Secondary hyperoxaluria due to pancreatic insufficiency.

BACKGROUND: In this article, we present two cases of patients with acute renal insufficiency with a history of exocrine pancreatic insufficiency. In one case, this was caused by pancreaticoduodenectomy; in the other, by alcohol abuse. Neither patient had considerable proteinuria or haematuria. Their renal biopsies showed tubulopathy with widespread oxalate crystals, characterised by their birefringence in light microscopy. Restricting oxalate intake and prescribing oxalate binding agents reduced serum oxalate levels. Renal function partially recovered in both patients. Oxalate nephropathy is associated with exocrine pancreatic insufficiency, gastric and pancreatic surgery, and inflammatory bowel disease. Normally, dietary calcium binds oxalate to form calcium oxalate, which is excreted in the stool. In patients with pancreatic insufficiency, fatty acids bind calcium instead, allowing oxalate to be absorbed in the colon. The resulting hyperoxaluria can cause oxalate crystal formation, tubulopathy, and renal insufficiency. Treatment relies on decreasing the amount of absorbable oxalate in the intestinal lumen, as well as lowering urinary oxalate concentrations. CONCLUSION: Secondary hyperoxaluria is a common cause of renal insufficiency and should be considered in patients with a medical history of pancreatic insufficiency and progressive kidney injury.

Viral kinetics during the first weeks of pegylated interferon and ribavirin treatment can identify patients at risk of relapse after its discontinuation: new strategies for such patients?

BACKGROUND: Pegylated interferon (PEG-IFN) and ribavirin is the most effective treatment for chronic hepatitis C virus (HCV) hepatitis, but the rate of sustained virological response (SVR) remains approximately 50%, and 15-20% of all treated patients have a virological relapse after completing the treatment. Studies on the SVR have failed to discriminate between non-responders and relapsers. AIMS: To identify the risk factors for relapse among patients with an end-of-treatment response (ETR). METHODS: We retrospectively analyzed 281 patients consecutively treated with PEG-IFN and ribavirin with a follow-up period of at least 24 weeks. The baseline details collected on each patient included demographic data, histological features, and biochemical profiles. RESULTS: Forty-six patients (16.4%) relapsed during the first 6 months of follow-up after discontinuing the therapy. Relapser patients were significantly older, had more steatosis, fibrosis, and showed significantly lower rapid virological response (RVR) rates compared with SVR patients. By logistic regression analysis, only the absence of RVR was found to be significantly associated with relapses in both subgroups of patients with genotypes 1 and 4 (p < 0.004) and those with genotypes 2 and 3 (p < 0.006). Severe fibrosis was also predictive of relapsing disease, but only for genotypes 2 and 3 patients (p < 0.003). During the treatment, serum HCV-RNA decreased more rapidly in patients with SVR compared to non-responder and relapser patients (p < 0.001). Interestingly, relapser patients exhibited an intermediate serum HCV-RNA decay during the first 4 weeks of therapy. CONCLUSION: Among HCV patients treated with PEG-IFN and ribavirin, the absence of RVR was the most important independent predictor of relapse, independent of the HCV genotype. In the subgroup of genotypes 2 and 3 patients, the severity of fibrosis was also an important factor associated with the relapse rate.

Hyperinsulinaemia reduces the 24-h virological response to PEG-interferon therapy in patients with chronic hepatitis C and insulin resistance.

Insulin resistance (IR) reduces response to pegylated-interferon (PEG-IFN)/ribavirin in chronic hepatitis C (CHC), but the mechanisms are still undefined. We examined the relationship between baseline insulin levels, the main component affecting homeostasis model of assessment - insulin resistance (HOMA-IR) for assessment of IR in non-diabetic patients, and the 'acute' virological response to PEG-IFN measured 24 h after the first injection and taken as correlate of intracellular interferon signalling. In 62 patients treated with PEG-IFN/Ribavirin, serum insulin and HOMA-IR were assessed at baseline, while hepatitis C virus (HCV)-RNA was measured at baseline and 24 h, 1, 2, 4 and 12 weeks after treatment initiation. Sustained virological response was examined 24 weeks after therapy discontinuation. Mean baseline insulin was 11.52 +/- 8.51 U/L and mean HOMA-IR was 2.65 +/- 2.01 both being significantly higher with advanced liver fibrosis. Hepatitis C virus-RNA decay observed 24 h after the first injection of PEG-IFN was significantly lower (0.7 +/- 0.8 log) in patients with HOMA > or =3 compared with those with HOMA <3 (1.7 +/- 0.8, P = 0.001). A highly significant (r = -0.42) inverse correlation was observed between baseline insulin levels and the 24-h HCV-RNA decay. The difference in early viral kinetics between patients with HOMA > or =3 or <3 resulted in a significant difference in the percentage of patients achieving rapid (week 4) and sustained virological response. Multivariate analysis, inclusive of patient age, HCV genotype and fibrosis stage, identified baseline insulin levels as the main independent variable affecting the 24-h response to PEG-IFN. Hyperinsulinaemia reduces the cellular response to Pegylated-interferon in CHC with IR. Strategies to reduce insulin levels before initiation of treatment should be pursued to improve efficacy of anti-viral treatment.

Use of alternative and complementary therapies by inflammatory bowel disease patients in an Italian tertiary referral centre.

BACKGROUND: Alternative and complementary therapies are increasingly used by patients with inflammatory bowel disease, but no data are available on their use in Italy. AIM: To ascertain the prevalence and pattern of the use of alternative and complementary therapies, and demographic and clinical factors associated with their use in a large sample of Italian inflammatory bowel disease patients. METHODS: A structured questionnaire was administered to a cohort of outpatients at a tertiary referral centre. RESULTS: Five hundred and fifty-two patients completed the questionnaire; 156 (28%) reported using alternative and complementary therapies, which mainly involved homeopathy (43.6%), followed by controlled diets or dietary supplements (35.5%), herbs (28.2%), exercise (25.6%) and prayer (14.7%). Alternative and complementary therapies were used to ameliorate intestinal symptoms (52.5%), in the hope of being cured (41%) and to reduce the intake of drugs (39.7%). An improvement in well-being (45.5%) and inflammatory bowel disease symptoms (40.3%) were the most commonly reported benefits. A higher education (p=0.027), a more frequently relapsing disease (p=0.001) and dissatisfaction with the doctor's communication (p=0.001) correlated with alternative and complementary therapy use. Non-compliance with conventional drugs, disease severity and curiosity regarding novel therapies were predictors of alternative and complementary therapy use. CONCLUSIONS: Alternative and complementary therapies are frequently used by Italian inflammatory bowel disease patients. Doctors should improve their empathy and their understanding about possible benefits of alternative and complementary therapies.

Diferencias étnicas en inteligencia emocional percibida en los Estados Unidos y México / Ethinic group differences in perceived emotional intelligence within the united states and Mexico

This study investigted etnic differences in the United States and Mexico on Perceived Emotional Intelligence (PEI). The invesigation exploed te hypothesis f ethnic variability in PEI by having African Americans, Latino Americans, Whites and Mexicans complete the Trait Meta-Mood Scale (TMMS) on three factors: Attention, Clarity, and Repair of emotions. A total of 519 participants volunteered to complet the TMMS. The resutls showed that for Attention and Clarity there were significant differences among ethnic groups with Mexicans scoring lower than African Americans, Latino Americans and Whits. However, on Repair, there were no significant differences among ethnic groups. Additionally, results indicated ethnic groups. Additionally, results indicated gender difference between women and men on Attention and Clarity. Women socred hhger than men on Attention and lower than men on Clariy. These findings suggest that particular ethnic groups can have notable differences in certain domains of PEI. However, researchers shoulde be guarded in assuming that particualr ethinic groups can have greater PEI, without first conrolling essential socio-demographic variables(AU)

The cognitive correlates of affect intensity, together with the relationships between this variable and socio-demographic and outcome variables such as, respectively, age and anxiety remian understudied. This work analyzes age diffferences in affect intensity and in two types of cognitive coping strategies in threatening situations; vigilance and distraction. Also, the relationship between this two variables and their association with the level on anxiety is explored. Fifty five younger and 51 older subjects (aged 60 and more) participated in the study. The resuls revealed significant age differences in the assessed variables, as well as differential interrelationships between them in the 2 age groups. Also, affect intesity and cognitive coping apperar to be more related to anxiety in the older subjects group. The relevance of age in the analysis of the relationships between psychological construct is highlighted(AU)

Nutritional state and energy balance in cirrhotic patients with or without hypermetabolism. Multicentre prospective study by the 'Nutritional Problems in Gastroenterology' Section of the Italian Society of Gastroenterology (SIGE).

BACKGROUND AND AIMS: A total of 334 stable, compensated cirrhotic patients admitted to 10 Italian Gastroenterology Units were included in a prospective study to evaluate nutritional state and energy balance in liver cirrhosis. MATERIALS AND METHODS: Nutritional state and calorie intake were examined in the total population, while adequacy of calorie intake versus measured total energy expenditure was evaluated in a comparable subpopulation and in 40 matched controls, by computing the energy balance. RESULTS: Our data demonstrated that: (i) malnutrition was present in 25% of the total patients and significantly correlated with the Child's group (A=16%; B=25%; C=44%); (ii) the type of malnutrition is influenced by mBEE: normometabolic patients exhibit a significant (p<0.005) reduction of mid-arm fat area while both hypermetabolic and hypometabolic patients show a significant (p<0.005) decline in kg of free fat mass; (iii) normometabolic and hypometabolic patients have a negative energy balance, due to a high level of physical activity (127+/-14 kJ) in the first group and a reduced energy intake/kg body weight (102+/-12 kJ) in the second; (iv) hypermetabolic patients have a positive energy balance due to decreased daily physical activity/kg body weight (108+/-28 kJ); (v) malnourished and normometabolic patients eat a significantly (p<0.05) reduced percentage of protein whereas malnourished and hypermetabolic patients eat a significantly increased percentage of fat (p<0.05). CONCLUSION: Although multivariate regression analysis confirms that the Child-Pugh's score is a better independent predictor of malnutrition, the measure of REE, TEE, calorie intake and energy balance need to be routinely performed in cirrhotic patients, in order to recognise hypermetabolic and hypometabolic patients (approximately 30%) in whom the nutritional and metabolic parameters are indispensable as a basis for designing and prescribing personalised nutritional strategies that can treat muscle malnutrition and thus improve the morbidity and mortality rates.

Transcriptional downregulation of tight junction protein ZO-1 in active coeliac disease is reversed after a gluten-free diet.

UNLABELLED: Coeliac disease is an autoimmune enteropathy characterized by an enhanced permeability of the intestinal epithelial barrier. In epithelial cells paracellular permeability is regulated by intercellular tight junction. The cytoplasmic protein ZO-1 interacts directly with F-actin and plays a pivotal role in the structural and functional organization of tight junction. AIM: The aim of this study was to investigate the expression and localization of ZO-1 in the intestinal mucosa of coeliac patients. PATIENTS AND METHODS: Twenty patients with active coeliac disease, seven of whom underwent a repeat biopsy following a gluten-free diet and 27 control subjects, were studied. In all subjects, three biopsies were obtained from distal duodenum during upper gastrointestinal endoscopy. ZO-1 protein localization and levels were detected by immunofluorescence followed by confocal microscopy analysis and immunoblotting. ZO-1 mRNA expression was assessed by RT-PCR. F-actin distribution was also investigated. RESULTS: In patients with active coeliac disease, both ZO-1 protein levels and mRNA were clearly reduced. Cytoskeletal organization was disrupted with F-actin staining concentrated at the subcortical and basal surface regions. Abnormalities in ZO-1 expression and actin organization were reversed after a gluten-free diet. CONCLUSIONS: In active coeliac disease, ZO-1 protein expression is downregulated at the transcriptional level in association with F-actin redistribution. These changes are completely reversed after a gluten-free diet and could contribute to the increased intestinal paracellular permeability observed in this disorder.

Butyrate downregulates alpha2beta1 integrin: a possible role in the induction of apoptosis in colorectal cancer cell lines.

BACKGROUND: Integrins mediate cell matrix adhesion and regulate cell growth and survival. In colonic epithelial cells, alpha(2)beta(1) integrin controls glandular differentiation and proliferation. Butyrate stimulates differentiation and induces apoptosis in vitro. AIMS: We investigated whether butyrate induction of apoptosis was associated with perturbation of integrin mediated cell matrix adhesion. METHODS: Three colonic cancer cell lines (SW1222, SW620, LS174T) were studied. Adhesion to extracellular matrix proteins, expression of alpha(2)beta(1) integrin, and apoptosis were studied in adherent cells after treatment with 4 mM butyrate. RESULTS: Butyrate decreased the attachment to type I collagen in SW620 cells and type I and IV collagen in LS174T cells. The decreased cell attachment was associated with downregulation of alpha(2)beta(1) integrin and increased apoptosis in adherent cells. No changes in alpha(2)beta(1) expression or matrix adhesion were seen in SW1222 cells, which were also found to be less sensitive to butyrate induction of apoptosis. Downregulation of alpha(2)beta(1) integrin preceded the detection of apoptosis. CONCLUSION: Apoptosis induced by butyrate is associated with downregulation of expression and functional activity of alpha(2)beta(1) integrin. Perturbation of cell matrix adhesion may be a novel mechanism by which butyrate induces apoptosis in colorectal cancer cells.

Histological features after liver transplantation in alcoholic cirrhotics.

BACKGROUND/AIMS: Though alcoholic cirrhosis is a common indication for liver transplantation, it carries the risk of alcohol recidivism and consequent graft failure. This study aims to evaluate the effect of alcohol recidivism on survival rates and histological parameters in patients transplanted for alcoholic cirrhosis, with and without hepatitis C virus (HCV) infection. METHODS: Fifty-one out of 189 consecutive transplanted patients underwent psychosocial evaluation and liver biopsy at 6 and 12 months, then yearly after transplantation. RESULTS: The cumulative 84 month survival rate was identical in patients transplanted for alcoholic (51%) and non-alcoholic cirrhosis (52%). No difference emerged between anti-HCV negative vs. positive alcoholic cirrhosis patients. Psycho-social evaluation revealed alcohol recidivism in 11/34 long-term survivors, but this did not affect overall survival rate in patients with or without HCV. In anti-HCV negative cases, fatty changes and pericellular fibrosis were significantly more common in heavy drinkers than in occasional drinkers and abstainers. When HCV status was considered regardless of alcohol intake, fibrosis was significantly more frequent in patients with HCV. CONCLUSION: Alcohol recidivism after transplantation in alcoholic cirrhosis patients does not affect survival, irrespective of HCV status. Fatty changes and pericellular fibrosis are the most relevant histological signs of heavy alcohol intake.

Reduced plasma antioxidant concentrations and increased oxidative DNA damage in inflammatory bowel disease.

BACKGROUND: Oxidative stress is believed to play a key role in the pathogenesis of inflammatory bowel disease (IBD)-related intestinal damage. Circulating antioxidants may have a role to play in preventing free radical-mediated tissue injury. METHODS: Plasma vitamin A, E and carotenoid concentrations, leukocytic genomic damage and 8-hydroxy-deoxy-guanosine (8-OHdG) concentration were determined in 46 ulcerative colitis (UC) patients, 37 Crohn disease (CD) patients and 386 controls. A 20 ml blood sample was taken from each subject for antioxidant and 8-OHdG measurements. A food frequency questionnaire was administered to a sample of subjects from each group to evaluate daily intake of dietary compounds. RESULTS: Antioxidant concentration was significantly reduced in IBD patients, particularly in those with active disease, with respect to controls (P < 0.0001). 8-OHdG concentrations were significantly increased in IBD patients compared to controls, independent of disease activity (P < 0.05). No correlation was found between antioxidant and 8-OHdG concentrations. Carotenoid concentrations were significantly reduced in malnourished IBD patients (0.89 +/- 0.14 micromol/l) compared to patients with normal or high body mass index (1.83 +/- 0.12 micromol/l; P < 0.05), independent of disease activity or extension. Protein, fruit and vegetable intakes of IBD patients were significantly lower than those of controls. CONCLUSIONS: Depletion of antioxidants is likely to be important in the pathophysiology of IBD: UC and CD patients show increased free radical peripheral leukocyte DNA damage and decreased plasma antioxidant defenses. These results indicate the necessity of further studies to establish whether optimal vitamin status may improve the clinical course of UC and CD.

Long-term medical and psycho-social evaluation of patients undergoing orthotopic liver transplantation for alcoholic liver disease.

The major concern in transplanting patients with alcoholic liver disease (ALD) is the high rate of alcohol recidivism. Our aim was to assess the long-term outcome of liver transplantation (OLT) in a group of ALD patients in terms of post-OLT alcohol recidivism and its relationship with pre-OLT psychosocial variables and medical follow up. Fifty-one ALD patients underwent strict medical and psychosocial evaluation before and after OLT. Alcohol abuse was recorded in 60% and alcohol dependence in 40% of patients before OLT. The 5-year survival was similar to the one observed in non-ALD transplanted patients (64 vs 56%). Alcohol recidivism was observed in 33% of transplanted patients, 64% of whom were occasional and 36% were heavy drinkers. The admission of alcoholism by the patient and his/her family prior to OLT significantly predicted abstinence after OLT. A multidisciplinary approach evaluating medical and psycho-social variables before OLT and a close follow up after OLT are mandatory for ALD patients.

High plasma levels of alpha- and beta-carotene are associated with a lower risk of atherosclerosis: results from the Bruneck study.

BACKGROUND AND PURPOSE: A large number of studies have contributed to the hypothesis that carotenoids, vitamins A and E are protective against atherosclerosis by acting as antioxidants. The aim of this study was to assess the relationship between plasma levels of carotenoids (alpha- and beta- carotene, lutein, lycopene, zeaxanthin, beta-cryptoxanthin), vitamins A and E, and atherosclerosis in the carotid and femoral arteries. METHODS: This prospective and cross sectional study involved a randomly selected population sample of 392 men and women aged 45-65 years. Carotid and femoral artery atherosclerosis was assessed by high-resolution duplex ultrasound. RESULTS: alpha- and beta- carotene plasma levels were inversely associated with the prevalence of atherosclerosis in the carotid and femoral arteries (P=0.004) and with the 5-year incidence of atherosclerotic lesions in the carotid arteries (P=0.04). These findings were obtained after adjustment for other cardiovascular risk factors (sex, age, LDL (low density lipoproteins), ferritin, systolic blood pressure, smoking, categories of alcohol consumption, social status, C-reactive protein). Atherosclerosis risk gradually decreased with increasing plasma alpha- and beta-carotene concentrations (P=0.004). No associations were found between vitamin A and E plasma levels and atherosclerosis. CONCLUSIONS: This study provides further epidemiological evidence of a protective role of high alpha- and beta- carotene in early atherogenesis.

Plasma antioxidant levels in chronic cholestatic liver diseases.

BACKGROUND: [corrected] A predictable consequence of cholestasis is malabsorption of fat-soluble factors, (vitamins A, D, E, K) and other free radical scavengers, such as carotenoids. It has been suggested that oxygen-derived free radicals may be involved in the pathogenesis of chronic liver damage. AIMS: (i) To evaluate retinol, alpha-tocopherol and carotenoid plasma levels in two groups of patients with chronic cholestatic liver disease (primary biliary cirrhosis and primary sclerosing cholangitis); (ii) to compare the respective plasma levels with those of the general population; (iii) to correlate the plasma levels with disease severity. METHODS: A total of 105 patients with chronic cholestasis were included in the study: 86 with primary biliary cirrhosis (81 female, five male, mean age 55.5 +/- 11 years), 19 with primary sclerosing cholangitis (seven female, 12 male, mean age 35 +/- 11 years; six patients had associated inflammatory bowel disease); 105 sex- and age-matched subjects from the general population in the same geographical area (88 female, 17 male, mean age 51.3.5 +/- 10 years) served as controls. Carotenoids (lutein zeaxanthin, lycopene, beta-carotene, alpha-carotene, beta-cryptoxanthin), retinol and alpha-tocopherol were assayed by high-pressure liquid chromatography. A food frequency questionnaire was administered to each subject to evaluate the quality and the quantity of dietary compounds. Data were processed by analysis of variance and linear regression analysis, as appropriate. RESULTS: Both primary biliary cirrhosis and primary sclerosing cholangitis patients had significantly lower levels of retinol, alpha-tocopherol, total carotenoids, lutein, zeaxanthin, lycopene, alpha- and beta-carotene than controls (P < 0.0001). Among the cholestatic patients, no significant difference in the concentration of antioxidants was observed between primary biliary cirrhosis and primary sclerosing cholangitis subjects. Anti-oxidant plasma levels were not affected by the severity of the histological stage in primary biliary cirrhosis, but a negative correlation was found between total carotenoids and both alkaline phosphatase (ALP) and gammaglutamyl transpeptidase (GGT) (P < 0.013 and P < 0.018, respectively). Within the primary sclerosing cholangitis group, no correlation was found between total carotenoids and cholestatic enzymes. Nutritional intake in cholestatic patients was comparable to controls, including fruit and vegetable intake. CONCLUSIONS: Although no clinical sign of deficiency is evident, plasma levels of antioxidants are low in cholestatic patients even in early stages of the disease. This is probably due to malabsorption of fat-soluble vitamins, as well as other mechanisms of hepatic release, suggesting the need for dietary supplementation.

Intestinal permeability test as a predictor of clinical course in Crohn's disease.

OBJECTIVE: The clinical course of Crohn's disease is often unpredictable. The aim of this study was to select the most useful parameters able to predict clinical relapses. METHODS: One hundred-thirty Crohn's disease patients in clinical remission were followed every 4 months for 2 yr or until clinical relapse. Demographic and clinical data were recorded and intestinal permeability (lactulose/mannitol [L/M] test) and biochemical tests (white blood cell count, erythrocyte sedimentation rate, C-reactive protein, alpha1 acid glycoprotein, and serum iron) were performed at study entry. A subgroup of 54 patients had clinical follow-up and repeated tests every 4 months. RESULTS: Fifty-two patients (40%) relapsed during the 2-yr follow-up. A significant correlation was found between relapse and gender (p = 0.030) but not between relapse and age, extent and type of disease, previous surgery, or therapy. Increased L/M test (p = 0.0001) and decreased serum iron level (p = 0.0057) were associated with clinical relapse. Time-dependent analysis, performed on patients receiving serial evaluation, showed that L/M test alteration was the only variable that could predict a relapse (RR 8.84, 95% confidence interval [CI] 1.41-53.37; p < 0.05). CONCLUSIONS: The L/M test identifies Crohn's disease patients in apparent remission, but with a high risk of clinical relapse, better than clinical and biochemical indices. Different treatment strategies might be suggested for this subgroup of patients.

Oxygen-derived free radical production by peripheral blood neutrophils in chronic cholestatic liver diseases.

BACKGROUND/AIMS: Patients with chronic cholestasis, particularly those with associated cirrhosis, are susceptible to infectious complications. From animal models it has been postulated that cholestasis affects systemic polymorphonuclear leukocyte (PMNL) function by impeding chemotaxis, phagocytosis and superoxide release, which are necessary for an adequate immune response. The aim of this study was to evaluate neutrophil activity in the production of oxygen-derived free radicals in chronic cholestatic liver diseases. METHODOLOGY: The following groups were included in the study: 27 primary biliary cirrhosis (PBC) patients, 12 primary sclerosing cholangitis (PSC) patients, and 3 control groups (29 healthy subjects, 19 patients with HCV-related cirrhosis and 23 ulcerative colitis (UC) patients). Peripheral neutrophils were isolated from heparinized blood samples and PMNL activity was measured by free radical production, using a chemiluminometer, after stimulation with fMLP, PMA and Zymosan. The effect of liver disease severity and degree of cholestasis on PMNL function was also evaluated. RESULTS: Both PBC and PSC patients exhibited a normal PMNL activity compared to healthy subjects after the three stimuli used. In PBC patients only (but not in PSC patients), the histological stage of the disease seems to positively influence ROS production. Stage IV PBC patients showed a significantly higher PMNL activity compared to HCV-related cirrhotic patients. PSC patients failed to show any difference according to the association with UC. CONCLUSIONS: The increased susceptibility to bacterial infections in patients with chronic cholestatic liver disease is not related to an impaired PMNL activity. However, our findings may support the influence of biohumoral factors (cytokines?) on PMNL activation.

Ki-67 and c-jun expression in pancreatic cancer: a prognostic marker?

The proto-oncogene c-jun is involved in cell proliferation and Ki-67 antigen permits determination of the proportion of proliferating tumour cells. The expression of c-jun and Ki-67 in pancreatic cancer and their relation with tumour histological features and patients survival were evaluated. Specimens were obtained as follows: 14 pancreatic cancer from patients radically operated, 8 liver metastases from subjects submitted to palliation, 5 normal pancreas from organs donors and 5 chronic pancreatitis. Ki-67 and c-jun were studied by immunohistochemistry. The percentage of tumour cells stained for c-jun was increased in 11/14 cases. A high c-jun expression was more frequently found in liver metastases than in pancreatic cancer tissue (p=0.031). The frequency of high c-jun expression was more elevated in short-term as compared to long-term survivors (Fisher's exact test, p=0.031 and log-rank, p=0.03). The percentage of tumour positive cells for Ki-67 showed a mean value of 12.8% in primary pancreatic cancer and was lower than in the liver metastases (32.5%) (p=0.029). Significantly lower values were found in long-term (6.5%) as compared to the short-term survivors (18.1%) (p=0.032 and log-rank, p=0.006). A positive relation was demonstrated with stage (p<0.05), lymph node state (p=0.045) and perineural invasion (p=0.0001). In the multivariate analysis the Ki-67 staining was the most important determinant of long-term survival (p=0.005). c-jun and Ki-67 are overexpressed in pancreatic carcinoma, but only Ki-67 is a strong predictive factor.

Effect of moderate exercise on Crohn's disease patients in remission.

BACKGROUND: Physical exercise may exacerbate the disturbed homeostasis of Crohn's disease patients. AIM: To examine the effect of moderate physical exercise on gastrointestinal function in a group of Crohn's disease patients in remission. PATIENTS AND METHODS: The effect of one-hour's exercise at a maximum of 60% oxygen consumption was evaluated in six males with ileal Crohn's disease in remission on orocaecal transit time (breath test to lactulose), intestinal permeability (6-hours' urinary excretion of a sugar mixture of lactulose/mannitol), polymorphonuclear leucocytes function (peripheral blood chemiluminescence), lipoperoxidation (plasma malondialdehyde) and antioxidant trace elements (urinary and plasma zinc and copper concentrations). Six healthy age-matched subjects served as controls. RESULTS: Exercise did not elicit subjective symptoms or changes in intestinal permeability and lipoperoxidation. Orocaecal transit time increased after exercise in Crohn's disease patients (72 min +/- 30 vs 100 min +/- 34) with no significant difference from controls (77 min +/- 20 vs 83 min +/- 23). Neutrophils, primed pre-exercise in Crohn's disease patients showed an increased post-exercise chemiluminescence similar to controls. Zinc urinary output significantly increased after exercise in Crohn's disease patients and remained unchanged in control subjects. CONCLUSIONS: Moderate aerobic exercise has no significant effect on the gastrointestinal parameters examined. However, basal neutrophil activation and exercise in Crohn's disease patients may trigger an excessive production of oxygen metabolites. Moreover, exercise may contribute to an increased risk of zinc deficiency.

Experimental colitis increases small intestine permeability in the rat.

Small intestine permeability is frequently altered in patients with Crohn's disease and is thought to play a pathogenic role. The aim of this study was to investigate the permeability and structure of small intestine tight junctions (TJ) in an animal model of chronic distal colitis. Seven days after colitis induction with trinitrobenzenesulfonic acid/ethanol, the duodenal and ileal TJ were studied by means of transmission electron microscopy using lanthanum nitrate, freeze fractures, and immunohistochemistry of occludin, ZO-1, and cingulin. Animals treated with intrarectal ethanol alone served as controls. In controls, 7.5% of duodenal and 9.6% of ileal TJ were permeable to lanthanum, whereas in colitis, permeability increased significantly (79.5% and 72.9%, respectively; p < 0.001, both segments compared with controls). In colitis, the percentage of "leaky" junctions in duodena as well as in terminal ilea correlated positively with the macroscopic colon damage score (p < 0.02 and p < 0.005, respectively). Freeze-fracture analysis and immunohistochemistry of cingulin and ZO-1 did not reveal any difference between control and treated animals, whereas the signal of the transmembrane protein occludin was found to be disrupted and irregular in both small intestine segments. Distal colitis induces an increase of TJ permeability throughout the entire small intestine, and the extent of alterations correlates with colonic damage. Alterations in the transmembrane protein occludin seem to be responsible for the observed changes. Further investigation is needed to elucidate the mechanism of TJ alterations by a remote focus of inflammation.

Hepatocyte tight-junctional permeability is increased in rat experimental colitis.

BACKGROUND & AIMS: Hepatobiliary complications occur in inflammatory bowel disease and may be caused by the translocation of intestinal toxins from portal blood into bile through leaky hepatocyte tight junctions. The role of tight junctions in the pathogenesis of hepatobiliary complications in experimental inflammatory bowel disease was investigated. METHODS: Colitis was induced in rats by intracolonic instillation of trinitrobenzene sulfonic acid. The function of hepatocellular tight junctions was evaluated in perfused livers by measuring early (paracellular) horseradish peroxidase excretion into the bile and by electron microscopy and semiquantitative analysis of lanthanum penetration through the tight junction and into bile canaliculi. Immunofluorescent localization of cingulin and ZO-1 was used to study the structure of hepatocyte junctions. RESULTS: Colitis was associated with increased serum bilirubin and bile acid concentrations, a 2.5-fold increase in paracellular biliary excretion of horseradish peroxidase, and a ninefold increase in lanthanum permeability. Liver histology and cingulin and ZO-1 localizations were similar to normal liver. CONCLUSIONS: Experimental colitis is associated with hepatobiliary complications and an increased hepatocyte tight junctional permeability to horseradish peroxidase and lanthanum. Subtle alterations in tight junction function may be involved in the pathogenesis of hepatobiliary injuries in inflammatory bowel disease.