Geosocial Features and Loss of Biodiversity Underlie Variable Rates of Inflammatory Bowel Disease in a Large Developing Country: A Population-Based Study.

BACKGROUND: The epidemiology of inflammatory bowel disease (IBD) in developing countries may uncover etiopathogenic factors. We investigated IBD prevalence in Brazil by investigating its geographic, spatial, and temporal distribution, and attempted to identify factors associated with its recent increase. METHODS: A drug prescription database was queried longitudinally to identify patients and verify population distribution and density, race, urbanicity, sanitation, and Human Development Index. Prevalence was calculated using the number of IBD patients and the population estimated during the same decade. Data were matched to indices using linear regression analyses. RESULTS: We identified 162 894 IBD patients, 59% with ulcerative colitis (UC) and 41% with Crohn's disease (CD). The overall prevalence of IBD was 80 per 100 000, with 46 per 100 000 for UC and 36 per 100 000 for CD. Estimated rates adjusted to total population showed that IBD more than triplicated from 2008 to 2017. The distribution of IBD demonstrated a South-to-North gradient that generally followed population apportionment. However, marked regional differences and disease clusters were identified that did not fit with conventionally accepted IBD epidemiological associations, revealing that the rise of IBD was variable. In some areas, loss of biodiversity was associated with high IBD prevalence. CONCLUSIONS: When distribution is considered in the context of IBD prevalence, marked regional differences become evident. Despite a background of Westernization, hotspots of IBD are recognized that are not explained by population density, urbanicity, sanitation, or other indices but apparently are explained by biodiversity loss. Thus, the rise of IBD in developing countries is not uniform, but rather is one that varies depending on yet unexplored factors like geoecological conditions.

The analysis of a large population of inflammatory bowel disease (IBD) patients in a developing country reveals that the rising prevalence of IBD is not uniform and is linked to factors not traditionally associated with IBD, such as geosocial features and loss of biodiversity.

Abdominal ultrasonography with color Doppler analysis in the assessment of ileal Crohn's disease: comparison with magnetic resonance enterography.

BACKGROUND/AIMS: Consistently defining disease activity remains a critical challenge in the follow-up of patients with Crohn's disease (CD). We investigated the potential applicability of abdominal ultrasonography with color Doppler (USCD) analysis for the detection of morphological alterations and inflammatory activity in CD. METHODS: Forty-three patients with CD ileitis/ileocolitis were evaluated using USCD analysis with measurements obtained on the terminal ileum and right colon. Sonographic parameters included wall thickening, stricture, hyperemia, presence of intra-abdominal mass, and fistulas. Patients were evaluated for the clinical activity (Harvey-Bradshaw Index [HBI]), fecal calprotectin (FC) and C-reactive protein (CRP). The USCD performance was assessed using magnetic resonance enterography (MRE) as a criterion standard. RESULTS: Most measurements obtained with USCD matched the data generated with MRE; however, the agreement improved in clinically active patients where sensitivity, positive predictive value, and accuracy were >80%, considering wall thickening and hyperemia. Complications such as intestinal wall thickening, stricture formation, and hyperemia, were detected in the USCD analysis with moderate agreement with MRE. The best agreement with the USCD analysis was obtained in regard to FC, where the sensitivity, positive predictive value, and accuracy were >70%. The overall performance of USCD was superior to that of HBI, FC and CRP levels, particularly when considering thickening, stricture, and hyperemia parameters. CONCLUSIONS: USCD represents a practical noninvasive and low-cost tool for evaluating patients with ileal or ileocolonic disease, particularly in clinically active CD. Therefore, USCD might become a useful asset in the follow-up of patients with CD.

Ecological study of gastric cancer in Brazil: geographic and time trend analysis.

AIM: To investigate the geographic distributions and time trends of gastric cancer (GC) incidence and mortality in Brazil. METHODS: An ecological study of the DATASUS registry was conducted by identifying hospitalizations for GC between January 2005 and December 2010. The data included information on the gender, age, and town of residence at the time of hospital admission and death. RESULTS: The GC rates, adjusted according to available hospital beds, decreased from 13.8 per 100000 in 2005 to 12.7 per 100000 in 2010. The GC rates decreased more among the younger age groups, in which the male-to-female difference also decreased in comparison to the older age groups. Although the lethality rates tended to increase with age, young patients were proportionally more affected. The spatial GC distribution showed that the rates were higher in the south and southeast. However, while the rates decreased in the central-west and south, they increased in the northern regions. A geographic analysis showed higher rates of GC in more urbanized areas, with a coast-to-inland gradient. Geographically, GC lethality overlapped greatly with the hospital admission rates. CONCLUSION: The results of this study support the hypothesis of a critical role for environmental factors in GC pathogenesis. The declining rates in young patients, particularly males, suggest a relatively recent decrease in the exposure to risk factors associated with GC. The spatial distribution of GC indicates an ongoing dynamic change within the Brazilian environment.

Crohn's disease activity assessed by Doppler sonography: the role of aortic flow parameters.

OBJECTIVES: Intestinal neovascularization and abnormal abdominal arterial flow rates have been reported in Crohn's disease. The aim of this study was to evaluate Doppler sonography as a method for assessing Crohn's disease activity based on changes in splanchnic hemodynamics. METHODS: Forty-eight patients with Crohn's disease, 22 healthy volunteers and 12 patients with irritable bowel syndrome were evaluated by Doppler ultrasound for flow parameters of the aorta and superior mesenteric artery. This evaluation included the cross-sectional area, maximum flow volume, peak systolic velocity, end diastolic velocity, resistance and the pulsatility index. Disease activity was classified according to the Crohn's disease activity index. RESULTS: Most measurements in the aorta and superior mesenteric artery were significantly different between Crohn's disease patients and both control groups. Only the aortic maximum flow volume (CC = 0.37, p = 0.009) and aortic peak systolic velocity (CC = 0.30, p = 0.035) showed a significant positive correlation with the Crohn's disease activity index. The determination of cut-off points for the aortic maximum flow volume and peak systolic velocity measurements increased the sensitivity (80 and 75% for flow volume and velocity, respectively), specificity (57 and 75%), accuracy (67 and 75%) and positive (57 and 68%) and negative (80 and 81%) predictive values. These cut-off values permitted the correct classification of most of the patients with Crohn's disease with respect to disease activity. None of the superior mesenteric artery measurements were able to discriminate patients in relation to disease activity. CONCLUSION: The aortic maximum flow volume and peak systolic velocity levels estimated by Doppler sonography reflected disease activity in Crohn's disease. Doppler sonography of the aorta is therefore a novel noninvasive adjunct method that may be useful in the clinical follow-up of patients with Crohn's disease.

Crohn's disease activity assessed by doppler sonography: the role of aortic flow parameters

OBJECTIVES: Intestinal neovascularization and abnormal abdominal arterial flow rates have been reported in Crohn's disease. The aim of this study was to evaluate Doppler sonography as a method for assessing Crohn's disease activity based on changes in splanchnic hemodynamics. METHODS: Forty-eight patients with Crohn's disease, 22 healthy volunteers and 12 patients with irritable bowel syndrome were evaluated by Doppler ultrasound for flow parameters of the aorta and superior mesenteric artery. This evaluation included the cross-sectional area, maximum flow volume, peak systolic velocity, end diastolic velocity, resistance and the pulsatility index. Disease activity was classified according to the Crohn's disease activity index. RESULTS: Most measurements in the aorta and superior mesenteric artery were significantly different between Crohn's disease patients and both control groups. Only the aortic maximum flow volume (CC = 0.37, p = 0.009) and aortic peak systolic velocity (CC = 0.30, p = 0.035) showed a significant positive correlation with the Crohn's disease activity index. The determination of cut-off points for the aortic maximum flow volume and peak systolic velocity measurements increased the sensitivity (80 and 75% for flow volume and velocity, respectively), specificity (57 and 75%), accuracy (67 and 75%) and positive (57 and 68%) and negative (80 and 81%) predictive values. These cut-off values permitted the correct classification of most of the patients with Crohn's disease with respect to disease activity. None of the superior mesenteric artery measurements were able to discriminate patients in relation to disease activity. CONCLUSION: The aortic maximum flow volume and peak systolic velocity levels estimated by Doppler sonography reflected disease activity in Crohn's disease. Doppler sonography of the aorta is therefore a novel noninvasive adjunct method that may be ...

Hedgehog pathway signaling regulates human colon carcinoma HT-29 epithelial cell line apoptosis and cytokine secretion.

The Hedgehog (Hh) pathway is involved in embryogenesis and physiologic processes including cell survival and proliferation. We used the HT-29 and other human colon carcinoma cell lines to investigate Hh signaling and biological functions in colonic epithelial cells. HT-29 cells were cultured under different conditions and exposed to various stimuli. The expression of Hh pathway components and related genes and proteins were assessed by real-time PCR and immunofluorescence. Viability, apoptosis and cell proliferation were measured by the MTT assay, Annexin-V/7-AAD staining and BrdU uptake, respectively. Chemokines production was measured by ELISA in culture supernatants. Indian and Sonic Hh mRNA levels and the downstream transcription factors Gli-1 and Gli-2 increased following treatment with Hh agonists and butyrate, but decreased upon exposure to cyclopamine or GANT61. BMP4 and BMP7 expression increased after stimulation with Hh agonists. Gli-1 protein expression increased after Hh agonists and decreased following cyclopamine. Exposure to Hh agonists promoted ß-catenin reduction and subcellular redistribution. Levels of IL-8 and MCP-1 decreased upon exposure to Hh agonists compared to Hh antagonists, LPS, IFN-γ or EGF. Monocyte chemotaxis decreased upon exposure to supernatants of HT-29 cells treated with Shh compared to Hh antagonists, LPS and IFN-γ. Cellular incorporation of BrdU and cell viability decreased following Hh blockade. Hh agonists abrogated the anti-CD95 induced apoptosis. Hh pathway is a key controller of colon cancer cells, as demonstrated by its effect in dampening inflammatory signals and antagonizing apoptosis. The differential expression of Hh components may underlie abnormalities in the local immune response and in epithelial barrier integrity, with potential homeostatic implications for the development of colonic inflammation and malignancies.

Intraperitoneal but not intravenous cryopreserved mesenchymal stromal cells home to the inflamed colon and ameliorate experimental colitis.

BACKGROUND AND AIMS: Mesenchymal stromal cells (MSCs) were shown to have immunomodulatory activity and have been applied for treating immune-mediated disorders. We compared the homing and therapeutic action of cryopreserved subcutaneous adipose tissue (AT-MSCs) and bone marrow-derived mesenchymal stromal cells (BM-MSCs) in rats with trinitrobenzene sulfonic acid (TNBS)-induced colitis. METHODS: After colonoscopic detection of inflammation AT-MSCs or BM-MSCs were injected intraperitoneally. Colonoscopic and histologic scores were obtained. Density of collagen fibres and apoptotic rates were evaluated. Cytokine levels were measured in supernatants of colon explants. For cell migration studies MSCs and skin fibroblasts were labelled with Tc-99m or CM-DiI and injected intraperitonealy or intravenously. RESULTS: Intraperitoneal injection of AT-MSCs or BM-MSCs reduced the endoscopic and histopathologic severity of colitis, the collagen deposition, and the epithelial apoptosis. Levels of TNF-α and interleukin-1ß decreased, while VEGF and TGF-ß did not change following cell-therapy. Scintigraphy showed that MSCs migrated towards the inflamed colon and the uptake increased from 0.5 to 24 h. Tc-99m-MSCs injected intravenously distributed into various organs, but not the colon. Cm-DiI-positive MSCs were detected throughout the colon wall 72 h after inoculation, predominantly in the submucosa and muscular layer of inflamed areas. CONCLUSIONS: Intraperitoneally injected cryopreserved MSCs home to and engraft into the inflamed colon and ameliorate TNBS-colitis.

Prognostic significance of p53 protein expression in early gastric cancer.

Mutations of the p53 tumor suppressor gene have been associated with abnormalities in cell cycle regulation, DNA repair and synthesis, apoptosis, and it has been implicated in the prognosis of advanced gastric cancer. The aim of this study was to evaluate the occurrence of p53 gene mutation and its possible prognostic implications in early gastric cancer. In a retrospective study, we studied 80 patients with early gastric cancer treated surgically between 1982 and 2001. Mutation of p53 gene was investigated in surgical gastric specimens by immunohistochemistry, and results were analyzed in relation to gender, age, macroscopic appearance, size and location of tumor, presence of lymph nodes, Lauren's histological type, degree of differentiation, and the 5-year survival. The expression of p53 was more frequent among the intestinal type (p = 0.003), the differentiated (p = 0.007), and the macroscopically elevated tumors (p = 0.038). Nevertheless, the isolated expression of p53 was not associated with the 5-year survival, or with the frequency of lymph node involvement. The degree of differentiation was detected as an independent factor related to the outcome of patients (0.044). Significantly shorter survival time was found in p53-negative compared with p53-positive patients, when considering the degree of differentiation of tumors, as assessed by Cox regression analysis (0.049). The association of p53 with the intestinal type, the degree of differentiation and morphological characteristics, may reflect the involvement of chronic inflammatory process underlying early gastric cancer. In this population sample, the expression of p53 alone has no prognostic value for early gastric cancer. However, the significant difference in p53 expression between subgroups of degree of differentiation of tumors can influence post-operative outcome of patients and may be related to possible distinct etiopathogenic subtypes.

Unfractionated heparin and new heparin analogues from ascidians (chordate-tunicate) ameliorate colitis in rats.

The anti-inflammatory effect of mammalian heparin analogues, named dermatan sulfate and heparin, isolated from the ascidian Styela plicata was accessed in a TNBS-induced colitis model in rats. Subcutaneous administration of the invertebrate compounds during a 7-day period drastically reduced inflammation as observed by the normalization of the macroscopic and histological characteristics of the colon. At the molecular level, a decrease in the production of TNF-alpha, TGF-beta, and VEGF was observed, as well as a reduction of NF-kappaB and MAPK kinase activation. At the cellular level, the heparin analogues attenuated lymphocyte and macrophage recruitment and epithelial cell apoptosis. A drastic reduction in collagen-mediated fibrosis was also observed. No hemorrhagic events were observed after glycan treatment. These results strongly indicate the potential therapeutic use of these compounds for the treatment of colonic inflammation with a lower risk of hemorrhage when compared with mammalian heparin.

Pesquisa / Search

Dando continuidade ao relato da história da Faculdade de Medicina da UFRJ o artigo apresenta os primórdios e a institucionalização da ciência no Brasil, a pesquisa na Faculdade de Medicina da UFRJ, a pós-graduação e o incremento da pesquisa na faculdade, a pesquisa clínica na faculdade, os comitês de ética em pesquisa e a divulgação.

Análise descritiva dos perfis social, clínico, laboratorial e antropométrico de pacientes com doenças inflamatórias intestinais, internados no Hospital Universitário Clementino Fraga Filho, Rio de Janeiro / Descriptive analysis of the social, clinical, laboratorial and anthropometric profiles of inflammatory bowel disease inwards patients from the Clementino Fraga Filho University Hospital, Rio de Janeiro, RJ, Brazil

RACIONAL: Estudos epidemiológicos sobre doenças inflamatórias intestinais no Brasil são limitados devido a dificuldades diagnósticas e reduzidas amostras populacionais estudadas. A maioria dos estudos de sua prevalência disponível é composta por amostras de pacientes sob acompanhamento em ambulatório, entretanto a análise do perfil de pacientes com doenças inflamatórias intestinais hospitalizados pode auxiliar na detecção de marcadores preditivos de sua gravidade, o que permitirá intervenções médicas precoces visando a redução da taxa de hospitalização e os gastos do sistema de saúde. OBJETIVOS: Descrever o perfil social, clínico, laboratorial e antropométrico dos pacientes adultos com doenças inflamatórias intestinais internados em hospital universitário terciário. MÉTODOS: Estudo prospectivo com 43 pacientes com doenças inflamatórias intestinais internados nas enfermarias clínicas e cirúrgicas e no setor de emergência do Hospital Universitário Clementino Fraga Filho da Universidade Federal do Rio de Janeiro, RJ. Foram caracterizados dados demográficos, presença de co-morbidades, localização e comportamento clínico, história cirúrgica, manifestações extra-intestinais utilizando-se definições padronizadas. Os resultados laboratoriais foram verificados nos prontuários e as medidas antropométricas foram realizadas durante a entrevista. RESULTADOS: A maioria dos pacientes apresentou doença de Crohn (72,1 por cento), com localização íleo-colônica (60 por cento) e com comportamento penetrante (77,4 por cento), enquanto no grupo retocolite ulcerativa idiopática predominou a pancolite (50 por cento). No grupo total de retocolite ulcerativa idiopática, a artralgia foi a manifestação extra-intestinal mais freqüente (44,2 por cento) e 97,7 por cento já havia apresentado algum tipo de complicação relacionada à doença de base. Apesar do uso de terapêutica específica para doenças inflamatórias intestinais prévio à hospitalização em 79,1 por cento...

BACKGROUND: The epidemiologic survey in Brazil is limited probably due to a diagnosis deficiency and a small number of population-based studies performed. The majority of the prevalence studies available have evaluated inflammatory bowel diseases outpatients, but the knowledge of the profile of inflammatory bowel diseases inpatients is important in order to detect predictive markers of disease severity that will allow earlier medical intervention decreasing the rate of hospitalization and reducing the Health System costs. AIM: To determine social, clinical, laboratorial and anthropometric profiles of hospitalized adults inflammatory bowel diseases patients of a tertiary university hospital. METHODS: Prospective study was performed with 43 inflammatory bowel diseases inpatients from clinical and surgical wards and emergency section of university hospital. We characterized demographic data, presence of comorbidities, disease location and behavior, surgical past-history, extra intestinal manifestations using standardized definitions. Laboratory results were abstracted from medical records and anthropometric measures were performed during our visit. RESULTS: The vast majority of the inflammatory bowel diseases patients had Crohn's disease (72.1 percent), with ileocolic involvement (60 percent), with a penetrating disease behavior (77.4 percent) while ulcerative colitis group presented mostly pancolitis (50 percent). Articular pain was the most common (44.2 percent) extra intestinal manifestation of inflammatory bowel diseases patients and 97.7 percent of them had at least one type of complication related to disease. Although, the previous use of specific medical therapies to inflammatory bowel diseases before the hospitalization (more frequently corticosteroids) was done (79 percent), the majority of the patients were hospitalized because of inflammatory bowel diseases activity. Disease activity was present in 80.7 percent of Crohn's disease...

Therapeutic and prophylactic thalidomide in TNBS-induced colitis: synergistic effects on TNF-alpha, IL-12 and VEGF production.

AIM: To evaluated the therapeutic and prophylactic effect of thalidomide on 2, 4, 6-trinitrobenzene sulfonic acid (TNBS)-induced colitis. Thalidomide has been reported to downregulate the expression of tumor necrosis factor alpha (TNF-alpha), IL-12, and vascular endothelial growth factor (VEGF), hallmarks of intestinal inflammation in Crohnos disease (CD). METHODS: Male Wistar rats were divided in five groups of ten animals each. Four groups received a rectal infusion of TNBS in ethanol. The first group was sacrificed 7 d after colitis induction. The second and third groups received either thalidomide or placebo by gavage and were sacrificed at 14 d. The fourth group received thalidomide 6 h before TNBS administration, and was sacrificed 7 d after induction. The fifth group acted as the control group and colitis was not induced. Histological inflammatory scores of the colon were performed and lamina propria CD4+ T cells, macrophages, and VEGF+ cells were detected by immunohistochemistry. TNF-alpha and IL-12 were quantified in the supernatant of organ cultures by ELISA. RESULTS: Significant reduction in the inflammatory score and in the percentage of VEGF+ cells was observed in the group treated with thalidomide compared with animals not treated with thalidomide. Both TNF-alpha and IL-12 levels were significantly reduced among TNBS induced colitis animals treated with thalidomide compared with animals that did not receive thalidomide. TNF-alpha levels were also significantly reduced among the animals receiving thalidomide prophylaxis compared with untreated animals with TNBS-induced colitis. Intestinal levels of TNF-alpha and IL-12 were significantly correlated with the inflammatory score and the number of VEGF+ cells. CONCLUSION: Thalidomide significantly attenuates TNBS-induced colitis by inhibiting the intestinal production of TNF-alpha, IL-12, and VEGF. This effect may support the use of thalidomide as an alternate approach in selected patients with CD.

[Descriptive analysis of the social, clinical, laboratorial and anthropometric profiles of inflammatory bowel disease inwards patients from the "Clementino Fraga Filho" University Hospital, Rio de Janeiro, RJ, Brazil]. / Análise descritiva dos perfis social, clínico, laboratorial e antropométrico de pacientes com doenças inflamatórias intestinais, internados no Hospital Universitário Clementino Fraga Filho, Rio de Janeiro.

BACKGROUND: The epidemiologic survey in Brazil is limited probably due to a diagnosis deficiency and a small number of population-based studies performed. The majority of the prevalence studies available have evaluated inflammatory bowel diseases outpatients, but the knowledge of the profile of inflammatory bowel diseases inpatients is important in order to detect predictive markers of disease severity that will allow earlier medical intervention decreasing the rate of hospitalization and reducing the Health System costs. AIM: To determine social, clinical, laboratorial and anthropometric profiles of hospitalized adults inflammatory bowel diseases patients of a tertiary university hospital. METHODS: Prospective study was performed with 43 inflammatory bowel diseases inpatients from clinical and surgical wards and emergency section of university hospital. We characterized demographic data, presence of comorbidities, disease location and behavior, surgical past-history, extra intestinal manifestations using standardized definitions. Laboratory results were abstracted from medical records and anthropometric measures were performed during our visit. RESULTS: The vast majority of the inflammatory bowel diseases patients had Crohn's disease (72.1%), with ileocolic involvement (60%), with a penetrating disease behavior (77.4%) while ulcerative colitis group presented mostly pancolitis (50%). Articular pain was the most common (44.2%) extra intestinal manifestation of inflammatory bowel diseases patients and 97.7% of them had at least one type of complication related to disease. Although, the previous use of specific medical therapies to inflammatory bowel diseases before the hospitalization (more frequently corticosteroids) was done (79%), the majority of the patients were hospitalized because of inflammatory bowel diseases activity. Disease activity was present in 80.7% of Crohn's disease and 50% ulcerative colitis patients. Inflammatory bowel diseases mortality rate was 5.5% (2/36). Comorbidities presence occurred only in 30.2% of inflammatory bowel diseases patients. The predominant surgery performed was intestinal resection. The interval between the symptoms appearance and the definitive diagnosis was less than 1 year in more than 70% of inflammatory bowel diseases patients. Laboratory findings detected were a decreased serum albumin (85.7%) and anemia (69.8%). The majority of the patients had at least one anthropometric alteration. The social stratification of the inflammatory bowel diseases group was similar to the Brazilian population. CONCLUSION: The inflammatory bowel diseases inpatients from the university hospital wards had more severe evolution of these illnesses with an active and extensive disease with complications and frequent extra intestinal manifestations, despite the prolonged use of corticosteroids. The higher prevalence of Crohn's disease inpatients than ulcerative colitis could reflect a higher aggressive behavior of this disease. The reduced serum albumin, anemia and anthropometric alterations are common inflammatory bowel diseases inpatients and could be related to a major severity of inflammatory bowel diseases evolution.

Distinct patterns of mucosal apoptosis in H pylori-associated gastric ulcer are associated with altered FasL and perforin cytotoxic pathways.

AIM: To analyze the level of apoptosis in different mucosal compartments and the differential expression of Fas/Fas-ligand and perforin in H pylori-associated gastric ulcer. METHODS: Antral specimens from patients with H pylori-related active gastric ulcer (GU), H pylori-related gastritis, and non-infected controls were analysed for densities and distribution of apoptotic cells determined by the TdT-mediated dUDP-biotin nick-end-labelling method. GU patients were submitted to eradication therapy with follow-up biopsy after 60 d. Fas, FasL, and perforin-expressing cells were assessed by immunoperoxidase, and with anti-CD3, anti-CD20 and anti-CD68 by double immunofluorescence and confocal microscopy. Quantitative analysis was performed using a computer-assisted image analyser. RESULTS: H pylori-infected antrum showed greater surface epithelial apoptosis which decreased after eradication therapy. In the lamina propria, higher rates of mononuclear cell apoptosis were observed in H pylori-gastritis. Co-expression of Fas with T-cell and macrophage markers was reduced in GU. FasL- and perforin-expressing cells were increased in H pylori-infection and correlated with epithelial apoptosis. Perforin-expressing cells were also increased in GU compared with H pylori-gastritis. CONCLUSION: Epithelial apoptosis is increased in H pylori-infection and correlates to FasL- and perforin-expression by T cells. Expression of perforin is correlated with the tissue damage, and may represent the enhancement of a distinct cytotoxic pathway in GU. Increased expression of FasL not paralleled by Fas on T-cells and macrophages may indicate a reduced susceptibility to the Fas/FasL-mediated apoptosis of lymphoid cells in H pylori-infection.

Prevalence of hepatitis C virus and evaluation of associated risk factors in a group of Braziliam patients with inflammatory bowel disease

Objective: To evaluate the prevalence of the hepatitis C virus (HCV) infection and associated risk factors in patients with inflammatory bowel disease followed at the University Hospital Clementino Fraga Filho, Federal University of Rio de Janeiro (HUCFF-UFRJ). Methods: A total of 146 patients were studied, 58 with Crohn's disease and 88 with ulcerative colitis, with a mean age of 40 years. The results were correlated with the following variables: time elapsed since diagnosis, endoscopic exams, surgeries, use of intravenous drugs, blood transfusion and immunosuppressor therapy. Results: The prevalence of anti-HCV was 4,8por cento(7/146). Both univariate and multivariate analysis showed blood transfusion as the only risk factor significantly associated with HCV infection (rr= 5.71; 95por cento confidence interval: 1.04-10.37; p= 0.023). Conclusion: The prevalence of HCV infection in patients with inflammatory bowel disease was higher thanthat observed among blood donors of the same region and the only risk factor associated with this infection was blood transfusion

Biochemical and immunohistochemical analysis of glycosaminoglycans in inflamed and non-inflamed intestinal mucosa of patients with Crohn's disease.

OBJECTIVES: Changes in extracellular matrix glycosaminoglycans (GAGs) of the intestinal mucosa have been associated with inflammatory bowel disease. The aim of the present study was to follow the changes in GAGs metabolism during the progression from non-inflamed to inflamed intestinal colon of patients with Crohn's disease (CD), using direct biochemical analysis and specific immunohistochemistry against chondroitin/dermatan sulfate and heparan sulfate. DESIGN AND METHODS: The content of GAGs from inflamed and non-inflamed colon of eight patients with active CD was estimated by uronic acid per dry weight of tissue and analyzed by agarose gel electrophoresis and ion-exchange chromatography. Intestinal sections were stained using antibodies against dermatan sulfate/chondroitin 4-sulfate (DS/CS), heparan sulfate (HS), and ICAM-1 (CD54), and analyzed by confocal microscopy. RESULTS: There was a reduction in the amount of GAGs in the non-inflamed colon of patients with CD. In the inflamed colon, HS, CS and DS showed increased concentrations compared with the non-inflamed colon. GAGs showed a diffuse distribution in the lamina propria and in the basement membrane of both inflamed and non-inflamed mucosa of patients with CD. CONCLUSION: We observed a marked reduction in GAGs with altered patterns of distribution in the non-inflamed colon of patients with CD. The increase in the synthesis of GAGs observed in the inflamed colon may be a compensatory mechanism for the restoration of the integrity of the intestinal mucosa.

Apoptosis in the intestinal mucosa of patients with inflammatory bowel disease: evidence of altered expression of FasL and perforin cytotoxic pathways.

BACKGROUND AND AIMS: Abnormal apoptosis may result in the persistence of activated intestinal T-cells in inflammatory bowel disease (IBD). We investigated apoptosis in distinct mucosal compartments, and the expression of Fas/Fas ligand and perforin in the inflamed and non-inflamed intestinal mucosa of patients with IBD. METHODS: Colon specimens from 15 patients with ulcerative colitis (UC) and inflamed and non-inflamed mucosa from 15 patients with Crohn's disease (CD) were analysed for densities and distribution of apoptotic cells determined by the terminal deoxynucleotidyltransferase-mediated dUDP-biotin nick-end labelling (TUNEL) method. Fas, FasL, and perforin-expressing cells were assessed by immunoperoxidase, and with anti-CD3, anti-CD20 and anti-CD68, by double immunofluorescence with confocal microscopy. Quantitative analysis was performed using a computer-assisted image analyser. RESULTS: Colonic lamina propria (LP) and epithelium from patients with UC showed higher rates of apoptosis than controls, but no difference was shown regarding patients with CD. In LP, co-expression of Fas was reduced with T-cells in inflamed CD mucosa, and with macrophages in all patients with IBD. No difference was found in the expression of Fas on B-cells. Rates of FasL-expressing cells in LP were higher in IBD than in controls, with no correlation with the rates of apoptosis. Rates of perforin-expressing cells in LP were greater in UC than in controls, and correlated to the rates of apoptosis. No difference was shown regarding the inflamed and non-inflamed CD mucosa. Rates of FasL and perforin-expressing intra-epithelial lymphocytes showed no difference among groups. CONCLUSIONS: Increased expression of FasL in IBD colonic LP not parallelled by Fas on T-cells and macrophages may indicate a reduced susceptibility to the Fas/FasL-mediated apoptosis of lymphoid cells. Expression of perforin is correlated to the tissue damage, and may represent the enhancement of a distinct cytotoxic pathway in UC.

Small bowel of patients with asthma and allergic rhinitis: absence of inflammation despite the presence of major cellular components of allergic inflammation.

Eosinophils participate in the pathogenesis of inflammatory diseases of the respiratory tract and the gut. We investigated the constitutive presence of eosinophils and mononuclear cells in the macroscopically normal duodenal mucosa of patients with asthma and allergic rhinitis. Macroscopically normal duodenal specimens were obtained at routine endoscopy for upper gastrointestinal symptoms from 16 patients with asthma and 13 patients with allergic rhinitis. Twelve nonatopic patients with irritable bowel syndrome were studied as controls. Specimens were analyzed by immunohistochemistry using a panel of antibodies to human eosinophil cationic protein clone EG1 (EG1) and clone EG2 (EG2), anti-human interleukin (anti-hIL)-5, anti-hIL-4, anti-CD4, and anti-CD68. Significantly increased numbers of eosinophils stained with EG1 and EG2 were found in the duodenum of patients with asthma and allergic rhinitis compared with controls. IL-5+ cells and IL-4+ cells were detected in significantly increased numbers in the duodenal mucosa of patients with asthma and rhinitis compared with controls. Mononuclear cells expressing CD4 (helper T cells) and CD68 (macrophages) also were significantly increased in the duodenal mucosa of asthma and rhinitis compared with controls. Accumulation of eosinophils in conjunction with IL-4+ cells and IL-5+ cells in the noninflamed duodenal mucosa may reflect a predominant T helper cell subset 2 systemic immune response in patients with asthma and allergic rhinitis. The absence of intestinal inflammation despite the marked presence of cells implicated in the allergic inflammation suggests that local mechanisms might determine the state of nonresponsiveness in the gut mucosa of patients with asthma and allergic rhinitis.

Effects of ethanol on gut-associated lymphoid tissues in a model of bacterial translocation: a possible role of apoptosis.

Chronic ethanol intake has been shown to be associated with immune suppression and impairment of epithelial barrier function. We investigated the effects of ethanol on intestinal immunity and its relation to bacterial translocation (BT). Male Wistar rats were assigned to one of three groups and received respective diets for 28 days. The ethanol-fed group [(EG); n=11] received a liquid diet containing 5% [volume/volume (vol./vol.)] ethanol; a pair-fed group [(PFG); n=11] received an isocaloric diet without ethanol; and a third (control) group [(CG); n=11] received water and chow ad libitum. On experimental day 29, animals in the EG and the PFG underwent distal ileum ligature and small intestine inoculation of a tetracycline-resistant Escherichia coli strain (TcR E. coli R6), by means of gastric intubation, followed by duodenal ligature. One hour after inoculation, mesenteric lymph nodes, right lobe of liver, spleen, and left kidney were excised for bacterial studies. Sections of jejunum and colon were immunostained, with the use of antibodies against immunoglobulin (Ig) A, T cells, macrophages, and proliferating cell nuclear antigen (PCNA). Apoptosis was determined by the terminal deoxynucleotidyltransferase TdT-mediated dUDP-biotin nick end labeling (TUNEL) method. Bacterial translocation rates were greater in the PFG compared with findings for the EG. Lamina propria of the jejunum of the EG showed a reduction in the densities of IgA+ cells and T cells compared with findings for the PFG and the CG. Colonic lamina propria of the EG showed reduced densities of IgA+ cells and macrophages compared with findings for the PFG and the CG. Apoptotic index was increased in the EG compared with findings for the PFG and the CG, in both jejunum and colon. Proliferation index was not significantly different among groups. Results of the current study show that chronic ethanol ingestion led to a reduction of cellular and humoral components of the intestinal mucosa, possibly by cell loss as a result of ethanol-induced apoptosis. The reduced rates of BT observed after chronic ethanol intake seem to indicate that factors irrespective of immune function might be involved in BT inhibition.

Intestinal T-cell lymphoma with and without celiac disease: report of two cases

Os autores relatam dois casos de linfoma intestinal de células T, um dos quais associado a doença celíaca. Os dois pacientes desenvolveram sintomas abdominais agudos e a laparotomia revelou perfuração de jejuno. Foi realizada uma ressecção parcial do jejuno e o exame revelou ulcerações intestinais multiplas e linfoma intestinal de células T. O prognóstico desses pacientes não foi bom por ser tardio o diagnóstico e pelo baixo desempenho por ocasião da apresentação