Immunoexpression of cyclooxygenase-1 and -2 in ulcerative colitis.

Ulcerative colitis (UC) is a disease of the colon and rectum characterized by a nonspecific chronic inflammation mediated by the concerted response of cellular and humoral events. Prostaglandins are synthesized by cyclooxygenase (COX)-1 and -2 and exhibit both pro- and anti-inflammatory activity. To evaluate COX-1 and COX-2 immunoexpression in 42 cases of UC and to correlate it with clinicopathological parameters, COX-1 and COX-2 expression was investigated by the immunohistochemistry method. Only patients with all pertinent clinical and evolutive data as well as with adequate biopsy material were included in the study. Fifteen samples of colorectal adenocarcinoma and 14 of large bowel with no histological changes were used for positive and negative controls, respectively. UC patients showed COX-1 immunoreactivity in epithelial cells in 29% of the cases and in inflammatory cells in 43%. COX-2 positivity in epithelial and inflammatory cells was found in 69% of the samples. The comparison between UC and the control groups revealed that the UC group had significantly more positive cases for COX-1 and COX-2 in inflammatory cells. Immunohistochemistry allowed the identification of COX-1 and COX-2 expression in epithelial and inflammatory cells in UC biopsies. No significant difference between COX-1 and COX-2 immunoreactivity in epithelial and inflammatory cells was observed regarding the clinicopathological parameters. COX-2 presented low expression in normal colon and high expression in colorectal adenocarcinoma. COX-2 might play a role in the pathophysiologic processes of inflammatory bowel disease and the development of neoplasia. Treatment with selective COX-2 inhibitors might be an additional option for therapy.

Immunoexpression of cyclooxygenase-1 and -2 in ulcerative colitis

Ulcerative colitis (UC) is a disease of the colon and rectum characterized by a nonspecific chronic inflammation mediated by the concerted response of cellular and humoral events. Prostaglandins are synthesized by cyclooxygenase (COX)-1 and -2 and exhibit both pro- and anti-inflammatory activity. To evaluate COX-1 and COX-2 immunoexpression in 42 cases of UC and to correlate it with clinicopathological parameters, COX-1 and COX-2 expression was investigated by the immunohistochemistry method. Only patients with all pertinent clinical and evolutive data as well as with adequate biopsy material were included in the study. Fifteen samples of colorectal adenocarcinoma and 14 of large bowel with no histological changes were used for positive and negative controls, respectively. UC patients showed COX-1 immunoreactivity in epithelial cells in 29 percent of the cases and in inflammatory cells in 43 percent. COX-2 positivity in epithelial and inflammatory cells was found in 69 percent of the samples. The comparison between UC and the control groups revealed that the UC group had significantly more positive cases for COX-1 and COX-2 in inflammatory cells. Immunohistochemistry allowed the identification of COX-1 and COX-2 expression in epithelial and inflammatory cells in UC biopsies. No significant difference between COX-1 and COX-2 immunoreactivity in epithelial and inflammatory cells was observed regarding the clinicopathological parameters. COX-2 presented low expression in normal colon and high expression in colorectal adenocarcinoma. COX-2 might play a role in the pathophysiologic processes of inflammatory bowel disease and the development of neoplasia. Treatment with selective COX-2 inhibitors might be an additional option for therapy.

[Importance of serum albumin values in nutritional assessment and inflammatory activity in patients with Crohn's disease]. / Importância da albumina sérica na avaliação nutricional e de atividade inflamatória em pacientes com doença de Crohn.

BACKGROUND: The serum albumin concentration has frequently been regarded as an indicator of nutritional status, although the hypoalbuminemia may reflect an acute phase protein response during inflammation mediated by cytokines. Both hypoalbuminemia and malnutrition are observed in Crohn's disease. OBJECTIVES: To correlate the serum albumin values to disease activity and also to nutritional status in patients with Crohn's disease. PATIENTS/METHODS: Thirty six patients were studied. Nutritional status was assessed by anthropometry measures and inflammatory activity determined by Harvey's simple clinical index and erythrocyte sedimentation rate. RESULTS: No correlation was found between malnutrition and hypoalbuminemia. The serum albumin levels correlated inversely with the disease activity. Hypoalbuminemia was 100% sensitive for detection of disease activity. CONCLUSION: This study suggests that serum albumin concentration is a very sensitive marker of inflammatory activity and not good indicator of the nutritional status in Crohn's disease. It is necessary a suitable laboratorial parameter for routine nutrition assessment in patients with this inflammatory bowel disease.

[Smoking and inflammatory bowel disease: an epidemiological case-control study]. / Tabagismo e doença inflamatória intestinal: estudo epidemiológico caso-controle.

Smoking is one of the most consistent epidemiological features related to occurrence and evolution of inflammatory bowel disease. Ulcerative colitis is accepted as a non or ex-smokers disease suggesting a protective role of tobacco against its development. In contrast there are more Crohn's disease cases between smokers. Sixty eight patients with inflammatory disease (36 ulcerative colitis; 32 Crohn's disease) and 136 patients with gastrointestinal functional disorders were matched for sex, age, scholarity and professional and religious patterns. They are divided in smokers, ex- and non-smokers. The inflammatory bowel disease patients were asked about the relationship between smoking and onset of the disease, and exposure, as passive smokers, during childhood. Smoking habit protected against ulcerative colitis (OR:0.30, IC:95%), but not against Crohn's disease (OR:0.81, P > 0.5). There was no increased risk for development of Crohn's disease between smokers; 72.7% of ex-smokers acquired ulcerative colitis and 44.4% Crohn's disease after tobacco habit has stopped. Exposure to environmental tobacco smoking during childhood did not increased the risk for ulcerative colitis (OR:0.93, P < 0.1) neither for Crohn's disease (OR:0.44, P < 0.2). Our results are similar to those of the literature related to protection of ulcerative colitis by smoking habit. Further experimental and clinic studies are in need to clarify the possible pharmacological and therapeutic action of tobacco products in this inflammatory disease.

The predictive value of serum laminin for the risk of variceal bleeding related to portal pressure levels.

BACKGROUND/AIMS: This paper presents the results of the radioimmunologic determination of laminin in serum of patients with alcoholic liver cirrhosis with a preserved hepatic function, trying to evaluate its predictive value for the risk of variceal bleeding, assessed by a portal pressure level equal to or higher than 12 mmHg. PATIENTS AND METHODS: Twenty alcoholic cirrhotic patients with a preserved hepatic function as assessed by the Child-Pugh classification, had their peripheral blood taken for radioimmunological determination of serum laminin and were submitted to hepatic vein catheterization for portal pressure measurement. RESULTS: A positive and significant correlation (r = 0.70, p < 0.001) was found between serum laminin levels (mean value + SD = 2.70 + 1.13 U/ml) and hepatic vein pressure gradient (mean HVPG + SD = 16.30 + 6.06 mmHg). Such correlation prompted us to find a value for the level of laminin that more closely represented a HVPG of 12 mmHg, a well known threshold pressure for esophageal varices bleeding. At a cut-off concentration for laminin of 2.19 U/ml, sensitivity was 73%, specificity 60%, the positive predictive value was 85% and the negative predictive value 43%. In this study population, with a prevalence of 75% of a HVPG > or = 12 mmHg, the diagnostic accuracy for such levels of serum laminin was 70%. CONCLUSIONS: Although a valid attempt in having a non invasive parameter for the investigation of portal hypertension, peripheral serum laminin alone doesn't seem to be a reliable marker for predicting portal hypertension and to assess the risk of variceal bleeding in patients with alcoholic cirrhosis.

Parasite and egg burden, hepatic collagen and histologic pattern of liver granulomas in selection III high and low antibody responder mice infected with Schistosoma mansoni

Selection III mice have particular immunological characteristics: they are high (H III) or low (L III) antibody producer animals, yet both lines display similar T cell responses and macrophage activities. We submittedthese mice to infection with Schistosoma mansoni to assess in vivo parasite and egg burden, hepatic collagen and cellular composition of granulomas in both lines. Titration of anti-Schistosoma IgG by ELISA showed remarkably higher values inH III line, at both studied periods (8th and 12th weeks post-infection). Nevertheless, the number of adult worms recovered from the portal system was similar inboth lines, being not associated with anti-Schistosoma antibody levels. There isan increase in hepatic collagen from the 8th to the 12th weeks post-infection, which is paralleled by an increase in the number of eggs in the liver. This association apparently occurs at the same radio in H III and L III animals. The most important difference found between the two lines was the outstanding contrast interms of volume and eosinophil counts in the granulomas, with lesions from H IIImice clearly being larger and containing more of these cells than LIII lesions

Parasite and egg burden, hepatic collagen and histologic pattern of liver granulomas in selection III high and low antibody responder mice infected with Schistosoma mansoni.

Selection III mice have particular immunological characteristics: they are high (H III) or low (L III) antibody producer animals, yet both lines display similar T cell responses and macrophage activities. We submitted these mice to infection with Schistosoma mansoni to assess in vivo parasite and egg burden, hepatic collagen and cellular composition of granulomas in both lines. Titration of anti-Schistosoma IgG by ELISA showed remarkably higher values in H III line, at both studied periods (8th and 12th weeks post-infection). Nevertheless, the number of adult worms recovered from the portal system was similar in both lines, being not associated with anti-Schistosoma antibody levels. There is an increase in hepatic collagen from the 8th to the 12th weeks post-infection, which is paralleled by an increase in the number of eggs in the liver. This association apparently occurs at the same ratio in H III and L III animals. The most important difference found between the two lines was the outstanding contrast in terms of volume and eosinophil counts in the granulomas, with lesions from H III mice clearly being larger and containing more of these cells than LIII lesions.

Treatment of duodenal ulcer with omeprazole or ranitidine in a Brazilian population: a multicenter double-blind, parallel group study.

Two hundred and forty-one patients with at least one ulcer at stage A1 or A2, measuring at least 5 mm in its larger diameter, were included in this Brazilian double-blind randomized study. Patients received omeprazole 20 mg in the morning (n = 120) or ranitidine 300 mg at night (n = 121) for 2 wk; unhealed ulcers were treated for an additional 2 wk. At the end of 4 wk, unhealed ulcers were treated openly with omeprazole 20 mg o.m. for 4 wk. Healing rates at 2 and 4 wk were 67.3% and 92.9% for omeprazole and 39.8% and 82.0% for ranitidine (per protocol analysis). Results were similar when analyzed as intention to treat (p significant in favor of omeprazole). Epigastric day-time pain was the most common of all symptoms (89.2%), but only heartburn at day 15 showed a significantly better response to omeprazole than to ranitidine. A multivariate analysis (logit analysis) showed that the odds in favor of healing were greater for small ulcers, nonsmokers, and omeprazole treatment.

Very-low dose antacid in treatment of duodenal ulcer. Comparison with cimetidine.

Antacid (AA) in a very low dose (88 mmol/day) was compared to the standard 800-mg dose of cimetidine in healing duodenal ulcers. The influence of sex, age, symptom duration at entry, night pain, smoking, coffee consumption, and alcohol on ulcer healing was studied. The antacid was given in two different schedules: group I--20 ml 1 hr after breakfast and at bedtime; group II--10 ml 1 hr after breakfast and lunch and 20 ml at bedtime. Cimetidine (group III) was given in two divided doses: 400 mg 1 hr after breakfast and 400 mg at bedtime. Endoscopic control was performed after four weeks and, if necessary, after eight weeks of treatment. The healing rate after four weeks of treatment was, respectively, for groups I, II, and III, 45.5%, 55.8%, and 69.4% (group I = group II, and group III different from groups I and II). After eight weeks of treatment the healing rate was 61.5%, 80.8%, and 88.0% for groups I, II, and III, respectively (group II = group III, and group I different from groups II and III). Except for group I, smoking did not influence healing rate. Age, sex, symptoms at entry, night pain, and coffee consumption did not influence the treatment results. The authors concluded that the very low dose of magaldrate (88 mmol/day), when administered in three divided doses (10 ml after breakfast and lunch and 20 ml at bedtime) for eight weeks was as effective as 800 mg of cimetidine (400 mg twice a day) in healing duodenal ulcer.

[Histochemical study of the skeletal muscle in chronic alcoholism]. / Estudo histoquímico do músculo esquelético no alcoolismo crônico.

Twenty-two chronic alcoholic patients were assessed by neurologic examination and muscle biopsy. The patients manifested proximal muscular weakness to a variable extent. One case presented as an acute bout of myopathy, according to the Manual Muscle Test, MMT. The most prominent histologic feature observed was muscle atrophy (95.3%) better evidenced through the ATPase stain with the predominance of type II A fibers (71.4%). Lack of the mosaic pattern (type grouping) seen in 76% of the cases and an important mitochondrial proliferation with intrasarcoplasmatic lipid accumulation in 63% of the patients. In case of acute presentation of muscle weakness the pathological substrate is quite different, i.e. presence of myositis mainly interstitial characterized by lymphoplasmocytic infiltrate and several spots of necrosis like Zencker degeneration. Based on histologic criteria, our data suggest that: the main determinant of muscle weakness seen in chronic alcoholic patients is neurogenic in origin (alcoholic polyneuropathy); the direct toxic action of ethanol under the skeletal muscle is closely related to the mitochondrial metabolism; the so-called acute alcoholic myopathy has probably viral etiology.

Estudo histoquímico do músculo esquelético no alcoolismo crônico / Histochemical study of the skeletal muscle in chronic alcoholism

Vinte e dois pacientes alcoólatras crônicos foram submetidos a exame clínico neurológico e biópsia muscular. Eles apresentavam graus variáveis de fraqueza muscular proximal (cinturas escapular e pélvica), tendo um deles evoluído com quadro agudo de miopatia (avaliaçäo pelo 'Manual Muscle Test', MMT). A principal alteraçäo histológica observada é melhor evidenciada pela coloraçäo da ATPase: atrofia muscular (95,3%), predominando nas fibras do tipo II A (71,4%) e, em 76% dos casos, alteraçäo da imagem em mosaico à custa de agrupamentos de fibras musculares de mesmo tipo histoquímico ('type-grouping'). Secundariamente, em 63% dos casos, observa-se proliferaçäo mitocondrial e conseqüente acúmulo lipídico intra-sarcoplasmático. No caso de instalaçäo aguda da fraqueza muscular, o substrato anátomo-patológico é completamente diferente: presença de miosite, predominantemente intersticial, caracterizada por infiltrado linfoplasmocitário e numerosas imagens de necrose tipo degeneraçäo cérea de Zencker. Baseando-se em critérios histológicos, nossos dados sugerem que: a principal gênese da fraqueza muscular observada em pacientes alcoólatras crônicos tem natureza neurogência (polineuropatia alcoólica); a atuaçäo tóxica direta do etanol sobre o músculo esquelético está intimamente relacionada ao metabolismo mitocondrial; a chamada miopatia aguda alcoólica tenha etiologia inflamatória, do tipo viral

Murine schistosomiasis mansoni: estimation on some immunohistological parameters of small bowel granulomas and renal parenchyma.

One hundred and twenty five mice were divided into three groups: uninfected (I), and infected with 30 (II) and 60 (III) cercariae. Jejunal, ileal and renal sections were analyzed by direct immunofluorescence technique, aiming the detection of gamma globulins and complement C3. Intestinal sections were also stained by hematoxylin-eosin, during some periods of disease. The cellular composition of the jejunal and ileal granulomas seemed very similar, with many eosinophils and an increased number of mononuclear cells later on. The histological evaluation of these sections showed that the ileum may hold greater number of eggs, possibly being more affected than the jejunum. The results also suggest a mixed mechanism to the formation of intestinal granulomas, both cell and antibody mediated.

Vestibular disorders caused by defective enzyme mechanisms in the small intestine.

A group of patients suffering from long periods of unsteadiness and presenting hyperreflexia in response to torsion swing and/or caloric stimulations were found to have abnormal results in glucose and lactose tolerance tests, but normal or reduced insulin liberation. Biopsies of the jejunal mucosa have shown abnormal enzyme activity or deficiencies in transport mechanisms. The use of a diet suited to each specific deficiency resulted in a high percentage of relief from the vestibular symptoms of these patients.