Combination therapy with deferoxamine and deferiprone has been shown to be more effective than either drug used alone in patients with beta-thalassemia major and symptomatic cardiomyopathy. Although monitoring the response to chelation therapy is usually carried out by indirect measurement of the serum ferritin level or by direct determination of tissue iron content in biopsy specimens, magnetic resonance imaging (MRI) seems to be useful for noninvasive qualitative and quantitative assessment of iron deposition. We present a case in which the efficacy of double chelation therapy in a patient with beta-thalassemia major and heart failure was demonstrated by MRI.

Adult↗

PubMed2005

High-affinity K+ uptake in pepper plants.

High-affinity K+ uptake is an essential process for plant nutrition under K+-limiting conditions. The results presented here demonstrate that pepper (Capsicum annuum) plants grown in the absence of NH4+ and starved of K+ show an NH4+-sensitive high-affinity K+ uptake that allows plant roots to deplete external K+ to values below 1 microM. When plants are grown in the presence of NH4+, high-affinity K+ uptake is not inhibited by NH4+. Although NH4+-grown plants deplete external K+ below 1 microM in the absence of NH4+, when 1 mM NH4+ is present they do not deplete external K+ below 10 microM. A K+ transporter of the HAK family, CaHAK1, is very likely mediating the NH4+-sensitive component of the high-affinity K+ uptake in pepper roots. CaHAK1 is strongly induced in the roots that show the NH4+-sensitive high-affinity K+ uptake and its induction is reduced in K+-starved plants grown in the presence of NH4+. The NH4+-insensitive K+ uptake may be mediated by an AKT1-like K+ channel.

Biological Transport, Active↗

PubMed2005

Acute biliary pancreatitis: does the pancreas change morphologically in the long term?

The objective of the study was to assess by means of magnetic resonance cholangiopancreatography whether acute biliary pancreatitis leads to alterations in pancreatic morphology and the main pancreatic duct; to establish whether such alterations are related to the severity of the acute episode and if they are to be considered as sequelae of the illness or on the contrary the findings constitute diagnostic morphological criteria of chronic pancreatitis. Forty patients with acute biliary pancreatitis were prospectively and consecutively studied, 15 female (37.5%) and 25 male (62.5%). During the acute phase the severity was assessed according to the Atlanta criteria. During subsequent follow-up,we assessed the morphology of the gland and the main pancreatic duct with magnetic resonance cholangiopancreatography 5 years after the episode of pancreatitis, and compared the findings with the findings from a control group. We administered secretin in 16 of the study group cases when visualization of the duct was incomplete or absent. The statistical study of diameter and length showed significant differences in the main pancreatic duct of the case and control groups. No relationship was found between the severity of the illness and morphological alterations of the pancreas after pancreatitis. The statistical analysis, which compared the diameter and the length of the main pancreatic duct before and after the injection of secretin in the study group showed significant differences. We conclude that after acute biliary pancreatitis, in the long term, scarring lesions are detected, which are considered to be sequelae of the acute episode, unrelated to its severity. Secretin stimulation improved visualization of the main pancreatic duct in the magnetic resonance cholangiopancreatography.

Acute Disease↗

PubMed2005

Molecular characterization and genetic variation of the VP7 gene of human rotaviruses isolated in Paraguay.

Rotavirus is the main cause of acute diarrhea in infants and young children worldwide. In Paraguay, acute diarrhea ranks fourth among the causes of mortality in children under 4 years of age. Rotavirus was detected in 93 out of 410 patients admitted to three main hospitals in Asunción, Paraguay from August 1998 to August 2000. Samples from 64 patients were analyzed by RT-PCR for G and P typing. G4P[8] (46.9%; 30/64) was the most common strain detected, followed by G9P[8] (17.2%; 11/64) and G1P[8] (10,9%; 7/64). Since G4 was predominant during the epidemiological peaks of 1998 and 1999, four samples were sequenced and all grouped into sublineage Ic. This sublineage was reported for the first time in 1998 in Argentina, southern border of Paraguay, and it was shown to be responsible for the increased prevalence of G4 during the epidemiological season of 1998 in that country. In addition, Paraguayan G1 strains grouped in different lineages (I and II). However, G9 was predominant during the rotavirus epidemiological peak of 2000, and phylogenetic analysis of five samples grouped into a common emergent/reemergent lineage that circulates worldwide. Since vaccination could reduce the severity and the number of cases of rotavirus disease, this study suggests that a vaccine containing recently isolated variants of the most prevalent types (G1-G4) together with the emerging G9 type, might be sufficient to elicit a protective immune response against the rotavirus types circulating currently in Paraguay.

Antigens, Viral↗

PubMed2004

Role of somatostatin receptors on gastric acid secretion in wild-type and somatostatin receptor type 2 knockout mice.

Somatostatin, probably acting through somatostatin type 2 receptors (SSTR2), is the main inhibitor of gastric acid secretion. We characterized gastric acid secretion in SSTR2 knockout mice, and used preferential somatostatin receptor agonists to assess the relative role of SSTR1, 2, 3, 4, and 5 on gastric acid secretion. Basal gastric acid secretion and the secretory response to a meal were similar in conscious wild-type and knockout mice. However, under urethane anesthesia, which releases endogenous somatostatin, SSTR2 knockout mice had a basal secretion 11-15-fold higher than wild-type animals (micromol/10 min:1.40+/-0.09 vs. 0.10+/-0.01, p<0.05). Gastrin immunoneutralization or H(2) receptors blockade (cimetidine), but not cholinergic blockade (atropine), reduced the high basal secretion in SSTR2 knockout mice. In SSTR2 knockout mice, gastrin and histamine stimulated acid secretion with similar efficacy, while in wild-type mice histamine was more effective than gastrin. SSTR2 knockout mice showed also a hypersecretory response to pylorus ligation compared with wild-type animals. In wild-type mice, somatostatin-14, SMS 201-995, and the SSTR2-preferential agonist, DC 32-87, inhibited gastrin-stimulated acid secretion with an order of potency SMS 201-995>DC 32-87>somatostatin-14. Preferential agonists for the SSTR1, 3, 4, and 5 were devoid of any effect. None of the compounds tested affected the high basal secretion observed under urethane anesthesia in SSTR2 knockout mice. These results show that gastric antisecretory effects of peripheral somatostatin are mediated solely through SSTR2. In the absence of functional SSTR2 other somatostatin receptors do not compensate for the lack somatostatin-SSTR2-mediated inhibition. Basal acid secretion and the response to a meal are normal in conscious SSTR2 knockout mice, suggesting the presence of somatostatin-independent mechanisms that compensate for the lack of somatostatin-SSTR2-mediated inhibitory responses.

Animals↗

PubMed2004

Peripheral PACAP inhibits gastric acid secretion through somatostatin release in mice.

1. Studies in rats suggest that PACAP modulates gastric acid secretion through the release of both histamine and somatostatin. 2. We characterized the effects of exogenous PACAP on gastric acid secretion in urethane-anesthetized mice implanted with a gastric cannula and in conscious 2-h pylorus ligated mice, and determined the involvement of somatostatin and somatostatin receptor type 2 (SSTR2) by using somatostatin immunoneutralization, the SSTR2 antagonist, PRL-2903, and SSTR2 knockout mice. 3. Urethane-anesthetized wild-type mice had low basal acid secretion (0.10+/-0.01 micromol (10 min)(-1)) compared with SSTR2 knockout mice (0.93+/-0.07 micromol (10 min)(-1)). Somatostatin antibody and PRL-2903 increased basal secretion in wild-type mice but not in SSTR2 knockout animals. 4. In wild-type urethane-anesthetized mice, PACAP-38 (3-270 microg kg(-1) h(-1)) did not affect the low basal acid secretion, but inhibited the acid response to pentagastrin, histamine, and bethanechol. 5. In wild-type urethane-anesthetized mice pretreated with somatostatin antibody or PRL-2903 and in SSTR2 knockout mice, peripheral infusion of PACAP-38 or somatostatin-14 did not inhibit the increased basal gastric acid secretion. 6. In conscious wild-type mice, but not in SSTR2 knockout mice, PACAP-38 inhibited gastric acid secretion induced by 2-h pylorus ligation. The antisecretory effect of PACAP-38 was prevented by immunoneutralization of somatostatin. 7. These results indicate that, in mice, peripheral PACAP inhibits gastric acid secretion through the release of somatostatin and the activation of SSTR2 receptors. There is no evidence for stimulatory effects of PACAP on acid secretion in mice.

Animals↗

PubMed2004

Central CRF, urocortins and stress increase colonic transit via CRF1 receptors while activation of CRF2 receptors delays gastric transit in mice.

Recently characterized selective agonists and developed antagonists for the corticotropin releasing factor (CRF) receptors are new tools to investigate stress-related functional changes. The influence of mammalian CRF and related peptides injected intracerebroventricularly (i.c.v.) on gastric and colonic motility, and the CRF receptor subtypes involved and their role in colonic response to stress were studied in conscious mice. The CRF(1)/CRF(2) agonists rat urocortin 1 (rUcn 1) and rat/human CRF (r/h CRF), the preferential CRF(1) agonist ovine CRF (oCRF), and the CRF(2) agonist mouse (m) Ucn 2, injected i.c.v. inhibited gastric emptying and stimulated distal colonic motor function (bead transit and defecation) while oCRF(9-33)OH (devoid of CRF receptor affinity) showed neither effects. mUcn 2 injected peripherally had no colonic effect. The selective CRF(2) antagonist astressin(2)-B (i.c.v.), at a 20 : 1 antagonist: agonist ratio, blocked i.c.v. r/hCRF and rUcn 1 induced inhibition of gastric transit and reduced that of mUcn 2, while the CRF(1) antagonist NBI-35965 had no effect. By contrast, the colonic motor stimulation induced by i.c.v. r/hCRF and rUcn 1 and 1h restraint stress were antagonized only by NBI-35965 while stimulation induced by mUcn 2 was equally blocked by both antagonists. None of the CRF antagonists injected i.c.v. alone influenced gut transit. These data establish in mice that brain CRF(1) receptors mediate the stimulation of colonic transit induced by central CRF, urocortins (1 and 2) and restraint stress, while CRF(2) receptors mediate the inhibitory actions of these peptides on gastric transit.

Animals↗

PubMed2004

Cloning and functional characterization of the high-affinity K+ transporter HAK1 of pepper.

High-affinity K+ uptake in plants plays a crucial role in K+ nutrition and different systems have been postulated to contribute to the high-affinity K+ uptake. The results presented here with pepper (Capsicum annum) demonstrate that a HAK1-type transporter greatly contributes to the high-affinity K+ uptake observed in roots. Pepper plants starved of K+ for 3 d showed high-affinity K+ uptake (Km of 6 microM K+) that was very sensitive to NH and their roots expressed a high-affinity K+ transporter, CaHAK1, which clusters in group I of the KT/HAK/KUP family of transporters. When expressed in yeast ( Saccharomyces cerevisiae ), CaHAK1 mediated high-affinity K+ and Rb+ uptake with Km values of 3.3 and 1.9 microM, respectively. Rb+ uptake was competitively inhibited by micromolar concentrations of NH and Cs+, and by millimolar concentrations of Na+.

Blotting, Northern↗

PubMed2004

Noninvasive assessment of gastric emptying by near-infrared fluorescence reflectance imaging in mice: pharmacological validation with tegaserod, cisapride, and clonidine.

Noninvasive near-infrared fluorescence reflectance imaging (FRI) is an in vivo technique to assess physiological and molecular processes in the intact organism. Here we describe a method to assess gastric emptying in mice. TentaGel beads with covalently bound cyanine dye (Cy5.5) conjugates as fluorescent probe were administered by oral gavage. The amount of intragastric beads/label was derived from the fluorescence signal intensity measured in a region of interest corresponding to the mouse stomach. The FRI signal intensity decreased as a function of time reflecting gastric emptying. In control mice, the gastric half-emptying time was in agreement with literature data. Pharmacological modulation of gastric motility allowed the evaluation of the sensitivity of the FRI-based method. Gastric emptying was either stimulated or inhibited by treatment with the 5-HT(4) receptor agonists tegaserod (Zelnorm) and cisapride or the alpha(2)-receptor agonist clonidine, respectively. Tegaserod and cisapride dose-dependently accelerated gastric emptying. In contrast, clonidine dose-dependently delayed gastric emptying. In conclusion, FRI using fluorescently labeled beads allows the reliable determination of gastric emptying as well as the assessment of pharmacological interventions. The technique thus offers the potential to characterize molecular targets and pathways involved in physiological regulation and pharmacological modulation of gastric emptying.

Adrenergic alpha-Agonists↗

PubMed2003

Somatostatin receptor type 2 mediates bombesin-induced inhibition of gastric acid secretion in mice.

Studies in isolated mouse stomach showed that bombesin releases somatostatin. We characterized the effects of exogenous bombesin on gastric acid secretion in mice and determined the involvement of somatostatin and somatostatin receptor type 2 (SSTR2) by using somatostatin immunoneutralization, the SSTR2 antagonist, PRL-2903, and SSTR2 knockout mice. Gastric acid secretion was monitored under basal and pentagastrin-, histamine- or bethanechol-stimulated conditions in urethane-anaesthetized mice. Bombesin (10-40 micro g kg-1 h-1) and somatostatin-14 (20 micro g kg-1 h-1) were infused I.V. 10 and 30 min after PRL-2903 or somatostatin antibody pretreatment, respectively. Urethane-anaesthetized wild-type mice had low basal acid secretion (0.12 +/- 0.01 micro mol (10 min)-1) compared with SSTR2 knockout mice (1.43 +/- 0.10 micro mol (10 min)-1). Somatostatin antibody and PRL-2903 increased basal secretion in wild-type mice but not in SSTR2 knockout animals. In wild-type mice, bombesin inhibited secretagogue-stimulated acid secretion in a dose-dependent manner, and somatostatin-14 inhibited pentagastrin-stimulated secretion. In wild-type mice pretreated with somatostatin antibody or PRL-2903 and in SSTR2 knockout mice, bombesin and somatostatin-14 I.V. infusion did not alter the increased gastric acid secretion. These results indicate that, in mice, bombesin inhibits gastric acid secretion through the release of somatostatin and the activation of SSTR2. These observations strengthen the important role of SSTR2 in mediating somatostatin inhibitory actions on gastric acid secretion.

Animals↗

PubMed2003

[Usefulness of magnetic resonance imaging in the assessment of endomyocardial disease].

Endomyocardial disease is a restrictive cardiomyopathy that includes Löffler endocarditis, which is characterized by hypereosinophilia, and endomyocardial fibrosis, which is not. Echocardiography enables cardiac function and anatomy to be assessed and the differential diagnosis of other causes of restrictive disease, but magnetic resonance imaging provides information about the tissue itself. Furthermore, paramagnetic contrast agents are useful in detecting myocardial abnormalities. We report three cases of endomyocardial disease and the typical findings of magnetic resonance imaging.

Adolescent↗

PubMed2003

Aquaporin functionality in relation to H+-ATPase activity in root cells of Capsicum annuum grown under salinity.

As water and nutrient uptake should be related in the response of plants to salinity, the aim of this paper is to establish whether or not aquaporin functionality is related to H+-ATPase activity in root cells of pepper (Capsicum annuum L.) plants. Thus, H+-ATPase activity was measured in plasma membrane vesicles isolated from roots and aquaporin functionality was measured using a cell pressure probe in intact roots. Salinity was applied as 60 mM NaCl or 60 mM KCl, to determine which ion (Na+, K+ or Cl-) is producing the effects. We also investigated whether the effects of both salts were ameliorated by Ca2+. Similar results were obtained for cell hydraulic conductivity, Lpc, and H+-ATPase activity, large reductions in the presence at NaCl or KCl and an ameliorative effect of Ca2+. However, fusicoccin (an activator of H+-ATPase) did not alter osmotic water permeability of protoplasts isolated from roots. Addition of Hg2+ inhibited both ATPase and aquaporins, but ATPase also contains Hg-binding sites. Therefore, the results indicate that H+-ATPase and aquaporin activities may not be related in pepper plants.

Journal Article↗

PubMed2003

Influence of saline stress on root hydraulic conductance and PIP expression in Arabidopsis.

Measurements of the root hydraulic conductance (L0) of roots of Arabidopsis thaliana were carried out and the results were compared with the expression of aquaporins present in the plasma membrane of A. thaliana. L0 of plants treated with different NaCl concentrations was progressively reduced as NaCl concentration was increased compared to control plants. Also, L0 of plants treated with 60 mmol/L NaCl for different lengths of time was measured. Variations during the light period were seen, but only for the controls. A good correlation between mRNA expression and L0 was observed in both experiments. Control plants and plants treated with 60 mmol/L NaCl were incubated with Hg and then with DTT. For these plants, L0 and cell-to-cell pathway contributions to root water transport were determined. These results revealed that in control plants most water movement occurs via the cell-to-cell pathway, thus implying aquaporin involvement. But, in NaCl-stressed plants, the Hg-sensitive cell-to-cell pathway could be inhibited already by the effect of NaCl on water channels. Therefore, short periods of NaCl application to Arabidopsis plants are characterised by decreases in the L0 of roots, and are related to down-regulation of the expression of the PIP aquaporins. This finding indicates that the well known effect of salinity on L0 could involve regulation of aquaporin expression.

Aquaporins↗

PubMed2003

Different blocking effects of HgCl2 and NaCl on aquaporins of pepper plants.

In this study we have compared the short-term effects of both NaCl and HgCl2 on aquaporins of Capsicum annuum L. plants, in order to determine whether or not they are similar. Stomatal conductance, turgor, root hydraulic conductance and water status were measured after 0.5, 2, 4 and 6 h of NaCl (60 mmol/L) or HgCl2 (50 micromol/L) treatment. When 60 mmol/L NaCl was added to the nutrient solution, a large decrease in stomatal conductance was observed after 2 h. However, when HgCl2 (50 micromol/L) was added, the decrease occurred after 4 h. The number of open stomata closed was always lower in plants treated with HgCl2 than in plants treated with NaCl. The water content of the Hg(2+)-treated plants was decreased, compared with controls and NaCl-treated. The root hydraulic conductance decreased after HgCl2 and NaCl treatment plants. Turgor of leaf epidermal cells was greatly reduced in plants treated with HgCl2, but remained constant in the NaCl treatment, compared with control plants. The fact that the stomatal conductance was reduced more rapidly after NaCl addition, followed by the stomatal closure, and that both water content and turgor did not differ from the control suggests that in NaCl-treated plants there must be a signal moving from root to shoot. Therefore, the control of plant homeostasis through a combined regulation of root and stomatal exchanges may be dependent on aquaporin regulation.

Aquaporins↗

PubMed2003

Tolerance of citrus rootstock seedlings to saline stress based on their ability to regulate ion uptake and transport.

Forty-five-day-old seedlings of sour orange (Citrus aurantium L.) and Citrus macrophylla Wester, the most commonly used rootstocks in lemon orchards, were grown in nutrient solutions containing 1 (control), 10, 20, 30 or 60 mM NaCl for 14 days. The effects of salinity on growth, uptake, transport and accumulation of Cl- and Na+ ions in leaves, stem and four root segments were studied. The 60 mM NaCl treatment reduced leaf dry mass more in C. macrophylla (40%) than in sour orange (20%), whereas it reduced root dry mass more in sour orange (36%) than in C. macrophylla (20%). In C. macrophylla, Cl- and Na+ uptake rates were high at the beginning of the saline treatments, but low at the end of the 14-day experiment. In contrast, sour orange showed high uptake rates at the beginning and end of the experiment. In response to increasing salinity, root and shoot concentrations of Cl- and Na+ increased in sour orange, but not in C. macrophylla. Different loading characteristics of Cl- and Na+ were observed between young and old segments of the root system. In general, old root segments reached quasi-steady-states later than young root segments. These results suggest that sour orange and C. macrophylla have different regulatory mechanisms for uptake and transport of Cl- and Na+.

Biomass↗