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Biomedical subjects

A A Laudanna

Publications and source records attributed to A A Laudanna.

At least 19 recordsLinked to original sources
PubMed2004

Effect of a selective nonsteroidal anti-inflammatory inhibitor of cyclooxygenase-2 on the small bowel of rats.

The pathogenesis of nonsteroidal anti-inflammatory drug (NSAID) enteropathy is a complex process involving the uncoupling of mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase (COX). Rofecoxib, a selective inhibitor of COX-2, has shown less gastric damage, but the same beneficial effect is not clear in the case of the small bowel. Fifty-seven male Wistar rats (250-350 g) were divided into three groups (N=19 each) to evaluate the effect of this NSAID on the rat intestine. The groups received 2.5 mg/kg rofecoxib, 7.5 mg/kg indomethacin or water with 5% DMSO (control) given as a single dose by gavage 24 h before the beginning of the experiment. A macroscopic score was used to quantify intestinal lesions and intestinal permeability was measured using [51Cr]-ethylenediaminetetraacetic acid ([51Cr]-EDTA). The extent of intestinal lesion, indicated by a macroscopic score, was significantly lower when rofecoxib was administered compared to indomethacin (rofecoxib=0.0 vs indomethacin=63.6 +/- 25.9; P<0.05) and did not differ from control. The intestinal permeability to [51Cr]-EDTA was significantly increased after indomethacin (control=1.82 +/- 0.4 vs indomethacin=9.12 +/- 0.8%; P<0.0001), but not after rofecoxib, whose effect did not differ significantly from control (control=1.82 +/- 0.4 vs rofecoxib=2.17 +/- 0.4%; ns), but was significantly different from indomethacin (indomethacin=9.12 +/- 0.8 vs rofecoxib=2.17 +/- 0.4%; P<0.001). In conclusion, the present data show that rofecoxib is safer than indomethacin in rats because it does not induce macroscopic intestinal damage or increased intestinal permeability.

Animals↗
PubMed2003

Lack of evidence for the pathogenic role of iron and HFE gene mutations in Brazilian patients with nonalcoholic steatohepatitis.

The hypothesis of the role of iron overload associated with HFE gene mutations in the pathogenesis of nonalcoholic steatohepatitis (NASH) has been raised in recent years. In the present study, biochemical and histopathological evidence of iron overload and HFE mutations was investigated in NASH patients. Thirty-two NASH patients, 19 females (59%), average 49.2 years, 72% Caucasians, 12% Mulattoes and 12% Asians, were submitted to serum aminotransferase and iron profile determinations. Liver biopsies were analyzed for necroinflammatory activity, architectural damage and iron deposition. In 31 of the patients, C282Y and H63D mutations were tested by PCR-RFLP. Alanine aminotransferase levels were increased in 30 patients, 2.42 1.12 times the upper normal limit on average. Serum iron concentration, transferrin saturation and ferritin averages were 99.4 31.3 g/dl, 33.1 12.7% and 219.8 163.8 g/dl, respectively, corresponding to normal values in 93.5, 68.7 and 78.1% of the patients. Hepatic siderosis was observed in three patients and was not associated with architectural damage (P = 0.53) or with necroinflammatory activity (P = 0.27). The allelic frequencies (N = 31) found were 1.6 and 14.1% for C282Y and H63D, respectively, which were compatible with those described for the local population. In conclusion, no evidence of an association of hepatic iron overload and HFE mutations with NASH was found. Brazilian NASH patients comprise a heterogeneous group with many associated conditions such as hyperinsulinism, environmental hepatotoxin exposure and drugs, but not hepatic iron overload, and their disease susceptibility could be related to genetic and environmental features other than HFE mutations.

Adult↗
PubMed2003

Reduction of abdominal pressure in patients with ascites reduces gastroesophageal reflux.

The effect of the reduction of intra-abdominal pressure on the lower esophageal sphincter pressure (LESP) and the 24-hour pH monitoring were studied in 16 patients with ascites before and after paracentesis. LESP did not change (P > 0.05) with the reduction of intra-abdominal pressure (before paracentesis: 17.48 mmHg and postparacentesis: 18.67 mmHg). The results were divided into two groups according to the achieved reduction in intra-abdominal pressure group A were those in who the reduction was greater than 70% and B consisted of those a reduction of less than 70%. LESP did not change even when results for each group were considered separately (P > 0.05): group A (before: 15.60 mmHg; after: 18.09 mmHg); group B (before: 23.09 mmHg; after: 20.40 mmHg). However the 24-h pH monitoring showed pathological reflux in patients with ascites that was reduced with the paracentesis (P < 0.05; total number of reflux episodes before paracentesis was 520.26, and after, 136.26). All pH-monitoring parameters were statistically different (P < 0.05) before and after the reduction of intra-abdominal pressure for group A but not for group B. LESP does not change significantly (P > 0.05) when the intra-abdominal pressure is significantly reduced (P < 0.05). Patients with ascites showed gastroesophageal reflux. Intra-abdominal pressure reduction greater than 70% lead to a significant reduction in gastroesophageal reflux.

Abdomen↗
PubMed2002

Analysis of HLA-A antigens and C282Y and H63D mutations of the HFE gene in Brazilian patients with hemochromatosis.

The hemochromatosis gene, HFE, is located on chromosome 6 in close proximity to the HLA-A locus. Most Caucasian patients with hereditary hemochromatosis (HH) are homozygous for HLA-A3 and for the C282Y mutation of the HFE gene, while a minority are compound heterozygotes for C282Y and H63D. The prevalence of these mutations in non-Caucasian patients with HH is lower than expected. The objective of the present study was to evaluate the frequencies of HLA-A antigens and the C282Y and H63D mutations of the HFE gene in Brazilian patients with HH and to compare clinical and laboratory profiles of C282Y-positive and -negative patients with HH. The frequencies of HLA-A and C282Y and H63D mutations were determined by PCR-based methods in 15 male patients (median age 44 (20-72) years) with HH. Eight patients (53%) were homozygous and one (7%) was heterozygous for the C282Y mutation. None had compound heterozygosity for C282Y and H63D mutations. All but three C282Y homozygotes were positive for HLA-A3 and three other patients without C282Y were shown to be either heterozygous (N = 2) or homozygous (N = 1) for HLA-A3. Patients homozygous for the C282Y mutation had higher ferritin levels and lower age at onset, but the difference was not significant. The presence of C282Y homozygosity in roughly half of the Brazilian patients with HH, together with the findings of HLA-A homozygosity in C282Y-negative subjects, suggest that other mutations in the HFE gene or in other genes involved in iron homeostasis might also be linked to HH in Brazil.

Adult↗
PubMed2001

Thermolabile and calcium-dependent serum factor interferes with polymerized actin, and impairs anti-actin antibody detection.

The detection of anti-actin (AAA) by immunofluorescence is hindered by the presence of a serum factor. To better understand how it interferes with AAA detection, we tested sera from 20 patients with autoimmune hepatitis, and from 21 healthy adults, diluted 1:10 and prepared as follows: (A) diluted with PBS; (B) inactivated at 56 degrees C, and diluted with PBS; (C) diluted with 34 mM EDTA/PBS; (D) heated and diluted with EDTA/PBS. To reveal AAA, a fluorescein-labelled anti-human IgG was used in the process of indirect immunofluorescence. In a parallel assay, the substrate, acetone-fixed human fibroblasts, was preincubated with sera prepared as if it were to identify AAA, but instead, a rhodamine-phalloidin was used to identify F-actin, by direct immunofluorescence. All sera from patients were reactive to AAA when heat-inactivated and/or calcium-chelated, and 60% of them when diluted with unmodified sera (P=0.004). F-actin continued to be present after preincubation with heat-inactivated or calcium-chelated sera from patients and healthy controls, and in 41.5% of reactions with unmodified serum (P=0.0000001). The heat inactivation and the calcium chelation were both efficient procedures for maintaining the microfilament structure intact after serum incubation and, therefore, for identifying AAA.

Actin Depolymerizing Factors↗
PubMed2001

Autoimmune hepatitis in Brazilian patients is not linked to tumor necrosis factor alpha polymorphisms at position -308.

BACKGROUND/AIMS: Susceptibility to autoimmune hepatitis (AIH) has been linked to different HLA-DR antigens. Recently, AIH type 1 was associated with polymorphisms in the tumor necrosis factor alpha gene promoter (TNFA) at position -308. In this respect, the frequency of the TNFA*2 allele, in linkage disequilibrium with HLA-DRB1*0301, was shown to be significantly increased in whites with AIH type 1. The aim of this study was to assess the role of TNFA alleles in conferring susceptibility to AIH, studying a population where the disease is not primarily associated with HLA-DRB1*03. METHODS: The determination of HLA-DRB1 and TNFA alleles was performed in 92 patients with AIH type 1, 29 subjects with AIH type 2 and 83 healthy controls by polymerase chain reaction-based techniques. RESULTS: The distribution of TNFA alleles was similar in patients with AIH types 1 and 2, when compared with controls. In addition, the TNFA*2 allele was identified in patients carrying HLA-DR antigens other than HLA-DRB1*03. Interestingly, higher gammaglobulin levels were observed in TNFA*2 positive patients. CONCLUSIONS: Our data indicate that susceptibility to AIH remains primarily linked to the HLA-DRB1 locus, and suggest that the association of AIH with TNFA*2 previously observed in whites might be secondary to a linkage disequilibrium with HLA-DRB1*0301.

Adolescent↗
PubMed2001

Protective effect of metronidazole on uncoupling mitochondrial oxidative phosphorylation induced by NSAID: a new mechanism.

BACKGROUND: The pathogenesis of non-steroidal anti-inflammatory drug (NSAID) enteropathy is complex. It involves uncoupling of mitochondrial oxidative phosphorylation which alters the intercellular junction and increases intestinal permeability with consequent intestinal damage. Metronidazole diminishes the inflammation induced by indomethacin but the mechanisms remain speculative. A direct effect on luminal bacteria has traditionally been thought to account for the protective effect of metronidazole. However, a protective effect of metronidazole on mitochondrial oxidative phosphorylation has never been tested. AIMS: To assess the protective effect of metronidazole on mitochondrial uncoupling induced by indomethacin and also on the increased intestinal permeability and macroscopic damage. MATERIAL AND METHODS: The protective effect of metronidazole was evaluated in rats given indomethacin; a macroscopic score was devised to quantify intestinal lesions, and intestinal permeability was measured by means of (51)Cr-ethylenediaminetetraacetic acid. The protective effect of metronidazole against mitochondrial uncoupling induced by indomethacin was assessed using isolated coupled rat liver mitochondria obtained from rats pretreated with metronidazole or saline. RESULTS: Metronidazole significantly reduced the macroscopic intestinal damage and increase in intestinal permeability induced by indomethacin; furthermore, at the mitochondrial level, it significantly reduced the increase in oxygen consumption in state 4 induced by indomethacin and caused less reduction of the respiratory control rate. CONCLUSION: Our study confirmed the beneficial effects of metronidazole on intestinal damage and intestinal permeability, and demonstrated, for the first time, a direct protective effect of metronidazole on uncoupling of mitochondrial oxidative phosphorylation caused by NSAIDs.

Animals↗
PubMed2001

Intestinal permeability in strongyloidiasis.

The objective of the present study was to assess intestinal permeability in patients with infection caused by Strongyloides stercoralis. Twenty-six patients (16 women and 10 men), mean age 45.9, with a diagnosis of strongyloidiasis were evaluated. For comparison, 25 healthy volunteers (18 women and 7 men), mean age 44.9, without digestive disorders or intestinal parasites served as normal controls. Intestinal permeability was measured on the basis of urinary radioactivity levels during the 24 h following oral administration of chromium-labeled ethylenediaminetetraacetic acid ((51)Cr-EDTA) expressed as percentage of the ingested dose. The urinary excretion of (51)Cr-EDTA was significantly reduced in patients with strongyloidiasis compared to controls (1.60 +/- 0.74 and 3.10 +/- 1.40, respectively, P = 0.0001). Intestinal permeability is diminished in strongyloidiasis. Abnormalities in mucus secretion and intestinal motility and loss of macromolecules could explain the impaired intestinal permeability.

Adult↗
PubMed2000

Involvement of the pancreas in AIDS: a prospective study of 109 post-mortems.

BACKGROUND: Pancreatic involvement in AIDS is rarely mentioned in medical literature. AIMS: To identify the main morphological patterns of the pancreas using optical and electron microscopy in AIDS patients. DESIGN: An open, prospective, and sequential study in a tertiary institutional hospital. METHODS: Consecutive post-mortems of 109 AIDS patients and 38 controls (1995). Baseline characteristics of AIDS patients and controls were evaluated. Morphological analysis consisted of: (i) semi-quantitative score of acinar and parenchymal elements; (ii) qualitative analysis of ducts, vascular components, nerves, and Langerhans' islets; (iii) specific stains and immunohistochemistry for opportunistic agents; (iv) ultrastructural data. RESULTS: The mean age of AIDS patients was 37 years; 80% were male; 60% were white; 21% were alcoholic. All patients with AIDS had normal blood amylase, blood glucose, and pancreatic ultrasound. Histological findings were: acinar atrophy (60%), few zymogen granula in acinar cytoplasm (52%), abnormalities in acinar nucleus (65%), pancreatic steatosis (66%), and focal necrosis (17%). Immunohistochemistry revealed: mycobacteriosis (22%), toxoplasmosis (13%), cytomegalovirus (9%), Pneumocystis carinii (9%), and HIV p24 antigen in macrophage cytoplasm (22%). Ultrastructural examination showed: decreased zymogen granula, enlargement and proliferation of the endoplasmic reticulum and mitochondria, nuclear abnormalities, and increased lipid droplets in acinar cytoplasm. CONCLUSION: Pancreatic involvement in AIDS is very frequent (90%) and is usually asymptomatic. Morphological changes showed three patterns of pancreatic alterations: 'nutritional-like', inflammatory and both of these together. The 'nutritional-like' pattern (atrophy, few zymogen granula and steatosis) may be due to many factors such as nutritional characteristics (Kwashiorkor-like) induced by the HIV infection or related to the HIV virus itself.

AIDS-Related Opportunistic Infections↗
PubMed1999

Systemic hemodynamic changes in mansonic schistosomiasis with portal hypertension treated by azygoportal disconnection and splenectomy.

OBJECTIVE: The aim of this study was to assess systemic hemodynamic changes in patients with Manson's schistosomiasis and portal hypertension during azygoportal disconnection and splenectomy. METHODS: Sixteen patients with portal hypertension secondary to hepatosplenic schistosomiasis with indication for surgery were studied prospectively. All underwent invasive hemodynamic monitoring with pulmonary artery catheter. The first systemic hemodynamic assessment was performed preoperatively. In the intraoperative period new hemodynamic data were collected as follows: a) after laparotomy; b) 15-30 min after splenic artery ligature; c) 15-30 min after splenectomy; and d) after ligation of the collateral circulation. RESULTS: The results indicated preoperatively that the patients presented with an increased cardiac index (4.40 +/- 0.94 L/min/m2) together with a reduction in the systemic vascular resistance index (1692.25 +/- 434.91 dyne.s/cm5.m2). The stroke index (53.74 +/- 10.40 ml/beat/m2) and both left (5.71 +/- 1.50 kg.m/m2) and right heart work indexes (1.12 +/- 0.74 kg.m/m2) were also elevated. The mean pulmonary artery pressure was increased (17.81 +/- 9.00 mm Hg) and the pulmonary vascular resistance index decreased (164.31 +/- 138.69 dyne.s/cm5.m2). From the moment that the splenic artery was ligated until the end of the procedure, the cardiac index (3.45 +/- 0.90 L/min/m2) was reduced and the systemic vascular resistance index (2059.50 +/- 590.05 dyne.s/cm5.m5) increased. The systolic index (44.25 +/- 11.01 ml/beat/m2) and the left ventricle work index (4.33 +/- 1.29 kg.m/m2) also reduced. The mean pulmonary artery pressure (19.18 +/- 9.21 mm Hg) and the right ventricle work index (0.94 +/- 0.62 mm Hg) remained elevated after the surgical procedure. CONCLUSIONS: The data allowed us to conclude that hepatosplenic schistosomiasis induces a hyperdynamic circulatory state that was corrected after splenectomy and azygoportal disconnection, remaining a mild pulmonary hypertension. Therefore, these changes are correlated with the portosystemic collateral circulation, especially as a consequence of splanchnic hyperflow.

Adolescent↗
PubMed1999

Genetic heterogeneity in susceptibility to autoimmune hepatitis types 1 and 2.

OBJECTIVE: Susceptibility to autoimmune hepatitis (AIH) type 1 has been associated with DRB1*03, DRB1*04, and DRB3 alleles in European and North-American whites, with DRB1*04 in Japan, and with DRB1*04 and DRB1*13 in Latin America. Very few studies have been performed on AIH type 2. The aim of the present study was to evaluate the association of AIH types 1 and 2 with HLA-DR and DQ loci. METHODS: We performed HLA-DRB and -DQB1 typing by polymerase chain reaction amplification with sequence-specific primers (PCR-SSP) in 139 AIH patients. Most had AIH type 1 associated with circulating anti-smooth muscle antibody with F-actin specificity or antinuclear antibody. Twenty-eight patients presented AIH type 2 with anti-liver/kidney microsome type 1 or anti-liver cytosol type 1 antibodies. RESULTS: We observed a significant increase of DRB1*13 (70% vs 26% of controls, p < 0.00001) and DRB3 (93% vs 69% of controls, p < 0.00001) in AIH type 1 patients. Analysis of patients without DRB1*13 disclosed a secondary association with DRB1*03 (70% vs 30% of controls, p = 0.0001) and either the DRB1*13 or the DRB1*03 alleles were present in the majority of these patients (91% vs 48% of controls, p = 0.001). Comparison of DRB1*13- and DRB1*03-positive subjects revealed that the former alleles conferred susceptibility to younger patients with AIH type 1. DQB1 typing showed a significant increase in DQB1*06 (68% vs 41% of controls, p = 0.00007) in strong linkage disequilibrium with DRB1*13, and a decrease in DQB1*0301 (8% vs 47% of controls, p(c) = 0.0003). On the other hand, HLA typing of patients with AIH type 2 disclosed a significant increase in the DRB1*07 (68% vs 20% of controls, p(c) < 0.00014), DRB4 (79% vs 43% of controls, p(c) = 0.004), and DQB1*02 (86% vs 42%, p = 0.00002) alleles. After exclusion of DRB1*07, a secondary association with HLA-DRB1*03 was further observed in these patients (78% vs 30%, p = 0.007) and most of them had either DRB1*07 or DRB1*03 (93% vs 44% of controls, p(c) < 0.0001). CONCLUSIONS: Our data indicate that predisposition to AIH types 1 and 2 is associated, respectively, with the DRB1*13 or DRB1*03 and DRB1*07 or DRB1*03 alleles, and suggest that protection against type 1 disease may be conferred by DQB1*0301. In addition, the cluster of DRB1*13 in children with AIH type 1 also supports the concept that different HLA alleles might influence the onset of the disease.

Adolescent↗
PubMed1999

Infrequent p53 gene alterations in ulcerative colitis.

The purpose of this study was to determine whether point mutations and loss of the p53 gene take place in ulcerative colitis which is histologically negative for dysplasia. DNA was extracted from 13 frozen rectal or colon biopsies and blood samples. Ulcerative colitis was classified histologically as active (10 cases) and inactive (3 cases). Exons 5-8 were amplified by PCR, treated with exonuclease and shrimp alkaline phosphatase and sequenced by the dideoxy chain termination method with the Sequenase Version 2.0 DNA sequencing kit. PCR products of intron 6 and exon 4 were digested with MspI and AccII, respectively, for RFLP analysis. No p53 gene mutation was detected in these cases. The number of informative patients for loss of heterozygosity (LOH) at the p53 intron 6 was high, 11 out of 12 (92%), whereas no LOH was observed. LOH affecting p53 exon 4 was not detected in lesions from 5 of 12 patients (42%). In ulcerative colitis, tumor progression is similar to that in sporadic colon cancer, and other oncogenes and tumor suppressor genes are likely to be mutated before the p53 gene.

Adult↗
PubMed1999

Hansen's disease and the digestive system: clinical symptoms and gastric secretory profile at baseline conditions and following maximum stimulation with pentagastrin.

The incidence of digestive symptoms in 100 patients with Hansen's disease was evaluated in this study, following a standardized questionnaire. A correlation between the frequency of symptoms, the form of the disease, and the length of treatment was investigated. Digestive symptoms were found in 31 patients (31%). No statistically significant difference was found between the presence of symptoms and the length of the disease or between the multibacillary and the paucibacillary form of the disease. However, a positive correlation between digestive symptoms and Hansen's disease was found in the multibacillary form of the disease only for patients treated for more than 12 months. Baseline and pentagastrin-stimulated gastric acid secretion was studied in 30 Hansen's disease patients and in 10 controls. A Iower basal acid output was observed in patients with Hansen's disease, but no statistical difference was found. Pentagastrin-stimulated gastric acid secretion was statistically different in Hansen's disease patients, as compared to controls. A Iower pentagastrin-stimulated acid secretion was found in Hansen's disease patients under treatment, as compared to untreated patients, but the difference was not statistically significant.

Adolescent↗
PubMed1998

Unexpected clinical remission of cholestasis after rifampicin therapy in patients with normal or slightly increased levels of gamma-glutamyl transpeptidase.

OBJECTIVE: Rifampicin is an effective drug against pruritus in intrahepatic cholestasis. However, there is no specific hepatic disease in which its use could cause undoubtedly biochemical improvement. The aim of this study was to describe patients with complete remission of cholestatic symptoms after rifampicin therapy. METHODS: We reported three female patients with intrahepatic cholestasis with no evidence of viral, metabolic, or autoimmune liver diseases. Total bilirubin levels ranged from 13.2 to 27.2 mg/dl (before the first treatment with rifampicin), and in all of them gamma-glutamyl transpeptidase values were within the normal range or slightly increased. Rifampicin therapy was administered orally, without any concomitant drug, with an effective dosage of 5-17 mg/kg/day. RESULTS: In all patients, pruritus ceased completely and bilirubin returned to normal values. The symptoms recurred after rifampicin withdrawal on, at least, three occasions in each patient, and these symptoms were always eliminated after its reintroduction. The patients had a total of 16 cholestatic episodes during a follow-up of 8 yr, with a complete clinical recovery in all of them. Undergoing therapy with a suitable dosage of rifampicin, none of the patients had a cholestatic crisis even during a period for as long as 12 months. The diagnosis of two patients was consistent with benign recurrent intrahepatic cholestasis, and it was not well defined in the remaining. CONCLUSION: Rifampicin may induce clinical remission, and perhaps prevent clinical relapses of intrahepatic cholestasis with normal or slightly increased levels of gamma-glutamyl transpeptidase.

Adult↗
PubMed1998

Value of peritoneal lavage cytology during laparoscopic staging of patients with gastric carcinoma.

Forty-nine consecutive patients with advanced gastric carcinoma underwent preoperative staging by laparoscopy between June 1991 and June 1992. Peritoneal lavage with cytologic examination was performed when ascites was not present. In eight cases (16.3%), laparoscopy revealed carcinomatosis and/or multiple hepatic metastases, so laparotomy was not performed. Intraperitoneal free cancer cells (IFCCs) were detected in 41% of patients (65% in patients with ascites and 28% by peritoneal lavage). In the absence of macroscopic peritoneal dissemination, IFCCs were encountered in 29% of patients. IFCCs were present only when invasion of the gastric serosa was >3 cm2 or when adjacent organs and structures were already invaded. Mucinous adenocarcinoma, Borrmann class IV tumors, and Stage IV patients had higher incidence of IFCCs. Cytologic results were similar at laparoscopy and laparotomy (p > 0.05). Therefore, cytologic evaluation of peritoneal lavage added sensitivity to laparoscopy in assessing patients with advanced gastric carcinoma and may alter their therapeutic approach.

Adenocarcinoma↗
PubMed1997

Effects of colectomy on gallbladder motility in patients with ulcerative colitis.

In order to gain insight into the possible mechanisms involved in gallstone formation in colectomized ulcerative colitis patients, we studied gallbladder motility by means of ultrasonography in three groups of subjects: controls (N = 40) and ulcerative colitis patients without (N = 30) and with (N = 20) colectomy. Impaired gallbladder emptying after a liquid fatty meal stimulus was observed in ulcerative colitis patients with colectomy compared with those obtained in ulcerative colitis patients without colectomy and controls (P = 0.001). The maximum percentage of gallbladder emptying also, was significantly lower (59.8%) than those seen in ulcerative colitis patients without colectomy (74.5%) and controls (77.8%) (P = 0.001). Diminished gallbladder emptying with ensuing stasis might be a contributory factor to the increased prevalence of gallstones in colectomized patients.

Adult↗