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Biomedical subjects

A Giménez

Publications and source records attributed to A Giménez.

At least 19 recordsLinked to original sources
PubMed2001

Anti-Trypanosoma activity of some natural stilbenoids and synthetic related heterocyclic compounds.

We report the anti-Chagasic activity of the natural dihydrostilbenoid isonotholaenic acid and several simple derivatives, as well as that of some representative compounds of related synthetic series, with basic structures of benzalphthalides, dihydrostilbamides, isoindoles, phthalazin-1-ones, imidazo[2,1-a]isoindoles and pyrimido[2,1-a]isoindoles. The evaluation was performed in vitro on cultures of epimastigote and trypomastigote forms of Trypanosoma cruzi. Some of the tested compounds resulted to be as potent as benznidazole (epimastigotes), and others were shown to be more active than gentian violet (trypomastigotes), used as reference drugs.

Animals↗
PubMed2001

Blood sulfur-amino acid concentration reflects an impairment of liver transsulfuration pathway in patients with acute abdominal inflammatory processes.

Whole-blood free amino acids were measured in a control group made up of eight healthy women fasted for 12 h and also in eight patients with acute pancreatitis, five patients with acute cholecystitis and seven patients with acute appendicitis. Blood was withdrawn immediately on admission to hospital and again 3 d later following a controlled peripheral parenteral nutrition diet; this is with the exception of the appendicitis group. l-Cystathionine and l-methionine concentrations were significantly higher in pancreatitis and appendicitis patients when compared with controls. In the pancreatitis and cholecystitis patients, l-serine concentration was also significantly higher when compared with controls. The l-homocysteine concentration was significantly higher only in the appendicitis group when compared with the control group. l-Cystine concentration was unchanged in all the patients studied when compared with control subjects. The l-methionine : l-cystine ratio was significantly higher and the l-glutamine : l-cystine ratio was significantly lower in all the patients when compared with controls. The blood S-amino acid pattern reflects an impairment in liver transsulfuration pathway during acute abdominal processes. This work supports the idea that the l-methionine : l-cystine and l-glutamine : l-cystine ratios can be taken as good markers to evaluate the S-amino acid metabolism and suggests the importance of using N-acetylcysteine as a required nutrient in these situations.

Acetylcysteine↗
PubMed2000

Enhanced DNA binding and activation of transcription factors NF-kappa B and AP-1 by acetaldehyde in HEPG2 cells.

Because transcription factors NF-kappaB and activator protein-1 (AP-1) are known to regulate gene expression, we have analyzed the role of acetaldehyde in the activation of NF-kappaB and AP-1 in HepG2 cells. Binding activity and transactivation of NF-kappaB and AP-1 were determined by gel retardation assays and transfection of a luciferase reporter construct controlled by kappaB and AP-1 binding sites, respectively. Acetaldehyde enhanced the DNA binding of NF-kappaB and AP-1 by 1 and 4 h, respectively, increasing the kappaB- and AP-1-dependent luciferase expression. Supershift assays revealed the presence of NF-kappaB heterodimers p65/p50 and p50/p52, whereas nuclear c-Jun levels correlated with the DNA binding of AP-1. The enhanced binding of NF-kappaB to DNA by acetaldehyde in intact cells was accompanied by the proteolytic degradation of IkappaB-alpha. However, the addition of acetaldehyde to cytostolic extracts from untreated Hep G2 cells did not affect the DNA binding of AP-1 but activated the NF-kappaB heterodimer p65/p50 in the absence of IkappaB-alpha degradation. Preincubation of HepG2 cells with protein kinase C inhibitors abolished the enhanced DNA binding of NF-kappaB and AP-1 caused by acetaldehyde. Hence, these findings uncover a previously unrecognized role for acetaldehyde in the activation of NF-kappaB and AP-1, which may be of relevance in the alcohol-induced liver disease.

Acetaldehyde↗
PubMed2000

DNA ploidy status and proliferative activity as markers of malignant potential in Barrett's esophagus: flow cytometric study using routinely paraffin-embedded tissue.

Regular endoscopic surveillance is recommended for patients with Barrett's esophagus to detect dysplasia and to diagnose carcinoma while it is in an early and possibly treatable stage. However, there are numerous unknown aspects regarding the natural history of dysplasia in this disease, and there is still a need for more accurate markers of risk of a malignant change. The aim of this study was to investigate the usefulness of DNA flow cytometry in Barrett's esophagus to define subgroups of patients showing similar histologic findings but with a different malignancy potential. Routinely formalin-fixed and paraffin-embedded tissues of 43 patients with Barrett's esophagus were processed for flow cytometric measurements (ploidy, proliferative index) and the results were compared with the histologic evolution observed in these patients. Only in the group of patients with "indefinite" dysplasia did we find statistically significant differences between the samples from patients with and without progression to more severe lesions (mean proliferative index of stable patients: 5.2% versus 8.3% in patients with progression, p = 0.001, Student's t-test). The presence in the flow cytometric analysis of a DNA aneuploid cell line is closely related to the presence of severe histologic alterations (i.e., high-grade dysplasia: p < 0.001, Fisher's exact test). Our results suggest that this procedure is at least capable of distinguishing between a real, although incipient, neoplastic process and morphologic changes of a reactive or reparative type. The increment in the tissue proliferative index could be an indicator of an early genomic instability which, with time, will develop into lesions with a more altered DNA content: aneuploidy.

Adenocarcinoma↗
PubMed2000

Spontaneous pneumothorax and pneumomediastinum in IPF.

Patients with idiopathic pulmonary fibrosis (IPF) are at risk for a variety of acute pulmonary complications, including pneumothorax and pneumomediastinum. Our aim was to describe the radiographic and CT findings and to determine the frequency of complicating spontaneous pneumothorax and pneumomediastinum in patients with IPF. A retrospective study was performed including 78 consecutive patients who underwent CT scanning of the chest and who had confirmed IPF. The chest radiographs and CT scans were reviewed by two chest radiologists and classified as showing features of extra-alveolar air collections. The CT scans showed extra-alveolar air in 9 (11.2 %) of 78 patients (six females and three males; age range 26-90 years, mean age 65 years). Pneumothorax was demonstrated in 5 patients and mediastinal air collections in 4 patients. All patients had dyspnea for 1-48 months (mean 14 months). Of the five cases with pneumothorax, four developed acute onset of dyspnea and pleuritic chest pain, whereas 1 patient had a relatively stable functional status. Of the 4 patients with pneumomediastinum, three presented with nonpleuritic chest pain and acute dyspnea. Chest radiographs showed extra-alveolar air in 6 patients. Three cases were predicted to be negative by chest radiographs. Follow-up CT showed that air collections had resolved completely in 5 patients. Two patients died of respiratory failure within 4 months after CT. Extra-alveolar air should be recognized as a relatively common IPF-related complication. Chest CT is a useful imaging method in determining air collections in patients with IPF that become acutely breathless and their chest radiograph fails to reveal the presence of extra-alveolar air.

Adult↗
PubMed2000

Spontaneous reversibility of "pleural thickening" in a patient with semi-invasive pulmonary aspergillosis: radiographic and CT findings.

We present serial radiographic and CT findings of spontaneous reversibility of "pleural thickening" in a patient with proved semi-invasive pulmonary aspergillosis who developed bilateral intracavitary aspergillomas. To the best of our knowledge, this is the first report in the literature of this feature. Radiologists should be aware that pleural thickening in patients with semi-invasive aspergillosis does not necessarily indicate irreversible pleural fibrosis.

Aged↗
PubMed2000

Semiinvasive pulmonary aspergillosis in chronic obstructive pulmonary disease: radiologic and pathologic findings in nine patients.

OBJECTIVE: The purpose of this study is to assess the radiographic, thin-section CT, and histologic findings of semiinvasive aspergillosis in patients with chronic obstructive pulmonary disease (COPD). MATERIALS AND METHODS: The study included nine patients with COPD seen at the Hospital de Sant Pau during a 3-year period who had histopathologically proven aspergillosis with tissue invasion. Chest radiography and thin-section (2-mm collimation) CT of the chest were available in all cases. RESULTS: Nine patients had semiinvasive aspergillosis proven at autopsy (n = 7) or by thoracoscopically guided lung biopsy (n = 2). The radiologic findings consisted of parenchymal consolidation (n = 6) and nodules larger than 1 cm in diameter (n = 3). Parenchymal consolidation involved the upper lobes in five patients and was bilateral in four. Cavitation was present in two of the patients with consolidation and in two of the patients with nodular opacities. Adjacent pleural thickening was revealed by CT in four patients. Histologically, the areas of consolidation represented active inflammation and intraalveolar hemorrhage containing Aspergillus organisms. In the three patients with multiple cavitated nodules, a variable degree of central necrosis was observed. The inflammatory infiltrate extended into the surrounding lung parenchyma, and adjacent areas of hemorrhage were also seen. Aspergillus colonies were identified within the lung tissue. CONCLUSION: Upper lobe consolidation or multiple nodules in patients with COPD should raise the possibility of semiinvasive aspergillosis.

Aged↗
PubMed2000

S-adenosylmethionine prevents hepatic tocopherol depletion in carbon tetrachloride-injured rats.

In various experimental models, S-adenosylmethionine (SAMe) has been shown to reduce liver injury by preventing depletion of glutathione, one of the antioxidant systems that plays a critical role in defence against oxidative stress. On the other hand, alpha-tocopherol may be decreased in liver diseases, and treatment with this vitamin reduces liver injury in CCl(4)-treated rats. Since there is a close relationship among the different antioxidant systems (mainly glutathione, alpha-tocopherol and ascorbic acid), we have assessed whether, as well as restoring hepatic glutathione content, SAMe has any effect on liver alpha-tocopherol and ascorbic acid levels in CCl(4)-injured rats. Four groups of seven male Wistar rats treated for 9 weeks were studied: rats induced to cirrhosis with CCl(4), rats induced to cirrhosis plus SAMe administration (10 mg x kg(-1) x day(-1)) and their respective controls. Liver samples were obtained for measuring levels of glutathione, alpha-tocopherol, ascorbic acid and thiobarbituric acid-reactive substances (TBARS), and hydroxyproline concentration as an index of collagen content. The hydroxyproline content was higher in CCl(4)-injured rats than in the control group (4.4+/-1.8 and 1.1+/-0.3 micromol/g respectively; P<0.05). In CCl(4)-injured rats, SAMe administration decreased collagen content (2.7+/-1.0 microl/g; P<0.05) and TBARS, and corrected glutathione depletion. alpha-Tocopherol was significantly lower in CCl(4)-injured rats than in controls (17.3+/-4.9 and 23.0+/-4.0 micromol/g respectively; P<0.05). By contrast, alpha-tocopherol levels were similar (23.8+/-5.1 micromol/g) in CCl(4)-injured rats receiving SAMe and in controls. In CCl(4)-injured rats, liver ascorbic acid was decreased in comparison with controls (4.9+/-1.8 and 8.2+/-1.0 micromol/g respectively; P<0.05), levels which were not replenished by SAMe (4.6+/-0.4 micromol/g). In conclusion, SAMe not only decreases fibrosis and protects against hepatic glutathione depletion, but has a further antioxidant effect of preventing alpha-tocopherol depletion in CCl(4)-injured rats.

Animals↗
PubMed1999

Synthesis and degradation of collagen in pancreatic fibrogenesis.

The mechanism of fibrogenesis in the pancreas is not well known. We analyzed the role of prolylhydroxylase and collagenase activities in the development of fibrosis in chronic alcoholic pancreatitis (CAP). Nineteen patients with CAP and 11 controls (organ donors) with normal pancreatic histology were included in the study. Pancreatic tissue was obtained from all subjects to measure (a) area of fibrosis (histomorphometric method); (b) prolylhydroxylase activity (PHase), which reflects the intracellular synthesis of collagen (Hutton's method); and (c) collagenase activity, which reflects the degradation of collagen (collagenase assay system, 3H). The percentage of the fibrosis area in relation to the total area of pancreatic tissue was significantly higher in CAP than in the control group (70.6+/-20.2% vs. 4.6+/-1.8%; p<0.001). Mean pancreatic PHase activity was also significantly higher in CAP than in the control group (775+/-258 cpm/mg protein/h vs. 405+/-151 cpm/mg protein/h; p<0.001). The collagenase activity was significantly lower in CAP than in the control group (8.7+/-3.5 cpm/cpm added/mg protein vs. 18.0+/-3.9 cpm/cpm added/mg protein; p<0.001). A significant correlation was observed between percentage fibrosis evaluated histomorphometrically and PHase activity in all patients (r = 0.72; p<0.001), and between PHase and collagenase activities in controls (r = 0.70; p = 0.024), but not in CAP. Pancreatic tissue in CAP has an increased fibrogenic activity and an impaired collagen-degradation capacity. These findings might explain the excessive development of fibrosis in CAP.

Collagen↗
PubMed1999

Hepatic fibrogenic activity in chronic alcoholic pancreatitis.

The prevalence and the mechanisms of hepatic fibrosis in chronic alcoholic pancreatitis remain uncertain. The aim of this study was to investigate the fibrogenic activity of the liver in patients with chronic pancreatitis and its relation with either the alcohol or cholestasis. Liver biopsies were obtained from 16 patients with chronic pancreatitis at the time of surgery and from 10 organ donors. Samples were processed for histologic examination to assess the presence and extent of fibrosis, inflammatory reactions, and cholestasis- and alcohol-related lesions. In other samples, the collagen content was measured by morphometry, and prolylhydroxylase activity was determined. Liver-function tests, ultrasonography, and endoscopic retrograde cholangiopancreatography were performed before surgery in all the patients. Of patients with chronic pancreatitis, 75% had significantly greater hepatic fibrosis and prolylhydroxylase activity than the control group. Moreover, prolylhydroxylase activity in patients with chronic pancreatitis was higher in those with cholestasis or partial obstruction of the common bile duct than in those without cholestasis or partial obstruction of the common bile duct. Both the fibrogenic activity and the collagen content in the livers of patients with chronic alcoholic pancreatitis are significantly increased, even in those without histologic lesions, and these alterations may be secondary to a partial occlusion of the common bile duct.

Adolescent↗
PubMed1999

Immunohistochemical detection of p53 protein could improve the management of some patients with Barrett esophagus and mild histologic alterations.

OBJECTIVE: To determine the usefulness of p53 immunostaining in identifying the subgroup of patients with Barrett esophagus who may be at increased risk of developing adenocarcinoma of the esophagus. MATERIALS AND METHODS: Tissue samples of 41 patients with Barrett esophagus and available sequential histologic data were processed for p53 immunostaining. Results from each patient were compared over time, and the results of a subset of patients were compared with each other. RESULTS: We observed a significant correlation between the percentage of samples with p53 expression and the severity of dysplasia. Moreover, in a subset of patients with mild dysplasia (cases classified as showing indefinite dysplasia), we observed a statistically significant difference in the percentage of p53-positive samples between the group that progressed to more severe dysplasia and the group that did not progress. CONCLUSION: Our results suggest that this procedure, which is technically simple, economical, and quick, could play a role in the evaluation and follow-up of patients with Barrett esophagus.

Adenocarcinoma↗
PubMed1998

Flow cytometric DNA analysis and p53 protein expression show a good correlation with histologic findings in patients with Barrett's esophagus.

BACKGROUND: There is a considerable degree of subjectivity and, therefore, substantial interobserver and intraobserver disagreement in the diagnosis and grading of dysplastic lesions in Barrett's esophagus (BE). The aim of this study was to evaluate the usefulness of DNA flow cytometry and immunohistochemical staining for p53 protein as objective methods to complement the conventional histologic diagnosis of dysplasia in patients with this disease. The most common problems and the possible advantages of using these procedures are analyzed briefly in this article. METHODS: Formalin fixed, paraffin embedded tissue from 55 patients diagnosed with BE were processed for flow cytometric measurements (ploidy and proliferation index) and p53 immunostaining. RESULTS: Both the cytometric data and the positivity of staining for p53 revealed a statistically significant increase throughout the following sequence: no dysplasia --> indefinite for dysplasia --> low grade dysplasia --> high grade dysplasia --> adenocarcinoma. There was also a highly significant correlation between the results of the cytometric study and the positivity of staining for p53. CONCLUSIONS: In the future, the use of this procedure could play an important role in the evaluation of patients with BE. Considering that staining for p53 is technically simple, economical, and quick, and the materials required are available to most pathology laboratories, this method appears to be a firm candidate for application as a biomarker in BE. The authors have shown that it is possible to obtain adequate results for cytometric analysis with small formalin fixed, paraffin embedded biopsies if a strict protocol for the acceptance of tissue samples and/or histograms is observed.

Adenocarcinoma↗