PubMed Health⌕ Search

Biomedical subjects

J Panés

Publications and source records attributed to J Panés.

At least 19 recordsLinked to original sources
PubMed2005

Anti-inflammatory effects of pancreatitis associated protein in inflammatory bowel disease.

BACKGROUND AND AIMS: Increased pancreatitis associated protein (PAP) mRNA has been reported in active inflammatory bowel disease (IBD). The aims of the current study were to characterise PAP production in IBD and the effects of PAP on inflammation. PATIENTS AND METHODS: Serum PAP levels were determined in healthy controls (n = 29), inflammatory controls (n = 14), and IBD patients (n = 171). Ex vivo PAP secretion in intestinal tissue was measured in 56 IBD patients and 13 healthy controls. Cellular origin of PAP was determined by immunohistochemistry. The effects of exogenous PAP on nuclear factor kappaB (NFkappaB) activation, proinflammatory cytokine production, and endothelial adhesion molecule expression were also analysed ex vivo. RESULTS: Patients with active IBD had increased serum PAP levels compared with controls, and these levels correlated with clinical and endoscopic disease severity. Ex vivo intestinal PAP synthesis was increased in active IBD and correlated with endoscopic and histological severity of inflammatory lesions. PAP localised to colonic Paneth cells. Incubation of mucosa from active Crohn's disease with PAP dose dependently reduced proinflammatory cytokines secretion. PAP prevented TNF-alpha induced NFkappaB activation in monocytic, epithelial, and endothelial cells and reduced proinflammatory cytokine mRNA levels and adhesion molecule expression. CONCLUSIONS: PAP is synthesised by Paneth cells and is overexpressed in colonic tissue of active IBD. PAP inhibits NFkappaB activation and downregulates cytokine production and adhesion molecule expression in inflamed tissue. It may represent an anti-inflammatory mechanism and new therapeutic strategy in IBD.

Analysis of Variance↗
PubMed2003

The 4G/4G genotype of the 4G/5G polymorphism of the type-1 plasminogen activator inhibitor (PAI-1) gene is a determinant of penetrating behaviour in patients with Crohn's disease.

BACKGROUND: Crohn's disease is a heterogeneous disorder with polygenic inheritance. AIM: To assess the effect of the 4G/5G polymorphism of the type-1 plasminogen activator inhibitor (PAI-1) gene, the major inhibitor of fibrinolysis, on Crohn's disease susceptibility and phenotype. METHODS: One hundred and fifty-seven patients with Crohn's disease and 350 controls were included prospectively. Medical records were reviewed to determine changes in the Crohn's disease phenotype. The 4G/5G polymorphism was assessed by polymerase chain reaction techniques. RESULTS: The frequencies of the 4G/4G, 4G/5G and 5G/5G genotypes were similar in patients with Crohn's disease and controls. The 4G/4G genotype (P < 0.0001; odds ratio, 4.84) and male sex (P = 0.009; odds ratio, 2.63) were independent risk factors for penetrating behaviour in Crohn's disease. Most Crohn's disease patients had a non-penetrating phenotype at diagnosis. The probability of development of a penetrating phenotype within 5 years of diagnosis was higher in patients with the 4G/4G genotype (72% vs. 19%, P < 0.0001). CONCLUSIONS: The 4G/4G genotype of the PAI-1 gene does not influence Crohn's disease susceptibility, but increases by five-fold the probability of penetrating behaviour. Most patients with the 4G/4G genotype have a non-penetrating phenotype at diagnosis, but develop a penetrating behaviour within 5 years. Genotyping the 4G/5G polymorphism may be useful for the identification of a sub-group of patients with aggressive Crohn's disease, who might benefit from specific therapy.

Adult↗
PubMed2003

Heparin mobilizes xanthine oxidase and induces lung inflammation in acute pancreatitis.

OBJECTIVE: To evaluate the effect of low molecular weight heparin on plasma xanthine oxidase concentrations and lung inflammatory response during acute pancreatitis. DESIGN: Randomized, controlled trial. SETTING: Experimental laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Acute pancreatitis was induced by intraductal administration of 5% sodium taurocholate. Low molecular weight heparin (0, 30, 90, or 300 units/kg) was administered immediately after induction of pancreatitis. MEASUREMENTS AND MAIN RESULTS: Lipase and xanthine oxidase plasma concentrations were measured 3 hrs after pancreatitis induction. Expression of P-selectin messenger RNA and myeloperoxidase activity as a marker of neutrophil infiltration were determined in the lung. An increase in xanthine oxidase plasma concentrations was observed during pancreatitis. Administration of heparin also increased plasma xanthine oxidase activity in both control and pancreatitis animals. Measures of xanthine oxidase present in the endothelial surface indicate that during pancreatitis, the enzyme is released from the gastrointestinal endothelium. By contrast, heparin mobilizes xanthine oxidase from almost all organs evaluated. Neutrophil infiltration was increased in the lung during pancreatitis. Heparin administration further increased, in a dose-dependent manner, myeloperoxidase activity and P-selectin expression in the lung in animals with pancreatitis. By contrast, in control animals, heparin had no effect on myeloperoxidase activity and did not induce P-selectin up-regulation. CONCLUSION: During acute pancreatitis, heparin administration might mobilize xanthine oxidase attached to endothelial cells, originating a free radical-generating system in the circulation that would trigger an inflammatory response in the lung.

Acute Disease↗
PubMed2002

[Frequent Internet use among Catalan patients with inflammatory bowel disease].

UNLABELLED: No data are available on the use of the Internet by Spanish patients with chronic diseases. AIM: To determine the extent to which patients with inflammatory bowel disease (IBD) in Barcelona (Spain) make use of the Internet and the relationship between Internet use and demographic characteristics. METHOD: A questionnaire on Internet use was administered to 200 patients attending an information session on IBD organized by the Gastroenterology Department of a university referral hospital in the city of Barcelona. RESULTS: Replies were received from 86% of those surveyed. The mean age was 40 years and 60% were women. Sixty-eight percent had home computers and 49% had an Internet connection. Forty-four percent sporadically or regularly obtained information on IBD from the web. A positive correlation was found between availability and Internet use and young age and higher educational level. No differences were found between men and women. Eighty-four percent expressed interest in having a web site on IBD supported by the physicians of their referral center and 65% were prepared to pay a subscription for this service. CONCLUSION: Patients with IBD from Barcelona frequently looked for information on their disease on the Internet and were receptive to initiatives concerning electronic information from physicians of their local referral center.

Adolescent↗
PubMed2002

P-selectin upregulation in bleomycin induced lung injury in rats: effect of N-acetyl-L-cysteine.

BACKGROUND: A number of adhesion molecules are involved in the process of neutrophil infiltration into the lung. P-selectin is one of these neutrophil-endothelial cell adhesion molecules. A study was undertaken to examine the involvement of P-selectin in the development of bleomycin induced inflammation and the ability of N-acetyl-L-cysteine to reduce the potential expression of this selectin in rats. METHODS: N-acetyl-L-cysteine (3 mmol/kg po) was administered daily for seven days prior to bleomycin administration (2.5 U/kg). The kinetics of P-selectin expression and the effect of N-acetyl-L-cysteine after bleomycin treatment were measured using radiolabelled antibodies. P-selectin localisation was evaluated by immunohistochemistry and neutrophil infiltration was assessed by myeloperoxidase activity. RESULTS: Bleomycin administration resulted in an upregulation of P-selectin at 1 hour, returning to baseline at 3 hours. Myeloperoxidase activity showed a significant increase at 6 hours after bleomycin administration that lasted for 3 days. N-acetyl-L-cysteine treatment completely prevented these increases. CONCLUSION: Upregulation of P-selectin in the lung is associated with neutrophil recruitment in response to bleomycin. The beneficial effect of N-acetyl-L-cysteine on bleomycin induced lung injury may be explained in part by the prevention of neutrophil recruitment in the inflammatory stage of the disease.

Acetylcysteine↗
PubMed2001

Role of P-selectin in radiation-induced intestinal inflammatory damage.

The aims of our study were to characterize the dose- and time-dependent changes in endothelial P-selectin expression and the role of this adhesion molecule as a mediator of radiation-induced inflammation. For that purpose, endothelial P-selectin expression was measured by the radiolabeled antibody technique in control and irradiated mice at 2, 6, and 24 hr following abdominal irradiation with 4 or 10 Gy; leukocyte endothelial cell interactions were assessed using intravital microscopy in intestinal venules following irradiation at the aforementioned doses and times in C57BL/6 and P-selectin-deficient mice. In wild-type mice, radiation induced a time- and dose-dependent up-regulation of P-selectin and a significant increase in the flux of rolling leukocytes 2 hr after irradiation. Irradiation induced a significant increase in leukocyte adhesion that was dose-dependent. Following irradiation, P-selectin-deficient mice did not show any increase in leukocyte rolling but did demonstrate a response in leukocyte adhesion similar to that of the wild-type mice. Radiation-induced dose-dependent histological inflammatory damage that did not differ between P-selectin-deficient and wild-type mice. We conclude that P-selectin is up-regulated following irradiation and is a key molecular determinant of leukocyte rolling but not leukocyte adhesion in this inflammatory condition. Therefore, isolated neutralization of this adhesion molecule is not an effective means for preventing radiation-induced inflammation.

Animals↗
PubMed2001

Inflammatory bowel disease: pathogenesis and targets for therapeutic interventions.

Ulcerative colitis and Crohn's disease are chronic inflammatory bowel diseases (IBDs) with a chronic relapsing course. The aetiology of these diseases remains unknown, but in the last decade an increase in experimental models of IBD has led to expansion of our understanding in various aspects of the aetiology and pathogenic mechanisms of IBD. A growing body of evidence coming from these models indicates that an immune response against gut constituents is of critical importance for intestinal inflammation and the subsequent destruction of the mucosa. For this reason, research on IBD has focused intensely on the immune and non-immune cell subsets as well as the soluble mediators involved in normal and dysregulated immune responses. An appreciation of the current knowledge of the pathogenesis of IBD is of paramount importance for the understanding of current, and development of new, treatment modalities.

Animals↗
PubMed2001

Differential role of selectins in experimental colitis.

BACKGROUND AND AIMS: The role of selectins in experimental colitis remains unknown. The aims of this study were to characterize the time-course expression of selectins in trinitrobenzene sulfonic acid (TNBS)-induced colitis, the functional role of selectins in colonic leukocyte-endothelial cell interactions, and the therapeutic usefulness of selectin blockade in this model. METHODS: Control and TNBS-induced colitic rats were studied. Expression of P- and E-selectin was assessed by the radiolabeled antibody technique, and L-selectin by flow cytometry. Leukocyte-endothelial cell interactions were studied in colonic venules by using intravital microscopy under basal conditions and after P-, E-, or L-selectin immunoblockade. Additional groups of animals were treated with anti-P-selectin antibody, a nonbinding antibody, or dexamethasone, for 7 days. RESULTS: P-selectin and E-selectin expression were markedly up-regulated in colitic rats. Increased leukocyte rolling was abrogated by anti-P-selectin, but only attenuated by anti-E- or anti-L-selectin antibodies. Only pretreatment with anti-P- selectin decreased leukocyte adhesion. Animals chronically treated with dexamethasone, but not with anti- P-selectin, had significantly lower macroscopic and histologic damage scores, colon weight, and myeloperoxidase (MPO) activity than those treated with nonbinding antibody. CONCLUSIONS: P-selectin plays a key role on leukocyte rolling and its blockade attenuates leukocyte adhesion in TNBS-induced colitis. However, treatment with an anti-P-selectin antibody does not significantly improve colitis.

Animals↗
PubMed2001

Preconditioning protects against systemic disorders associated with hepatic ischemia-reperfusion through blockade of tumor necrosis factor-induced P-selectin up-regulation in the rat.

Previous studies indicate that ischemic preconditioning protects against lung injury resulting from hepatic ischemia-reperfusion (I/R) through inhibition of tumor necrosis factor (TNF) release from Kupffer cells. The present study investigated whether this effect is limited to the lung or is a generalized systemic response and explores the molecular mechanisms involved. Hepatic I/R led to an increase in neutrophil accumulation in liver, lung, and splanchnic organs. Although preconditioning did not modify neutrophil infiltration in liver during reperfusion, it conferred protection against hepatic injury associated with I/R. In remote organs, preconditioning abrogated the increase in P-selectin up-regulation, preventing neutrophil infiltration and thus reducing the oxidative stress and microvascular disorders following hepatic I/R in these organs. Administration of Abs against P-selectin or TNF previous to ischemia had the same effects as preconditioning. The effects of preconditioning on the blockade of P-selectin up-regulation probably results from inhibition of systemic TNF release from Kupffer cells. Supplementation of TNF abolished the benefits of preconditioning, whereas the injurious effects of TNF were prevented by previous blockade of P-selectin. The results of the present study suggest that ischemic preconditioning protects the liver against I/R injury by a mechanism independent of adhesion molecule expression and neutrophil accumulation. In remote organs, however, hepatic preconditioning prevents inflammatory damage by reducing the systemic TNF release from the liver and thus preventing P-selectin up-regulation.

Animals↗
PubMed2001

123Iodine-labelled anti-VCAM-1 antibody scintigraphy in the assessment of experimental colitis.

OBJECTIVES: To evaluate the usefulness of 123I-labelled anti-vascular cell adhesion molecule-1 (VCAM-1) monoclonal antibody (MAb) scintigraphy in the assessment of colonic inflammatory damage. DESIGN: Colitis was induced by intracolonic administration of 30 mg trinitrobenzenesulphonic acid in 0.5 ml of 50% (v/v) ethanol. Rats injected with vehicle served as controls. Animals were studied at day 7 after induction of colitis. METHODS: Scintigraphy was performed in control and trinitrobenzenesulphonic acid-induced colitic rats 2, 4 and 24 h after intravenous administration of 123I-anti-VCAM-1 MAb. Scintigraphic uptake was quantified in selected areas on scintigraphs. Animals were killed, tissue 123I radioactivity accumulation was measured, and accumulation of anti-VCAM-1 MAb in each organ was calculated. 99mTc-hexamethyl propylene amine oxime-labelled leucocyte scintigraphy was performed in additional groups of animals for comparison. RESULTS: Colonic tracer uptake was visible in scans of colitic, but not control animals. Quantification of scintigraphic uptake in the colon was significantly higher in colitic rats than in control animals (P< 0.0001). The specificity of the increase was demonstrated by lack of 123I-labelled non-binding MAb uptake in the colon, and by displacement of 123I-anti-VCAM-1 MAb colonic uptake by pre-treatment with unlabelled MAb. Accumulation of anti-VCAM-1 MAb in the colon of colitic rats was eightfold higher than in control animals. Strong correlations were found between quantification of scintigraphic uptake, anti-VCAM-1 MAb accumulation, histological damage and myeloperoxidase activity in the colon. CONCLUSION: 123I-labelled anti-VCAM-1 MAb scintigraphy allows an accurate evaluation of colonic inflammatory damage in trinitrobenzenesulphonic acid-induced colitis, suggesting a potential role for this imaging technique in the assessment of human IBD.

Animals↗
PubMed2001

Role of nitric oxide in gastrointestinal inflammatory and ulcerative diseases: perspective for drugs development.

Nitric oxide is a ubiquitous molecule involved in a variety of biological processes. The specific action of NO depends on its enzymatic sources namely neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS) and inducible NOS (iNOS) and all three isoforms have been localized in the gastrointestinal tract. Constitutive synthesis of NO by nNOS or eNOS isoforms is involved in the maintaining of the gastrointestinal mucosal integrity through modulation of gastric mucosal blood flow, epithelial secretion and barrier function. However, large amounts of NO synthesized from the inducible isoform have been implicated in tissue injury in the gut during inflammatory reactions. In this review we provide an overview of the dual role of nitric oxide in modulating gastrointestinal mucosal defense and injury. In addition, we highlight the therapeutic potential of NO modulation.

Animals↗
PubMed2001

Hydrocolonic sonography for evaluating inflammatory bowel disease.

OBJECTIVE: The purpose of our study was to compare the usefulness of hydrocolonic sonography and (99m)Tc-hexamethylpropyleneamine oxime (HMPAO)--labeled leukocyte scintigraphy in the examination of patients with inflammatory bowel disease, using precise sonographic criteria of bowel involvement. SUBJECTS AND METHODS: Sixty-eight consecutive patients with active inflammatory bowel disease (34 ulcerative colitis and 34 Crohn's disease), 12 with inactive inflammatory bowel disease, and 10 control subjects were prospectively studied. Patients with active disease underwent clinical assessment, hydrocolonic sonography, scintigraphy, and colonoscopy within 72 hr, whereas patients with inactive disease and control subjects underwent clinical examination and hydrocolonic sonography. RESULTS: Involvement of a colonic segment by active inflammatory bowel disease was best defined by mucosal thickness greater than 1.5 mm, bowel wall thickness greater than 4 mm, mucosal irregularity, or the absence of haustra; and involvement of the terminal ileum by bowel wall thickness greater than 4 mm. Using these criteria, hydrocolonic sonography had 100% sensitivity for identifying patients with active inflammatory bowel disease and a greater overall accuracy (87%) than scintigraphy (77%) in the assessment of disease extension. In addition, strong correlation was shown between a hydrocolonic sonography activity index and clinical and endoscopic activity indexes. CONCLUSION: This prospective study provides precise sonographic criteria for the definition of bowel involvement by active inflammatory bowel disease. Hydrocolonic sonography has a greater accuracy than scintigraphy for assessing disease extension and activity. Therefore, hydrocolonic sonography should be considered a first-choice technique to complete the study of inflammatory bowel disease after confirmation of the diagnosis by histology.

Adolescent↗
PubMed2001

Brain endothelial adhesion molecule expression in experimental colitis.

OBJECTIVES: 1) To determine if endothelial expression of adhesion molecules involved in leukocyte recruitment is increased in the brain and other organs in four different models of experimental colitis, and 2) to investigate whether leukocyte infiltration occurs in the brain of colitic animals. METHODS: Endothelial vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) expression was quantified, using the dual radiolabeled antibody technique in rats with trinitrobenzenesulfonic acid (TNBS)-induced colitis, in mice with dextran sulfate sodium (DSS)-induced colitis, in SCID mice reconstituted with CD45RBhigh T-cells, and in IL-10-/- mice. Leukocyte infiltration in the brain of TNBS-induced colitic rats was assessed by myeloperoxidase activity and immunohistochemical staining with anti-CD45 monoclonal antibody. RESULTS: Marked upregulation of brain endothelial VCAM-1 (2- to 5.5-fold) was consistently found in colitic animals in the four models studied. Brain VCAM-1 strongly correlated with colon VCAM-1 and colon weight. By contrast, upregulation of brain ICAM-1 in colitic animals was only observed in the CD45RBhigh transfer (3-fold) and the TNBS-induced (1.5-fold models). Heart and muscle VCAM-1 and ICAM-1 were not upregulated in colitic animals in the majority of models studied. There was no leukocyte infiltration into the brain of TNBS-induced colitic rats. CONCLUSIONS: Our study demonstrates a marked and specific upregulation of endothelial VCAM-1 in the brain of colitic animals. This activation of cerebral endothelial cells was not associated with an infiltration of leukocytes into brain tissue.

Animals↗