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Biomedical subjects

A Salas

Publications and source records attributed to A Salas.

At least 91 records · Page 5Linked to original sources
PubMed1998

Antitumor necrosis factor therapy in rat chronic granulomatous colitis: critical dose-timing effects on outcome.

Inhibition of tumor necrosis fact (TNFalpha) is of potential benefit in the treatment of chronic inflammatory conditions. However, TNFalpha plays an important role in host defenses against infection, and blocking TNFalpha production may also have adverse effects. We tested the efficacy and safety of anti-TNFalpha therapy in experimental colitis induced by trinitrobenzenesulfonic acid. We cultured colonic wall specimens for bacterial growth and measured native TNFalpha protein synthesis in colonic tissue at days 0, 1, 4, 10 and 18 after induction of colitis. Anti-TNFalpha therapy (monoclonal g1 immunoglobulin, 15 mg/kg i.p., every third day) was started on either day 4 or day 10 after induction of colitis. On day 18, we measured the release of inflammatory mediators and scored colonic lesions. In acute lesions, several species of the common flora were grown, including Streptococcus, Staphylococcus, Bacteroides, clostridia and enterobacteria. In chronic lesions, only enterobacteria, clostridia and lactobacilli were isolated. TNFalpha production by inflamed colonic tissue was increased in both acute and chronic lesions. Anti-TNFalpha therapy induced a significant decrease in the release of inflammatory mediators and histopathological remission when treatment started on day 10. However, anti-TNFalpha therapy increased eicosanoid release and lesion scores when treatment started on day 4. In conclusion, acute colonic lesions showed polymicrobial infection. Anti-TNFalpha therapy induced remission of chronic intestinal inflammation, but early treatment did not prove effective.

Animals↗
PubMed1997

Rapid and enhanced detection of mitochondrial DNA variation using single-strand conformation analysis of superposed restriction enzyme fragments from polymerase chain reaction-amplified products.

A strategy is described for detecting mitochondrial (mt) DNA variation which permits rapid and straightforward screening for forensic purposes. The method is based on the selection of fragments with adequate length for performing single strand conformation polymorphism (SSCP) analysis selecting a set of restriction enzymes (RE) which yield fragments with prefixed lengths. After digestion of mtDNA by the appropriate enzyme or set of enzymes, SSCP analysis is performed in a semiautomatic electrophoretic system using a silver staining detection method. The conformational changes due to single mutations were therefore found not to change the electrophoretic protocol but to change the relative position of the mutations within the fragment. The discrimination power of this method is estimated to be 90% when two restriction enzymes (MspI and HinfI) are used, but it is considerably higher when other enzymes are added.

DNA Mutational Analysis↗
PubMed1997

Incrimination of anaerobic bacteria in the induction of experimental colitis.

Commensal bacteria may participate in the pathogenesis of bowel inflammation. We studied the role of bacteria from the rat colonic flora on transmural inflammation induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). First, bacterial translocation to the colonic wall after induction of colitis was assessed by microbiological and histological methods. Second, rats with a colonic segment excluded from fecal transit were prepared for recolonization with preselected bacteria and used to test the effects of different species on inflammation (eicosanoid release, tissue myeloperoxidase) and damage (histology). Six strains (three aerobes and three anaerobes) were identified in colonic tissue 24 h after induction of colitis. Acridine staining showed bacteria in necrotic areas of the mucosa and invading the submucosa. Rats with excluded colon and sterile culture of luminal washings showed mild inflammation and low mucosal damage in response to TNBS. Rats colonized with anaerobes showed significantly higher eicosanoid release than rats colonized with aerobes only. Moreover, submucosal-lesions were mostly observed in rats with anaerobes. Our findings suggest that colonic anaerobes play a key role in transmural inflammation.

Animals↗
PubMed1997

Immunofluorometric assay of pepsinogen C and preliminary clinical applications.

We developed mouse monoclonal antibodies (Abs) against pepsinogen C with highly purified antigen isolated from gastric mucosa. The Abs were used to construct a two-site sandwich-type assay for pepsinogen C with time-resolved fluorometry as a detection technique. The assay has a detection limit of 0.1 microgram/L and is precise (within-run and day-to-day CVs < 11%). We used this assay to measure pepsinogen C in seminal plasma, breast cyst fluid, amniotic fluid, male and female serum, serum from patients with prostate cancer, urine, breast tumor cytosolic extracts, breast milk, and cerebrospinal fluid. Highest pepsinogen C concentrations were in seminal plasma, followed by breast cyst fluid and amniotic fluid. We found no correlation between prostate-specific antigen concentrations and concentrations of pepsinogen C in serum of prostate cancer patients, and concluded that this marker is not useful for either diagnosing or monitoring prostatic carcinoma. The availability of a highly sensitive, reliable, and convenient method for quantifying pepsinogen C will allow investigations into the possible diagnostic value of this analyte in various clinical conditions, including benign breast diseases, breast cancer, fertility, and pregnancy.

Amniotic Fluid↗
PubMed1996

Sequence variation of a hypervariable short tandem repeat at the D12S391 locus.

A short tandem repeat (STR) in the D12S391 locus was sequenced in more than 40 individuals. Twenty different alleles were found and these could be grouped into 12 allelic classes in accordance with the total number of repeats. This is a compound STR consisting of blocks of (AGAT) and (AGAC) repeats with basic sequence structure (AGAT)8-17(AGAC)6-10(AGAT)0-1. Whereas smaller alleles (15-18) have variation limited to the (AGAT) unit, in larger alleles the complexity is greater with variation in the number of tandem arrays in the two motifs (AGAT) and (AGAC). Population data showed that this is a highly polymorphic STR with a heterozygosity of more than 0.9. This fact, together with its simple structure, makes this STR an interesting DNA polymorphism for forensic and genetic purposes.

Alleles↗
PubMed1996

Diagnosis of ascending aortic dissection by transesophageal echocardiography: utility of M-mode in recognizing artifacts.

OBJECTIVES: This study sought to assess the reliability of biplanar transesophageal echocardiography in the diagnosis of ascending aortic dissection and to test the utility of M-mode information in the differential diagnosis of ascending aortic ultrasound artifacts and intimal flap images. BACKGROUND: Transesophageal echocardiography is a useful technique in the diagnosis of aortic dissection. However, ultrasound artifacts in the ascending aorta are an important limitation. METHODS: Transesophageal echocardiography was performed in 132 consecutive patients with clinically suspected aortic dissection. Two-dimensional and M-mode echocardiography and color Doppler were used to diagnose intimal flap and artifact images. Diagnoses were validated either anatomically or with reference techniques. RESULTS: The sensitivity and specificity of transesophageal echocardiography in the diagnosis of ascending aortic dissection were 96.8% and 100%, respectively. Ninety-three artifacts were observed in 56 (55%) of 101 patients without ascending aortic dissection. Two-dimensional echocardiography easily identified 74 artifacts (80%). Color Doppler showed no ascending flow abnormalities in 71% of artifact images. M-mode echocardiography showed three location and mobility artifact patterns related to the posterior wall of the aorta or the right pulmonary artery. In contrast, intimal flap movement showed no relation to the aortic wall movement in 25 cases (83%). Blind analysis of transesophageal echocardiographic study tapes underlined the utility of M-mode in the differential diagnosis. Ranges of sensitivity, specificity and positive predictive value (established by including doubtful results as either positive or negative) improved from 87.1-93.5% to 93.5-96.8%, from 85.1-94.1% to 99-100% and from 65.9-81.8% to 96.8-100%, respectively, with the inclusion of M-mode data. CONCLUSIONS: Biplanar transesophageal echocardiography permits reliable diagnosis of ascending aortic dissection. Ultrasound artifacts are common, but assessment of the location and mobility of intraluminal images by M-mode echocardiography definitely improves diagnostic accuracy.

Adolescent↗
PubMed1996

Induction of chronic pancreatic disease by trinitrobenzene sulfonic acid infusion into rat pancreatic ducts.

Despite being a common disease in humans, little is known about the etiopathogenesis of and effective therapeutic approaches to chronic pancreatitis, due mainly to the fact that few simple animal models suitable to study inflammatory and fibrogenetic processes have been described in the pancreas. Trinitrobenzene sulfonic acid (TNBS) induces chronic colitis and cholangitis in the rat. We hypothesized that TNBS instillation into the pancreatic ducts could also result in the development of a chronic pancreatic disease. The biliopancreatic duct of rats was cannulated and tied close to the liver. TNBS [0.4 ml of 2% TNBS in phosphate-buffered saline (PBS)-10% ethanol, pH 8] was infused into the pancreas under a continuous controlled-pressure system. Control rats underwent the same procedure using vehicle only. Pathology assessment of TNBS-treated rats examined at 48 h was consistent with severe acute necrotizing pancreatitis, having a morality rate of 31% and serum amylase activity of 37.4 +/- 8.8 U/ml at 24 h and 13.3 +/- 1.7 U/ml at 48 h (p < 0.01 for both time points compared to PBS/ethanol-treated rats). Groups of 10 rats each were killed at 3, 4, and 6 week after the surgical procedure. Morphological examination revealed changes mimicking features of chronic pancreatitis in humans in 80% (32 of 40) of TNBS-treated rats, consisting in various degrees of periductal and lobular fibrosis, duct stenosis, patchy acute and chronic inflammatory cell infiltrates, and signs of gland atrophy. Animals developing chronic disease had a weight gain rate significantly lower than that of control rats. Serum amylase, fasting glucose, and a glucose tolerance test were not different in diseased or control rats. In conclusion, we were able to induce chronic fibrogenetic inflammatory disease in the pancreas after a single pulse instillation of TNBS into the pancreatic ducts. This might be a useful animal model to study the pathophysiology of inflammatory, fibrogenetic, and reparative processes in pancreatic tissue.

Amylases↗
PubMed1996

Toxic dilatation of colon in a rat model of colitis is linked to an inducible form of nitric oxide synthase.

The contribution of nitric oxide (NO) to the altered colonic contractility of acute colitis was investigated in the 2,4,6-trinitroben-zenesulfonic acid model. NO synthase was measured in colonic tissue; the effects of NO synthase inhibition on colonic contractility were studied in vitro and in vivo. Inducible NO synthase was not detected in normal colons, whereas inflamed colons showed high activity. Acute inflammation was associated with enlarged colonic perimeter. NO synthase inhibitors or selective inhibitors of the inducible enzyme prevented colonic dilatation. In vitro, contractile responses to KCl were lower in muscle from colitic than control rats. After NO synthase inhibition, however, no difference was observed between colitic and control muscle contractility. In vivo, intracolonic pressure was lower in colitic than in control rats. Selective inhibition of inducible NO synthase increased intracolonic pressure in colitic but not in control rats. In conclusion, NO generation by inducible enzymes impairs smooth muscle contractility in colitis and may be involved in the pathogenesis of toxic dilatation of the colon.

Animals↗
PubMed1996

[Pseudomonas spp. infections in patients with HIV infections].

BACKGROUND: The aim of this study was to describe the characteristics of the infections by Pseudomonas spp. observed in patients with HIV infection in Spain. METHODS: A retrospective study was performed of the isolations of Pseudomonas spp. in microbiologic samples of patients with HIV infection in three hospitals from Mallorca, Spain, since 1986. RESULTS: Twenty-nine patients with some positive culture for Pseudomonas were reviewed. In 20 cases the infection presented in advanced stages of the disease when the patient fulfilled AIDS criteria. The most frequent foci in both community acquired and nosocomial infection was respiratory (16 and 3 cases, respectively). Fifty percent of the cases presented bacteremia. The classically described predisposing factors for infection by this germ were presented in 19 patients. Pseudomonas aeruginosa was the most frequently isolated type (22 cases). Only 5 patients received the appropriate treatment on admission. Clinical cure was achieved in 23 patients, with recurrence being observed in 10. Five patients died in relation to the infection. CONCLUSIONS: Infections by Pseudomonas spp. in Spain appear to have increased in frequency in patients with HIV infection in the last decade. These infections appear in advanced phases of the disease and mainly involve the lung, with high rates of bacteremia and a high number of recurrence. Empiric treatment of patients with advanced HIV infection with suspicion of bacterial infection should include antipseudomonic drugs.

Adult↗
PubMed1996

[Fever of unknown origin in patients with HIV infection].

BACKGROUND: The aim of the study was to describe the etiology and clinical characteristics of fever of uncertain origin (FUO) among HIV-infected patients. METHODS: Prospective analysis of 35 episodes of FUO in HIV-infected patients from Balearic Islands that were studied through established guidelines. RESULTS: Most patients were at advanced stages of HIV-1 infection (mean CD4 cell count, 60/mm3). Mean duration of fever until diagnosis was 57 days. Average time of hospitalization until etiological diagnosis of FUO was 26 days (range: 8-127 days). The cause of FUO was identified in 33 cases (94%). Tuberculosis accounted for 18 cases (51%) and visceral leishmaniasis for 8 cases (23%). Other opportunistic infections were the cause of FUO in 8 cases (17%). In one patient, fever was due to Kaposi's sarcoma. Two patients died while febrile, without and identified etiology. Four patients had more than one cause that could contribute to FUO. Imaging techniques that yielded more diagnostic information were abdominal ultrasonography and serial chest X-ray. Leishmania serology and tuberculin skin test showed a high specificity but low sensitivities. Invasive procedures with a highest diagnostic field were fine needle aspirate of lymph nodes, and liver biopsy. CONCLUSIONS: FUO is more frequent in advanced stages of HIV disease. In our area, FUO is caused primarily by endemic opportunistic infections specially TB and visceral leishmaniasis, and rarely can be attributable to HIV or neoplastic diseases.

AIDS-Related Opportunistic Infections↗
PubMed1995

[Changes in the natural history of AIDS in patients from Mallorca and Ibiza: 1986-1992].

BACKGROUND: Longitudinal follow-up studies in patients with human immunodeficiency virus (HIV) infection and AIDS, which are fundamental for the knowledge of variations the natural history of this disease, have generally been carried out by Public Health Departments and in populations in which homosexual males predominate. The aim of the present study was to analyze the changes in the natural history of the patients diagnosed with AIDS in the islands of Mallorca and Ibiza. METHODS: A prospective study of the adult patients diagnosed with AIDS in Mallorca and Ibiza, from 1986 to 1992 was performed. RESULTS: The annual incidence of the cases of AIDS increased throughout the study. The mean age of the patients did not vary, and neither did that in relation to sexes. A progressive decrease was observed in CD4 lymphocytes at the time of diagnosis (from 0.168 x 10(9)/l in 1986 to 0.079 x 10(9)/l in 1992). There was an increase in heterosexual transmission patients with no known risk factors also increased over the period studied. The incidence of extrapulmonary tuberculosis decreased both as the form of presentation and in its global frequency. Pneumonia by Pneumocystis carinii increased mainly as a initial feature. The median survival was 547 days and did not vary significantly throughout the study. CONCLUSIONS: The epidemiologic and clinical study of AIDS in Mallorca and Ibiza, Spain is similar to that observed in other Mediterranean regions. The incidence of extrapulmonary tuberculosis has decreased.

AIDS-Related Opportunistic Infections↗
PubMed1995

Nitric oxide modulates pancreatic basal secretion and response to cerulein in the rat: effects in acute pancreatitis.

BACKGROUND/AIMS: Nitric oxide synthase activity is detected in the pancreas, but the role of NO on pancreatic function has not been fully characterized. The aim of this study was to evaluate the role of NO in normal and diseased pancreatic function. METHODS: Amylase and NO secretion were measured in vivo in rats and in vitro in dispersed acini, with and without NO synthesis blockade, by NG-nitro-L-arginine methyl ester (L-NAME). Rats were subjected to cerulein-induced pancreatitis, and the effects of L-NAME or NO donors were assessed. RESULTS: L-NAME reduced amylase output to 60% of basal. This effect was reversed by L-arginine. The secretory response to optimal doses of cerulein induced a poor amylase secretion and a marked release of NO. High doses of cerulein in combination with L-NAME inhibited NO formation and amylase secretion. In dispersed acini, supramaximal cerulein concentrations induced NO release, but the amylase dose-response curve was not modified by NO inhibition. In acute pancreatitis, L-NAME increased amylasemia and tissue myeloperoxidase activities, whereas NO donors reduced amylasemia, lipasemia, and the histological damage score. CONCLUSIONS: The L-arginine/NO pathway facilitates basal and stimulated pancreatic secretion in vivo. NO donor drugs may improve the course of acute pancreatitis.

Acute Disease↗
PubMed1995

Induction of nitric oxide synthase in colonic smooth muscle from patients with toxic megacolon.

BACKGROUND & AIMS: Colonic inflammation may lead to motility disturbances, including severe atony. Nitric oxide is released by inflamed tissue and induces smooth muscle relaxation. The aim of this study was to analyze NO generation pathways in colonic tissue from patients who had ulcerative colitis with or without toxic megacolon and in tumor-free samples from patients with colonic neoplasm. METHODS: Enzymatic activity was determined by transformation of [14C]arginine to [14C]citrulline in mucosa and muscular layer samples. Immunostaining of tissue sections with antibody against inducible NO synthase was investigated. The effects of endotoxin on NO synthase activity was tested in muscle strips from human colon. RESULTS: Ca(2+)-independent NO synthase was undetectable or very low in muscularis propria from tumor and colitis controls. In contrast, specimens from patients with toxic megacolon had high activity (P < 0.05). Positive immunostaining for inducible NO synthase was found in muscular layers from patients with megacolon but not in tumor and colitis controls. Finally, endotoxin induced Ca(2+)-independent NO synthase activity in colonic muscle. CONCLUSIONS: Toxic megacolon is associated with the appearance of inducible NO synthase in the colonic muscularis propria. Local generation of excessive amounts of NO may be responsible for the colonic dilatation that is the hallmark of this syndrome.

Adult↗
PubMed1995

Induction of chronic cholangitis in the rat by trinitrobenzenesulfonic acid.

We investigated the effects of the hapten trinitrobenzenesulfonic acid instilled into the rat biliary tree. The study included three groups of animals that received a single intracholedochal injection of either saline, 10% ethanol or 10 mg trinitrobenzenesulfonic acid dissolved in 10% ethanol. A fourth group of rats was subjected to common bile duct ligation and was used as control for biliary obstruction. Liver and biliary tract dysfunction was assessed 1, 10, 20 and 30 days after treatment by serum aspartate aminotransferase, alkaline phosphatase and bilirubin, and by histopathological examination of liver slices. By day 10, saline- or ethanol-treated rats did not show changes in the biochemical parameters, and light microscopy revealed no alterations. In contrast, rats treated with trinitrobenzenesulfonic acid showed significant increases in all serum markers throughout the study period. Inflammatory cell infiltrates were seen in portal areas and around bile ducts, indicating pericholangitis. Some rats presented with dilatation of extrahepatic biliary ducts; ductal proliferation and thin porto-portal fibrotic septa were observed in these cases. Bile duct ligation also induced ductal proliferation and fibrosis in all cases, but pericholangitis was not prominent. Retrograde cholangiograms in trinitrobenzenesulfonic acid rats showed distortion of the intra- and extrahepatic biliary tree. In conclusion, chronic cholangitis may be consistently induced in rats by a single intracholedochal administration of trinitrobenzenesulfonic acid.

Alkaline Phosphatase↗
PubMed1995

Does Helicobacter pylori infection increase gastric sensitivity in functional dyspepsia?

The role of Helicobacter pylori infection in the pathogenesis of functional dyspepsia is debated. It is known that a substantial fraction of dyspeptic patients manifest a low discomfort threshold to gastric distension. This study investigated the symptomatic pattern in 27 H pylori positive and 23 H pylori negative patients with chronic functional dyspepsia, and potential relations between infection and gastric hyperalgesia. Specific symptoms (pain, nausea, vomiting, bloating/fullness, early satiety) were scored from 0 to 3 for severity and frequency (global symptom scores: 0-15). The mechanical and perceptive responses to gastric accommodation were evaluated with an electronic barostat that produced graded isobaric distensions from 0 to 20 mm Hg in 2 mm Hg steps up to 600 ml. Gastric compliance (volume/pressure relation) and perception (rating scale: 0-10) were quantified. Standard gastrointestinal manometry and recorded phasic pressure activity at eight separate sites during fasting and postprandially were also assessed. H pylori positive and H pylori negative patients manifested similar severity and frequency of specific symptoms and global symptom scores (mean (SEM)) (severity: 9.5 (2.0) v 9.0 (2.1); frequency: 10.8 (2.0) v 9.7 (2.2)). No differences were seen either in gastric compliance (53 (4) ml/mm Hg v 43 (3) ml/mm Hg) or in gastric perception of distension (slope: 0.50 (0.05) v 0.53 (0.06)). Postprandial antral motility was significantly decreased in H pylori positive patients (two hours motility index: 10.4 (0.6) v 12.6 (0.5); p < 0.05). It is concluded that H pylori infected patients with functional dyspepsia present no distinctive symptoms by comparison with H pylori negative counterparts and H pylori infection is associated with diminished postprandial antral motility but it does not increase perception of gastric distension.

Adolescent↗