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Biomedical subjects

A Salas

Publications and source records attributed to A Salas.

At least 73 records · Page 4Linked to original sources
PubMed1999

Differential effects of a nitric oxide donor on reperfusion-induced microvascular dysfunction in diabetic and non-diabetic rats.

AIMS/HYPOTHESIS: Diabetes is associated with a high incidence of ischaemic disease and impaired nitric oxide responses. Therefore, the aim of the present study was to assess the effect of nitric oxide on ischaemia/reperfusion (I/R)-induced microvascular responses in an experimental model of diabetes. METHODS: Leucocyte-endothelial cell interactions were studied in mesenteric venules after superior mesenteric artery occlusion (10 min), at 10 and 30 min of reperfusion in control and streptozotocin-induced diabetic rats. An oxidant-sensitive fluorochrome was used to measure oxidant production during reperfusion. P-selectin and ICAM-1 expression were quantified at 10 and 30 min of reperfusion respectively, using radiolabelled monoclonal antibodies. The transcription of ICAM-1 mRNA was determined by northern blot. The effect of spermine NONOate, given locally, on all variables studied, was assessed in additional experiments. RESULTS: Ischaemia/reperfusion induced an enhanced leucocyte accumulation and oxidant production in diabetic animals. Moreover, I/R enhanced endothelial P-selectin expression in both groups of animals, whereas it only up regulated ICAM-1 endothelial expression and mRNA expression in diabetic rats. Spermine NONOate abrogated to a similar extent leucocyte adhesion and emigration in control and diabetic animals, although the mechanisms underlying this protective effect appear to be different. In control rats Spermine NONOate effectively prevented P-selectin up regulation, whereas in diabetic rats NO appreciably attenuated the rapid up regulation of ICAM-1 by preventing its transcription. CONCLUSIONS/INTERPRETATION: Expression of ICAM-1 is rapidly increased in diabetic, but not control, animals exposed to I/R. The increased endothelial cell adhesion molecule expression, leucocyte-endothelial cell adhesion and oxidant stress induced by I/R in diabetic rats are significantly attenuated by exogenous NO. [Diabetologia (1999) 42: 1350-1358]

Animals↗
PubMed1999

Role of P-selectin and ICAM-1 in pancreatitis-induced lung inflammation in rats: significance of oxidative stress.

OBJECTIVE: To investigate the role of P-selectin and intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of lung injury associated with pancreatitis, and the relation between xanthine oxidase-derived oxidants and expression of these adhesion molecules. SUMMARY BACKGROUND DATA: In acute pancreatitis, acute respiratory distress syndrome occurs in the early stages of disease. This process is mediated by neutrophil infiltration. METHODS: Pancreatitis was induced in rats by intraductal administration of 5% sodium taurocholate. ICAM-1 and P-selectin expression was measured using radiolabeled monoclonal antibodies. Neutrophil infiltration and plasma levels of xanthine oxidase were also evaluated. RESULTS: Pancreatitis induces increases in P-selectin expression in lung, whereas ICAM-1 is unchanged from baseline levels. Immunoneutralization of either P-selectin or ICAM-1 prevents the infiltration of neutrophils into the lung. Xanthine and xanthine oxidase activity were increased after induction of pancreatitis. Xanthine oxidase inhibition prevents the upregulation of P-selectin in lung and neutrophil infiltration. CONCLUSIONS: During acute pancreatitis, P-selectin is upregulated in the pulmonary endothelium and is a key determinant of leukocyte recruitment. Constitutive ICAM-1 is also involved in the process of cell infiltration into the lung. The increased expression of P-selectin appears to be triggered by a mechanism dependent on free radicals generated by xanthine oxidase released by the damaged pancreas.

Acute Disease↗
PubMed1999

Incidence of collagenous and lymphocytic colitis: a 5-year population-based study.

OBJECTIVE: The incidence of collagenous and lymphocytic colitis is not well known. We sought to assess the incidence of collagenous and lymphocytic colitis in a well-defined population during a 5-yr study period. METHODS: From January 1, 1993, to December 31, 1997, all new patients diagnosed with collagenous or lymphocytic colitis living in the catchment area of the Hospital Mutua de Terrassa (Barcelona, Spain) were identified. Since 1993 all patients with chronic diarrhea were referred for a diagnostic colonoscopy. Multiple biopsy sampling of the entire colon was performed when appearance of the colonic mucosa was grossly normal. RESULTS: Twenty-three cases of collagenous colitis and 37 of lymphocytic colitis were diagnosed. The female:male ratios were 4.75:1 and 2.7:1 for collagenous and lymphocytic colitis, respectively. The mean age at onset of symptoms was 53.4+/-3.2 (range, 29-82) yr for collagenous colitis, and 64.3+/-2.7 (range, 28-87) yr for lymphocytic colitis (p = 0.012). The mean annual incidence per 100,000 inhabitants based on the year of onset of symptoms was 1.1 (95% confidence interval [CI], 0.4-1.7) for collagenous colitis, and 3.1 (95% CI, 2.0-4.2) for lymphocytic colitis. A peak incidence was observed in older women in both diseases. A rate of microscopic colitis of 9.5 per 100 normal-looking colonoscopies performed in patients with chronic watery diarrhea was observed. Normal rectal biopsies were found in 43 % and 8% of patients with collagenous and lymphocytic colitis, respectively. CONCLUSIONS: The incidence of lymphocytic colitis is three times higher than that of collagenous colitis. Microscopic colitis should be considered as a major possibility in the work-up of chronic diarrhea in older women.

Age Factors↗
PubMed1999

Myofibroblast proliferation, fibrosis, and defective pancreatic repair induced by cyclosporin in rats.

BACKGROUND: Full recovery is always achieved after caerulein induced pancreatitis. Cyclosporin stimulates transforming growth factor beta (TGF-beta) and may interfere with pancreatic regeneration. AIM: To investigate the effects of cyclosporin after caerulein induced pancreatitis or after caerulein injury. METHODS: Protocol A: rats received cyclosporin daily (20 mg/kg) and caerulein pancreatitis was induced on days 2 and 8. Protocol B: six courses of caerulein pancreatitis were induced at weekly intervals. Cyclosporin was administered on induction and the day before. Rats recovered for two weeks before being killed. Control groups received saline, cyclosporin, or caerulein alone. RESULTS: Protocol A: plasma TGF-beta1 and tissue collagenase rose after pancreatitis but decreased towards baseline values on day 15, matching a low collagen content. Morphology disclosed minimal inflammatory infiltration and some interstitial cells immunoreactive for smooth muscle alpha-actin (SMA). TGF-beta1 increased, and remained high in cyclosporin treated groups (cyclosporin alone and cyclosporin plus caerulein). Rats treated with cyclosporin and caerulein showed severe pancreatic weight reduction, abundant inflammatory infiltrates, increased SMA immunoreactive interstitial cells, high collagen content, and delayed collagenase response. No SMA immunoreactive cells were detected in normal rats. Cyclosporin alone also increased SMA immunoreactive cells, despite the absence of inflammatory infiltration and fairly conserved pancreatic structure. Protocol B: the combined pulse treatment induced appreciable collagen deposition and resulted in a smaller pancreas than controls. Morphological examination showed atrophy, fibrosis, fibroblast proliferation, and mononuclear infiltrates. CONCLUSION: Cyclosporin greatly distorts pancreatic repair, transforming caerulein induced pancreatitis into a fibrotic chronic-like disease. The mechanism involves TGF-beta, myofibroblasts, and defective collagenase activation.

Actins↗
PubMed1999

Dexamethasone inhibition of leucocyte adhesion to rat mesenteric postcapillary venules: role of intercellular adhesion molecule 1 and KC.

BACKGROUND: A previous study showed that the glucocorticoid dexamethasone, at doses of 100 microg/kg and above, inhibited leucocyte adhesion to rat mesenteric postcapillary venules activated with interleukin 1beta (IL-1beta), as assessed by videomicroscopy. AIMS: To identify whether the adhesion molecule, intercellular adhesion molecule 1 (ICAM-1), or the chemokine KC could be targeted by the steroid to mediate its antiadhesive effect. METHODS: Rat mesenteries were treated with IL-1beta (20 ng intraperitoneally) and the extent of leucocyte adhesion measured at two and four hours using intravital microscopy. Rats were treated with dexamethasone, and passively immunised against ICAM-1 or KC. Endogenous expression of these two mediators was validated by immunohistochemistry, ELISA, and the injection of specific radiolabelled antibodies. RESULTS: Dexamethasone greatly reduced IL-1beta induced leucocyte adhesion, endothelial expression of ICAM-1 in the postcapillary venule, and release of the mast cell derived chemokine KC. Injection of specific antibodies to the latter mediators was also extremely effective in downregulating (>80%) IL-1beta induced leucocyte adhesion. CONCLUSIONS: Induction by IL-1beta of endogenous ICAM-1 and KC contributes to leucocyte adhesion to inflamed mesenteric vessels. Without excluding other possible mediators, these data clearly show that dexamethasone interferes with ICAM-1 expression and KC release from mast cells, resulting in suppression of leucocyte accumulation in the bowel wall, which is a prominent feature of several gastrointestinal pathologies.

Animals↗
PubMed1999

Association between coffee drinking and K-ras mutations in exocrine pancreatic cancer. PANKRAS II Study Group.

STUDY OBJECTIVE: To analyse the relation between coffee consumption and mutations in the K-ras gene in exocrine pancreatic cancer. DESIGN: Case-case study. Consumption of coffee among cases with the activating mutation in the K-ras gene was compared with that of cases without the mutation. SETTING AND PATIENTS: All cases of pancreatic cancer newly diagnosed at five hospitals in Spain during three years were included in the PANKRAS II Study (n = 185, of whom 121 whose tissue was available for molecular analysis are the object of the present report). Over 88% were personally interviewed in hospital. DNA was amplified from paraffin wax embedded tissues, and mutations in codon 12 of K-ras were detected by the artificial RFLP technique. MAIN RESULTS: Mutations were found in tumours from 94 of 121 patients (77.7%). Mutations were more common among regular coffee drinkers than among non-regular coffee drinkers (82.0% v 55.6%, p = 0.018, n = 107). The odds ratio adjusted by age, sex, smoking and alcohol drinking was 5.41 (95% CI 1.64, 17.78). The weekly intake of coffee was significantly higher among patients with a mutated tumour (mean of 14.5 cups/week v 8.8 among patients with a wild type tumour, p < 0.05). With respect to non-regular coffee drinkers, the odds ratio of a mutated tumour adjusted by age, sex, smoking and alcohol drinking was 3.26 for drinkers of 2-7 cups/week, 5.77 for drinkers of 8-14 cups/week and 9.99 for drinkers of > or = 15 cups/week (p < 0.01, test for trend). CONCLUSIONS: Pancreatic cancer cases without activating mutations in the K-ras gene had drank significantly less coffee than cases with a mutation, with a significant dose response relation: the less they drank, the less likely their tumours were to harbour a mutation. In exocrine pancreatic cancer the K-ras gene may be activated less often among non-regular coffee drinkers than among regular drinkers. Caffeine, other coffee compounds or other factors with which coffee drinking is associated may modulate K-ras activation.

Adolescent↗
PubMed1999

Mechanisms underlying the anti-inflammatory actions of central corticotropin-releasing factor.

Immune activation of hypothalamic corticotropin-releasing factor (CRF) provides a negative feedback mechanism to modulate peripheral inflammatory responses. We investigated whether central CRF attenuates endothelial expression of intercellular adhesion molecule 1 (ICAM-1) and leukocyte recruitment during endotoxemia in rats and determined its mechanisms of action. As measured by intravital microscopy, lipopolysaccharide (LPS) induced a dose-dependent increase in leukocyte rolling, adhesion, and emigration in mesenteric venules, which was associated with upregulation of endothelial ICAM-1 expression. Intracisternal injection of CRF abrogated both the increased expression of ICAM-1 and leukocyte recruitment. Intravenous injection of the specific CRF receptor antagonist astressin did not modify leukocyte-endothelial cell interactions induced by a high dose of LPS but enhanced leukocyte adhesion induced by a low dose. Blockade of endogenous glucocorticoids but not alpha-melanocyte-stimulating hormone (alpha-MSH) receptors reversed the inhibitory action of CRF on leukocyte-endothelial cell interactions during endotoxemia. In conclusion, cerebral CRF blunts endothelial upregulation of ICAM-1 and attenuates the recruitment of leukocytes during endotoxemia. The anti-inflammatory effects of CRF are mediated by adrenocortical activation and additional mechanisms independent of alpha-MSH.

Adrenalectomy↗
PubMed1998

Parosteal osteoma of the iliac bone.

A 33-year-old patient with a 2-year history of intermittent pain in the right gluteal region and thigh presented with a large sclerotic lesion of the iliac bone. From the findings on radiography, scintigraphy, CT and MRI, a giant parosteal osteoma was suspected. The histological examination confirmed the diagnosis. Since the lesion was extensive it was observed with periodic follow-up examinations. At present, 5 years after the diagnosis, the patient is asymptomatic and imaging studies show that the lesion persists with reduction of sclerosis and size. The tumor was on the surface as well as intramedullary--only one other case with such a distribution is known to us--and it was also in the iliac bone.

Adult↗
PubMed1998

Sequence variation of a hypervariable short tandem repeat at the D1S1656 locus.

A short tandem repeat at the D1S1656 locus was sequenced in 45 selected alleles and 13 different alleles were found which were designated according to the total number of repeats. This STR is a compound hypervariable STR consisting of blocks of (TAGR) repeats with a basic sequence structure (TAGA)4(TGA)0-1(TAGA)6-16(TAGG)0-1(TG)5. The presence of a TGA, probably due to an A deletion in the fifth TAGA repeat leads to intermediate a.3 alleles. Population data showed that this is a highly polymorphic STR with a heterozygosity of more than 0.89. This fact together with its simple structure and small size (129-168 bp) makes this STR one of the most interesting DNA polymorphisms for forensic and genetic purposes.

Alleles↗
PubMed1998

Sequence variation of a variable short tandem repeat at the D18S535 locus.

A short tandem repeat in the D18S535 locus was sequenced in 25 selected alleles. A total of 8 different alleles were found which can be designated according to the total number of repeats. This STR is a simple hypervariable STR consisting of blocks of (GATA) repeats with a basic sequence structure (GATA)1(GACA)1(GATA)1 (GAT)1(GATA)9-16. Population data showed that this is a highly polymorphic STR with a heterozygosity of more than 0.80, a simple structure and small size (130-158 bp) which makes this an interesting DNA polymorphism for forensic and genetic purposes.

DNA↗
PubMed1998

Stimulation of transforming growth factor beta1 by enteric bacteria in the pathogenesis of rat intestinal fibrosis.

BACKGROUND & AIMS: Bacteria and their products stimulate inflammatory responses. Certain mediators, such as transforming growth factor beta1 (TGF-beta1), induce collagen synthesis. Excess collagen deposition results in bowel strictures. The aim of this study was to investigate the role of bacteria and TGF-beta1 in the pathogenesis of intestinal fibrosis. METHODS: In rats with colitis, the effects of bowel decontamination with antibiotics on TGF-beta1, tumor necrosis factor alpha (TNF-alpha), and collagen content in colonic tissue were studied. In normal rats, bacteria of the predominant flora were inoculated into the colonic wall. The effect of neutralizing antibody to TGF-beta1 on tissue collagen deposition was studied. RESULTS: Rats with chronic colitis showed increased levels of TGF-beta1, TNF-alpha, and collagen in the tissue and a high rate of bowel strictures. Antibiotic treatment significantly prevented the increase in TGF-beta1 and collagen and the formation of strictures. Inoculation of bacterial suspensions into the colonic wall increased tissue TGF-beta1 and collagen content. Neutralizing antibody to TGF-beta1 prevented collagen deposition. Colonic wall inoculations with single anaerobic strains (Clostridium ramosum, Bacteroides fragilis, and Bacteroides uniformis), but not with aerobes, induced collagen deposition. CONCLUSIONS: Certain strains of the common flora stimulate TGF-beta1 and induce deposition of collagen in the colonic wall.

Animals↗
PubMed1998

New melampolides from Schkuhria schkuhrioides.

The novel melampolides (11R)-11,13-dihydro-schkuhriolide (7), (11S)-11,13-dihydro-schkuhriolide (8), and schkuhrioidiol (11), along with the known constituents, frutescin (1), schkuhriolide (2), frutescinic acid (4), allo-schkuhriolide (5), and epoxyschkuhriolide (6) were isolated from the aerial parts of Schkuhria schkuhrioides. The structures of the new compounds were determined by spectroscopic methods. Compounds 1, 2, 4, 5, and 6 displayed no significant cytotoxic or antimicrobial activities.

Animals↗
PubMed1998

Effects of steroid treatment on activation of nuclear factor kappaB in patients with inflammatory bowel disease.

Nuclear factor kappB (NFkappaB) is a transcription factor that controls several genes important for immunity and inflammation. The aim of this study was to assess if activation of NFkappaB plays a role in the pathogenesis of inflammatory bowel disease (IBD), and whether steroid treatment affects NFkappaB activation. Activation of NFkappaB was analysed in colon biopsy samples of 13 patients with active IBD (8 Crohn's colitis, 5 ulcerative colitis) by electrophoretic mobility-shift assays, under basal conditions and 3 weeks after treatment with 0.75 mg kg(-1) day(-1) prednisolone. The presence of interleukin-8 mRNA in biopsies was assessed by RT-PCR. A specific NFkappaB band was present in all nuclear extracts from inflamed mucosa, whereas the band was barely detectable in uninflamed colonic mucosa. NFkappaB bands were super-shifted by antibodies against p50 subunit, whereas antibodies against p65, p52, c-Rel, or Rel B did not modify the mobility of the band. Increased interleukin-8 mRNA was detected at the same sites of NFkappaB activation. Steroid-induced healing of colonic inflammation was associated with disappearance of NFkappaB from nuclear extracts. These results support the notion that NFkappaB plays an important role in the pathogenesis of IBD, and that blockade of NFkappaB activation is one of the mechanisms by which steroids suppress the inflammatory cascade in IBD.

Adult↗
PubMed1998

Derangement of mucosal barrier function by bacteria colonizing the rat colonic mucosa.

BACKGROUND: Interaction between gut flora and the intestinal barrier may involve changes in permeability. METHODS: Rats with a colonic segment excluded from faecal transit were surgically prepared. Matched groups were either kept on luminal antibiotics to prevent colonization of the segment or recolonized with mixed rat flora. Permeability to low-dose trinitrobenzenesulphonic acid (TNBS) or trinitrophenol (TNP), and mucosal injury by the compounds at a high dose were tested in antibiotic and recolonized rats (the compounds differ in water solubility but share a common antigenic domain). RESULTS: Lumen to blood clearance of the hydrophilic probe (TNBS) was faster in recolonized than in antibiotic rats. The hydrophobic compound TNP was absorbed at faster rates than TNBS, but there was no difference between antibiotic and recolonized rats. Instillation of TNBS at a high dose induced mucosal release of inflammatory mediators and tissue myeloperoxidase accumulation in recolonized rats but not in antibiotic rats. Large necrotic lesions with submucosal involvement after TNBS were only observed in recolonized rats. In contrast, TNP induced mucosal inflammation and large lesions with submucosal necrosis both in recolonized and in antibiotic rats. CONCLUSION: Colonizing bacteria may increase intestinal permeability to hydrophilic compounds and render the mucosa susceptible to injury.

Animals↗
PubMed1998

Randomized clinical trial comparing two one-week triple-therapy regimens for the eradication of Helicobacter pylori infection and duodenal ulcer healing.

OBJECTIVE: One-week triple therapy has been shown to be effective in Helicobacter pylori eradication and duodenal ulcer healing. However, the optimal therapeutic combination has not yet been identified. Bismuth-containing regimens have the advantage of requiring only one antibiotic. It has been suggested that high doses of omeprazole improve the bactericidal efficacy of antimicrobial regimens against H. pylori. We evaluated the efficacy of two 1-wk triple-therapy regimens for H. pylori eradication and duodenal ulcer healing. METHODS: On an intention-to-treat basis, 182 patients with H. pylori-associated duodenal ulcer were randomized. Group OCB patients (n = 91) were given omeprazole 40 mg b.i.d., clarithromycin 500 mg b.i.d., and colloidal bismuth subcitrate 120 mg q.i.d. for 7 days. Group OCA patients (n = 91) were treated with omeprazole and clarithromycin at the same doses plus amoxicillin 1 g b.i.d., also for 7 days. Endoscopies were performed at entry and at 4 wk after the end of treatment. The presence of H. pylori was assessed by urease test, histology, Gram stain, and culture. No patient received follow-up treatment. RESULTS: H. pylori eradication rates achieved in the OCB and OCA groups were similar whether by intention-to-treat (82.4% vs 88.9% ;p = 0.21) or per protocol analysis (83.3% vs 89.9%; p = 0.19). Duodenal ulcer healing rates also were the same for OCB and OCA in intention-to treat (91.2% vs 91.1%) and per protocol analysis (92.2% vs 92.1%), respectively (p = 0.98). CONCLUSIONS: High rates of H. pylori eradication and duodenal ulcer healing were obtained with both short-treatment regimens, which were safe and well-tolerated. Colloidal bismuth subcitrate seems to be a good alternative to amoxicillin in the triple-therapy combination with omeprazole and clarithromycin. The omeprazole dose does not seem to play a major role in H. pylori eradication in these therapeutic combinations.

Adult↗
PubMed1998

Mechanisms responsible for enhanced inflammatory response to ischemia-reperfusion in diabetes.

The objective of the present study was to assess the role of lipid mediators and adhesion molecule expression in exacerbation of ischemia-reperfusion-induced inflammatory response in diabetes. Leukocyte-endothelial cell interactions were studied in mesenteric venules by intravital microscopy. Endothelial expression of intercellular adhesion molecule (ICAM)-1 was measured by the double-radiolabeled monoclonal antibody technique, and beta2-integrin expression was measured by flow cytometry. Ischemia-reperfusion elicited significantly larger increases in leukocyte adhesion and emigration in diabetic rats that were prevented by a platelet-activating factor (PAF)-receptor antagonist or a leukotriene synthesis inhibitor. Leukotriene B4 (LTB4) superfusion induced similar leukocyte recruitment in diabetic and control rats, whereas PAF elicited larger increases in diabetic rats. CD11a, but not CD11b, expression was higher in leukocytes from diabetic animals. Endothelial ICAM-1 in mesentery and in intestine did not differ between diabetic and control rats. These results indicate that diabetes is associated with an enhanced response to ischemia-reperfusion that depends on both PAF and leukotrienes. An increased sensitivity to PAF, along with an increased CD11a expression, may account for the exaggerated inflammatory response to ischemia-reperfusion in diabetes.

Animals↗