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P Vergara

Publications and source records attributed to P Vergara.

At least 19 recordsLinked to original sources
PubMed2006

Mast cell stabilizer ketotifen [4-(1-methyl-4-piperidylidene)-4h-benzo[4,5]cyclohepta[1,2-b]thiophen-10(9H)-one fumarate] prevents mucosal mast cell hyperplasia and intestinal dysmotility in experimental Trichinella spiralis inflammation in the rat.

Trichinella spiralis infection in rats induces hypermotility and an abnormal response to cholecystokinin (CCK) similar to motor disturbances observed in irritable bowel syndrome. Mast cell hyperplasia is also characteristic of this experimental model. The aim of our study was to correlate mast cell activity with the development of dysmotility and to demonstrate whether the mast cell stabilizer ketotifen [4-(1-methyl-4-piperidylidene)-4H-benzo[4,5]cyclohepta[1,2-b]thiophen-10(9H)-one fumarate] could prevent the development of intestine hypermotility. Sprague-Dawley rats were infected with T. spiralis and, 5 days after infection, treated with the mast-cell stabilizer ketotifen (10 mg/kg/day). Twelve days after infection, intestinal spontaneous motor activity and response to CCK were evaluated by means of strain-gauge transducers. Immunohistochemistry for rat mast cell protease II (RMCPII), cyclooxygenase (COX)-2, and inducible nitric-oxide synthase (iNOS) was performed in intestinal specimens. In addition, RMCPII and myeloperoxidase were determined in serum. Infected control rats showed hypermotility, mast cell hyperplasia, increased RMCPII levels, increased myeloperoxidase, and overexpression of COX-2 and iNOS. In contrast, ketotifen-treated rats showed spontaneous intestinal motility and CCK response similar to the noninfected control rats. Mast cell hyperplasia and RMCPII were reduced in ketotifen-treated rats. Inflammatory parameters were less modified by ketotifen, but those animals that received the longest ketotifen treatment showed a slight amelioration in these parameters. These results indicate that mast cells are implicated in the development of hypermotility. The treatment with ketotifen prevented hypermotility and mast cell hyperplasia and diminished mucosal mast cell activity.

Animals↗
PubMed2005

Cyclical upregulated iNOS and long-term downregulated nNOS are the bases for relapse and quiescent phases in a rat model of IBD.

We previously reported that indomethacin induces a chronic intestinal inflammation in the rat where the cyclical characteristic phases of Crohn's disease are manifested with a few days' interval and lasting for several months: active phase (high inflammation, hypomotility, bacterial translocation) and reactive phase (low inflammation, hypermotility, no bacterial translocation). In this study, we investigated the possible role of both constitutive and inducible isoforms of nitric oxide (NO) synthase (NOS) and cyclooxygenase (COX) in the cyclicity of active and reactive phases in rats with chronic intestinal inflammation. Rats selected at either active or reactive phases and from 2 to 60 days after indomethacin treatment were used. mRNA expression of both constitutive and inducible NOS and COX isoforms in each phase was evaluated by RT-PCR and cellular enzyme localization by immunohistochemistry. The effects of different COX and NOS inhibitors on the intestinal motor activity were tested. mRNA expression of COX-1 was not modified by inflammation, whereas mRNA expression of neuronal NOS was reduced in all indomethacin-treated rats. In contrast, NOS and COX inducible forms showed a cyclical oscillation. mRNA expression and protein of both iNOS and COX-2 increased only during active phases. The intestinal hypomotility associated with active phases was turned into hypermotility after the administration of selective iNOS inhibitors. Sustained downregulation of constitutive NOS caused hypermotility, possibly as a defense mechanism. However, this reaction was masked during the active phases due to the inhibitory effects of NO resulting from the increased levels of the inducible NOS isoform.

Animals↗
PubMed2005

Modification of dopaminergic markers expression in the striatum by neonatal exposure to glutamate during development.

Monosodium l-glutamate (MSG) was administered subcutaneously to male neonatal rats, and the effect on developmental profile of tyrosine hydroxylase (TH), D1, D2 receptors, and dopamine (DA) transporter expression in the striatum was examined using Western blot. In addition, TH-immunopositive neurons at substantia nigra (SN) were also examined. MSG treatment (4mg/g of body weight, administered on postnatal days 1, 3, 5, and 7) resulted in a reduction of D1 and D2 receptor expression from 30 days of age and persisted to adulthood (120 days of age), while DA transporter expression was significantly reduced from 14 days of age to adulthood. TH immunopositive neurons at SN showed a significant reduction, as well as TH expression on postnatal days 10, 30, 60, and 120 at striatum was reduced. No changes of TH were observed at 14 days of age. Results indicate that an over-stimulation of the glutamatergic system by neonatal exposure to a high glutamate concentration induces a partial loss in TH-positive neurons in the SN and an important reduction in dopaminergic markers expression in the striatum, suggesting that early excitotoxicity could contribute to developmental alterations in the nigrostriatal pathway, which may be associated with various disorders of the basal ganglia.

Aging↗
PubMed2005

[Respiratory muscle aids during an episode of aspiration in a patient with Duchenne muscular dystrophy].

We report the case of a Duchenne muscular dystrophy patient with good bulbar function but severely decreased forced vital capacity (9%) and spontaneous peak cough flow (PCF) (2.35 L/s). The patient needed continuous noninvasive ventilation (NIV) consisting of a volumetric ventilator with a nighttime nasal mask and a daytime mouthpiece. He also required application of manually assisted coughing techniques by insufflation with a resuscitation bag and chest thrust (manually assisted PCF after maximum insufflation capacity of 4.33 L/s). An episode of serious food aspiration was resolved by his main caregiver through NIV and manually assisted coughing. Bronchoscopy under sedation using NIV with a lip seal connection to his volumetric ventilator later revealed that no material remained. This case exemplifies the potential role of skilled respiratory management in some neuromuscular diseases.

Adult↗
PubMed2005

Hypersensitivity to ovalbumin induces chronic intestinal dysmotility and increases the number of intestinal mast cells.

Undiagnosed food allergies have been proposed as possible causes of promoting and perpetuating irritable bowel syndrome . Our aim was to find out if sensitization could induce chronic functional motor disturbances in the intestine and the mechanisms implicated. Rats were sensitized to ovalbumin (OVA) following three hypersensitivity induction protocols, two parenteral and one oral. Rat mast cell protease II (RMCP II) release in response to OVA challenge and immunoglobulin E (IgE) concentration were measured in serum. At least 1 week after challenge, small intestinal motility was evaluated using strain gauges. Intestinal tissue samples from orally sensitized rats were checked for in vitro stimulation with OVA. Mucosal mast cells were counted from duodenum sections. All sensitized rats showed intestinal hypermotility. Only rats sensitized by parenteral procedure showed an increase in RMCP II after OVA challenge in serum. IgEs increased only in the Bordetella pertussis sensitized group. Small intestine sections from orally sensitized rats released more RMCP II than sections from control rats. All sensitized rats showed an increase in the number of mucosal mast cells in duodenum. In conclusion, hypersensitivity to food proteins induces chronic motor alteration that persists long after antigen challenge and an excited/activated state of sensitized mucosal mast cells.

Animals↗
PubMed2003

Non-invasive management of an acute chest infection for a patient with ALS.

We describe a man diagnosed with non-bulbar amyotrophic lateral sclerosis (ALS) who uses 24-h non-invasive ventilator at home, and assisted cough through the use of the mechanical insufflation-exsufflation (MAC) device (CoughAssist, J.H. Emerson). This was essential for the removal of bronchial secretions in order to provide successful non-invasive management (and indeed less suffering for the patient) during an acute respiratory tract infection with hypoxemia and failure of manually assisted cough.

Acute Disease↗
PubMed2003

Somatostatin inhibits intestinal mucosal mast cell degranulation in normal conditions and during mast cell hyperplasia.

Several studies demonstrate that intestinal mucosal mast cells (IMMC) are modulated by nervous reflexes as well as by intraluminal content. We recently demonstrated that peptones, such as ovalbumin hydrolysate (OVH), induce the release of rat mast cell protease II (RMCP II), indicating IMMC degranulation. The response is due to complex neuroendocrine reflexes. Somatostatin (SS) and its analogues have been used as potential treatments for inflammation in other body systems with contradictory results. The aim of this study was to evaluate if somatostatin could contribute to the reduction of intestinal mucosal mast cell degranulation. Anesthetized rats were prepared for duodenal perfusion and mast cell activation was measured by analysis of RMCP II concentration in the duodenal perfusate. Somatostatin significantly decreased RMCP II concentration in both nonstimulated conditions and after ovalbumin hydrolysate perfusion. However, when somatostatin was given previously to OVH, the peptone still induced a slight increase of RMCP II. Similar effects were observed in animals previously treated with capsaicin. These protocols were repeated in animals infected with Trichinella spiralis, which induces mucosal mast cell hyperplasia. In these cases, somatostatin blocked the effect of OVH, thus, preventing an increase in RMCP II concentration. Fresh frozen tissue sections from the duodenum were processed in an attempt to demonstrate the presence of SS receptors in mast cells using immunofluorescence and Fluo-peptide labeling techniques. Confocal images from duodenum specimens demonstrate the existence of SS receptors in positive cells for RMCP II. Taken together, these results indicate that somatostatin diminishes mast cell activity and in consequence could prevent the intestinal responses to mast cell hyperplasia.

Animals↗
PubMed2003

Inducible nitric oxide synthase inhibitors ameliorate hypermotility observed after T. spiralis infection in the rat.

Trichinella spiralis infection in rodents is a well-known model of intestinal inflammation associated with hypermotility and hypersecretion. Our aim was to use this experimental model to elucidate if iNOS was involved in the development of gastrointestinal hypermotility. Rats infected with Trichinella spiralis were treated for 4 days with the nitric oxide synthase inhibitors L-NAME or L-NIL. Treatment began either simultaneously with the infection or 3 days after infection when inflammation was already fully developed. In all cases, at day 10-12 after infection, anesthetized rats were prepared with strain gauges and electrodes in the small intestine to evaluate motor activity of the small intestine. In addition, histology and iNOS immunohistochemistry studies were performed. The results showed that both NOS inhibitors blocked iNOS expression in the intestine. None of the NOS inhibitors attenuated the inflammatory process. However, the preventive treatment with L-NIL reversed hypermotility. In contrast, the treatment with NOS inhibitors 3 days after infection was not so effective in reversing motor alterations. L-NAME, but not L-NIL, caused alterations on spontaneous motility. In conclusion, these results indicate that iNOS participates in the development of motor hypermotility in the gut.

Animals↗
PubMed2003

Normal prism adaptation but reduced after-effect in basal ganglia disorders using a throwing task.

Prism adaptation is a form of visuomotor learning in which the visual and motor systems need to be adjusted because a visual perturbation is produced by horizontally displacing prisms. Despite being known for over two centuries, the neuronal substrates of this phenomenon are not yet completely understood. In this article the possible role of the basal ganglia in this kind of learning was analysed through a study of Huntington's and Parkinson's disease patients. A throwing technique requiring the use of open loop feedback was used. The variables analysed were visuomotor performance, adaptation rate and magnitude, and the after-effect. The results clearly showed that both Huntington's and Parkinson's disease groups learned at the same rate as control subjects. In addition, despite having a disturbed visuomotor performance, both experimental groups showed the same adaptation magnitude as the control group. Finally, the after-effect, which is measured after removing the prisms, is reduced in both patients groups. This reduction leads to a disruption in the normal adaptation-after-effect correlation found in normal volunteers. These results suggest that basal ganglia are not involved in this type of open-looped visuomotor learning. The large number of patients studied as well as the similarity of the findings between both populations support this hypothesis. By contrast, there is an impairment in the after-effect on both basal ganglia patient populations. This impairment may be the result of the deterioration of the perceptual recalibration process involved in visuomotor learning.

Adaptation, Ocular↗
PubMed2002

Neuroendocrine control of intestinal mucosal mast cells under physiological conditions.

Mast cells are involved in the pathogenesis of both allergies to food and inflammatory bowel disorders. In addition, there are several lines of evidence suggesting that mucosal mast cells also respond to intraluminal stimuli. Our aim was to identify neuroendocrine stimuli that could modify mucosal mast cell activity in the rat. Anaesthetized rats were prepared for duodenal perfusion and mast cell activation was measured by analysis of RMCP II concentration in the duodenal perfusate. Either buffered saline solution or a 5% ovalbumin hydrolysate (OVH) solution was infused into the duodenum. Subdiaphragmatic vagotomy or afferent ablation by intraluminal treatment with capsaicin diminished RMCP II concentration in basal conditions and significantly reduced the response to OVH, which in control animals induced a three-fold increase of the protease. The noradrenergic blockers phentholamine and propranolol significantly diminished RMCP II concentration in basal conditions and completely blocked the response to OVH. Intravenous infusion of cholecystokinin-related peptides also induced a response of mast cells. However, the response was different depending on the peptide. CCK-8 induced a slight increase of RMCP II, whereas both CCK-33 and gastrin induced a significant decrease in mast cell activity. These results show that intraluminal content modulates mucosal mast cell activity by complex mechanisms involving both nervous and endocrine pathway.

Adrenergic alpha-Antagonists↗
PubMed2002

Antinerve growth factor treatment prevents intestinal dysmotility in Trichinella spiralis-infected rats.

Nerve growth factor (NGF) could be involved in the development of hyperalgesia as well as in nervous remodeling consequence of inflammation. Both dysmotility and increase of visceral sensitivity have been described in functional gastrointestinal disorders such as irritable bowel syndrome. Trichinella spiralis-infected rats show an exacerbated spontaneous motility and a significant increase of the excitatory response to cholecystokinin (CCK), both associated with a reversible inflammatory process and the hypertrophy of the muscle layers. In this study we determined the intestinal expression of NGF mRNA by polymerase chain reaction and NGF by enzyme-linked immunosorbent assay. We implanted serosal strain gauge transducers on duodenum, jejunum, and ileum of anesthetized Sprague-Dawley rats to record circular muscle contractions. The experimental protocol included the evaluation of intestinal spontaneous motor activity (SMA), the response to CCK-8, and the ascending contraction induced by electrical mucosal stimulation. This protocol was performed in healthy and infected nontreated rats, in healthy rats with an NGF antibody treatment (1.6 mg/rat i.p.), and in infected rats with the same treatment applied at 0 or 3 days postinfection. NGF and NGF mRNA levels in the bowel were increased during inflammation. Although anti-NGF treatments did not prevent or reverse inflammatory response, the treatment was effective in preventing the motor alterations induced by the T. spiralis infection, i.e., inhibited increased SMA, reversed altered response to CCK, and reversed in part exacerbated response to electrical stimulation.

Animals↗
PubMed2000

Primary astrocytes retrovirally transduced with a tyrosine hydroxylase transgene driven by a glial-specific promoter elicit behavioral recovery in experimental parkinsonism.

We used a retroviral-mediated gene transfer system to transduce primary rat astrocytes with a transgene in which the activity of a tyrosine hydroxylase (TH) cDNA is under the transcriptional control of a human promoter of the glial fibrillary acidic protein (GFAP). The engineered cells were tested for their therapeutic efficacy in a rodent model of Parkinson's disease (PD). The method is based both on the properties of astrocytes, as well as on those of the promoter. Astrocytes are an integral part of the neural tissue, have a long life span, are more resistant to oxidative stress than neurons, and possess an efficient secretory system. The GFAP promoter is active throughout postnatal life, and its activity is up-regulated by many insults to the brain, including PD. Transduced astrocytes were implanted into the striata of rats lesioned with 6-hydroxydopamine (6-OHDA), and the efficacy of grafted cells tested. Implanted astrocytes induced a significant reduction in the turning behavior that occurs in response to apomorphine for at least 4 weeks after grafting, and transgenic mRNA and protein could be detected in implanted brains. These results indicate that the gFa2-TH construct can be readily adapted to be used with a retroviral gene transfer system to obtain nontumorigenic cells that sustain a sufficient level of transgene activity to enable therapeutic effectiveness for prolonged periods. These results further endorse the use of astrocytes for gene therapy in the central nervous system.

Animals↗
PubMed2000

Endurance training in patients with chronic obstructive pulmonary disease: a comparison of high versus moderate intensity.

PURPOSE: To create a maximum tolerated 45-minute aerobic training program for patients with chronic obstructive pulmonary disease (COPD) and to compare its outcomes with those of commonly prescribed moderate exercise. DESIGN: Prospective, randomized trial. SETTING: A work physiology laboratory. PATIENTS AND METHODS: The maximum exercise intensities that 7 COPD patients could sustain for 45 minutes were determined on a bilevel exercise ergometer. The patients then exercised 45 minutes daily, 5 days a week for 6 weeks, working 2.03+/-0.4 kJ/kg per session. They were matched with 6 COPD patients who pushed an O2 cart for 45 minutes daily, 5 days a week for 6 weeks, working 1.44+/-.35 kJ/kg per session. RESULTS: A 45 minute maximal regimen was established by alternating 1-minute peak exercise at peak VO2-levels with 4 minutes at the ventilatory anaerobic threshold or at 40% of peak VO2. Maximal bilevel training significantly decreased dyspnea at rest (p< or =.01) and the blood lactate level during submaximal exercise (p<.001), and increased peak VO2 and total physical work (p<.01), maximum inspiratory and expiratory pressures (p<.01), and grip and forearm strength and endurance (p<.01). The training also increased maximum voluntary ventilation while decreasing the ventilatory equivalent during exercise (p<.001). The O2 cart pushers significantly improved only on the 12-minute walk (p<.05). CONCLUSIONS: A maximally intense anaerobic exercise program can be created for most COPD patients that can significantly improve both skeletal and respiratory muscle strength and endurance as well as dyspnea and physiologic parameters.

Blood Gas Analysis↗
PubMed2000

Prism adaptation in normal aging: slower adaptation rate and larger aftereffect.

The effect of aging on prism adaptation, a motor learning paradigm, was evaluated. Different measures were obtained from a task consisting of throwing clay balls to a target in front of the subjects before, during, and after wearing prisms that deviate the visual field by several degrees. When performing the task without wearing the prisms, the aged subjects showed a larger hit variance, whereas the young subjects hit closer to the target. When donning the prisms, the aged group adapted more slowly than the controls, although after throwing all the balls both groups showed the same adaptation levels. After removing the prisms, the aged group showed a larger aftereffect. These findings suggest that the aftereffect requires the involvement of non-cognitive and cognitive processes and indicate that both adaptation and aftereffect are influenced by aging.

Adaptation, Physiological↗
PubMed2000

Inhibition by CCK of ascending contraction elicited by mucosal stimulation in the duodenum of the rat.

CCK released by intraluminal stimuli modifies duodenal activity contributing to a decrease in gastric emptying. However, the neural mechanisms by which CCK controls motility are not well known. The aim of this study was to investigate the interaction between CCK and the enteric nervous system through the study of the effects of CCK-8 on ascending excitation. Anaesthetized Sprague-Dawley rats were prepared with a strain-gauge sutured to the duodenum wall. An electrode holder was placed in the duodenum lumen to elicit ascending contraction. Electrical field stimulation of the duodenal mucosa (4 Hz, 0.6 ms, 30 V) induced an ascending excitation which was blocked by hexamethonium (10 mg kg-1; n=5) and atropine (0.3 mg kg-1; n=5), but enlarged by L-NNA (10(-5) mol kg-1; n=5). CCK-8 (3 ¿ 10(-9) mol kg-1 10 min-1) blocked ascending excitation and an inhibition of the induced phasic activity was observed instead (n=18). Individually, none of the CCK receptor antagonists (L-364 718 and L-365 260) (3 ¿ 10(-7) mol kg-1; n=6 each) blocked the inhibition of ascending excitation induced by CCK-8. However, simultaneous infusion of both antagonists abolished CCK-8 effect on electrical stimulation (n=5). Similarly, none of the CCK-8 agonists (A-71623, A-71378, gastrin) modified the ascending excitation. In contrast, the simultaneous infusion of A-71623 and CCK-4 (n=4) induced an effect similar to CCK-8. In conclusion, CCK-8 blocked ascending contraction elicited by electrical field stimulation of duodenal mucosa by means of simultaneous activation of CCK-A and CCK-B receptors.

Adrenergic beta-Antagonists↗
PubMed2000

In vivo changes in the intestinal reflexes and the response to CCK in the inflamed small intestine of the rat.

Functional motor changes and morphological alterations have been associated with intestinal inflammation. The aim of our study was to evaluate functional alterations of intestinal reflexes and of the responses to CCK in the Trichinella spiralis model of intestinal inflammation. Rats were prepared with strain gauges and electrodes in the small intestine to evaluate spontaneous motor activity, the ascending contraction of the peristaltic reflex, and the motor responses to CCK-8 infusion. Infected animals showed increased motor activity at the duodenum and jejunum but not at the ileum. Ascending contraction was increased in both duodenum and ileum. Ascending excitation after N(omega)-nitro-L-arginine was still increased as well as the residual response after atropine. Response to CCK-8 during intestinal inflammation was changed in the jejunum, in which it turned from the inhibition shown in healthy animals to excitation. NADPH-diaphorase staining did not show any changes between distribution and density of positive neurons in either healthy or infected animals. In conclusion, intestinal inflammation induces functional changes in the motor activity that could explain the abnormal motor responses observed in inflammatory disorders.

Animals↗