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 percent 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 percent; 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 percent; ns), but was significantly different from indomethacin (indomethacin = 9.12 ± 0.8 vs rofecoxib = 2.17 ± 0.4 percent; 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.

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 percent), average 49.2 years, 72 percent Caucasians, 12 percent Mulattoes and 12 percent 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 + or - 1.12 times the upper normal limit on average. Serum iron concentration, transferrin saturation and ferritin averages were 99.4 + or - 31.3 g/dl, 33.1 + or - 12.7 percent and 219.8 + or - 163.8 æg/dl, respectively, corresponding to normal values in 93.5, 68.7 and 78.1 percent 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 percent 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

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 percent) were homozygous and one (7 percent) 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

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 (51Cr-EDTA) expressed as percentage of the ingested dose. The urinary excretion of 51Cr-EDTA was significantly reduced in patients with strongyloidiasis compared to controls (1.60 + or - 0.74 and 3.10 + or - 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

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 percent), whereas no LOH was observed. LOH affecting p53 exon 4 was not detected in lesions from 5 of 12 patients (42 percent). 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

Steroid receptors in Brazilian patients with large bowel cancer

1. Twenty-two colorectal carcinomas were examined for the presence of estrogen (ER), progesterone (PR), androgen (AR) and glucocorticoid receptors (GR) by a charcoal dextran assay. 2. ER was detected in 4/13 (31 per cent ) and 5/9 (56 per cent ) of the rectum and colon carcinomas analyzed, and density values ranged from 10 to 14 and from 10 to 27 fm/mg protein, respectively. Normal distal or adjacent mucosa presented similar incidence and ER density values within the tumor ranges. 3. The incidence of PR-positive samples was also higher in colon than in rectal carcinomas (44 per cent vs 23 per cent ). Normal mucosa displayed significantly higher PR titers than the corresponding tumor tissue. It seems reasonable to assume that normal colorectal mucosa may be one of the target tissues of progesterone activity. Most tumor biopsies and normal mucosa were completely AR negative, whilst GR was present in a larger fraction (63 per cent ) of tumoral specimens, occurring more commonly in colon than in rectum carcinomas. GR incidence tended to be higher in neoplasms than in normal mucosa (54 per cent vs 38 per cent in rectum and 78 per cent vs 56 per cent in colon), suggesting that glucocorticoids may be involved in the control of tumor-cell proliferation. 4. Our findings which indicate low densities of ER, PR, and absence of AR in some large bowel cancers, suggest sex hormone and endocrine independence for those cancers. The role of glucocorticoid receptors in those forms of cancer remains to be elucidated

Condicoes imunoproliferativas do intestino delgado e linfoma do Mediterraneo. / Immunoproliferative conditions of the small intestine and Mediterranean lymphoma

Os autores estudam cinco pacientes portadores de malabsorcao e diarreia que melhoraram com o emprego de antibioticos. Os referidos pacientes foram estudados atraves de tecnicas imunologicas, determinacao da perda enterica de proteinas (51Cr), avaliacao da concentracao bacteriana no delgado superior e prova da pentagastrina, ao lado de exames clinicos rotineiros.Quatro dos pacientes chegaram a laparotomia, atingindo-se os seguintes diagnosticos: tres casos de doenca de cadeia alfa, um de linfoma misto do delgado situado paraproteina IgG em um deles. Os dados clinicos, laboratoriais e histopatologicos foram comparados, formulando-se a hipotese, tendo por base essa comparacao, que a doenca de cadeia alfa ocorre em individuos com deficiencia imunologica previa. Admitem tambem, em termos hipoteticos, que a doenca, o paciente apresenta melhores condicoes imunologicas. A doenca de cadeia alfa nao corresponde sempre ao linfoma plasmocitico tendo como orientacao a classificacao de Rappaport adaptada

Alteracoes histopatologicas nas alcas ileais e jejunais de pacientes submetidos a operacao de by-pass para tratamento da obesidade. / Histopathological changes in the ileum and jejunum of patients subjected to a bypass operation for treatment of obesity

Sete pacientes submetidos previamente a "by-pass" intestinal pela tecnica de Scott para tratamento da obesidade foram reoperados num periodo de 18 meses a 3 anos por causas diversas. Ao lado de cuidadosa observacao macroscopica foram colhidas biopsias da parede do intestino delgado em locais predeterminados. Observou-se aumento do calibre e comprimento da alca funcionante em todos eles, enquanto a parte proximal do jejuno excluso estava consideravelmente reduzida em seu diametro. No segundo funcionamento observou-se hipertrofia da camada muscular e da mucosa, os vilos eram mais largos com o dobro ou mais do tamanho normal,com acentuado alongamento das vilosidades.Na parte distal do segmento excluido, proximal a anastomose com o sigmoide, a alca tinha calibre aumentado com hiperemia da serosa e intenso infiltrado linfoplasmocitario, possivelmente em funcao de contaminacao pela flora colonica O aspecto da mucosa mostrando consideravel aumento do numero intraluminar das celulas caliciformes sugere uma certa "colonizacao" desse segmento. Em dois casos, esse segmento estava recoberto por grande numero de pneumocistos

Niveis sericos de gastrina, calcio, fosforo e creatinina em pacientes portadores de insuficiencia renal cronica. / Seric levels of gastrin, calcium, phosphorus and creatinine in patients with chronic renal faillure

Os AA. dosaram gastrina serica em 41 pacientes portadores de insuficiencia renal cronica (IRC), em regime de hemodialise.Os valores medios normais de gastrina foram avaliados em grupo controle de dez individuos. Na IRC a gastrina media foi de 234,05 + ou - 285,05 pg/ml, contra 47,90 + ou - 28,16 pg/ml entre os normais, nao havendo diferenca estatisticamente significante entre os grupos. Entretanto, a distribuicao de valores normais e anormais nos dois grupos revelou-se significante pelo teste exato de Fischer. Analisam o papel do calcio, fosforo e creatinina, nao atribuindo ao calcio, em termos de hiperparatireoidismo secundario, o papel modulador da elevacao da gastrina. Os valores medios do calcio tenderam a limites relativamente baixos, com elevacao do fosforo.O papel da gastrinemia elevada nos renais cronicos, no que diz respeito a gastropatia uremica, ainda nao esta suficientemente esclarecido

Analise critica da dieta elementar e da nutricao parenteral nas enteropatias graves. / Critical analysis of elemental diet and parenteral feeding in severe enteropathies

As dietas elementares tem sido empregadas como substituto da nutricao parenteral exclusiva, em certas situacoes de falencia da funcao digestiva e absortiva do trato gastrointestinal. Tendo-se em vista o menor custo e a maior tolerabilidade atribuidas aquela dieta, os autores analisaram criticamente os efeitos de uma preparacao elementar provida de elevado teor de nitrogenio, em quatro pacientes acometidos de grave enteropatia perdedora de proteinas, dois dos quais haviam sido submetidos previamente a hiperalimentacao parenteral.A resposta nutricional foi avaliada com auxilio de parametros antropometricos, exames laboratoriais, e a excrecao urinaria de ureia e creatinina. A dieta elementar foi infundida pela tecnica de gavagem, com auxilio de uma delgada sonda de silicone, a fim de assegurar uma constancia e regularidade na oferta de nutrientes. Nao houve complicacoes metabolicas ou infecciosas do tratamento, tendo havido boa tolerancia a dieta elementar, ao lado de regressao dos fenomenos de diarreia e disenteria. Tambem os efeitos nutricionais da dieta enteral foram equivalentes aqueles proporcionados com a alimentacao intravenosa, incluindo-se sintese de massa muscular, regressao de edemas e manutencao ou melhora dos demais parametros de controle estudados. Conclui-se que a dieta elementar constitui uma alternativa importante para o manejo de enfermos com dificuldades digestivas graves, porem sem interrupcao da continuidade e do transito gastrointestinal

Nutricao enteral atraves de sondas nasojejunais. Apresentacao de uma nova sonda feita de borracha de silicone. / Enteral nutrition through naso-jejunal intubation. Presentation of a new tube made of silicone elastomers

Os autores apresentam um novo modelo de sonda para alimentacao enteral, inteiramente feito de silastic radiopaco e provido, na sua extremidade distal, de um pequeno balao contendo mercurio. Suas vantagens em relacao as sondas de alimentacao tradicionais sao: menor calibre, extraordinaria flexibilidade e biocompatibilidade e facilidade de migracao espontanea para o duodeno ou jejuno, quando desejada. Sua utilizacao em dez pacientes que dependiam de alimentacao enteral para manutencao ou melhora das suas condicoes nutritivas, revelou resposta satisfatoria ao tratamento, com ausencia de fenomenos irritativos e excelente tolerancia por parte dos enfermos propiciando uma infusao mais constante e mais segura da dieta