Although with intact mucosa at colonoscopy, chagasic megacolons have an overexpression of Gal-3 / Embora com mucosa íntegra à colonoscopia, megacólons chagásicos apresentam superexpressão de Gal-3

ABSTRACT Objective To evaluate the density of anti-galectin-3-immunostained cells, collagen percentage, mast cell density and presence of pathological processes in intestinal muscle biopsies of patients. Methods Thirty-five patients who underwent intestinal biopsy were selected from 1997 to 2015. Patients were divided into three groups: chagasic patients with mucosal lesion (n=13), chagasic patients with intact mucosa (n=12) and non-chagasic patients with no mucosal lesion (n=10). Histological processing of the biopsied fragments and immunohistochemistry for galectin-3 were performed. Additional sections were stained with hematoxylin and eosin to evaluate the general pathological processes, picrosirius for evaluation of collagen and toluidine blue to evaluate the mast cell density. Results Patients of mucosal lesion group had a significantly higher frequency of ganglionitis and myositis when compared to the chagasic patients with intact mucosa and non-chagasic group. The density of anti-galectin-3-immunostained cells was significantly higher in the chagasic patients with intact mucosa group when compared to the non-chagasic group. The group of chagasic patients with intact mucosa presented a higher percentage of collagen in relation to the patients with mucosal lesion and to the non-chagasic group, with a significant difference. There was no significant difference in mast cell density among the three groups. Conclusion The higher density of anti-galectin-3-immunostained cells in patients in the chagasic patients with intact mucosa group suggested the need for greater attention in clinical evaluation of these patients, since this protein is associated with neoplastic transformation and progression.

RESUMO Objetivo Avaliar a densidade de células imunomarcadas por anti-galectina-3, a percentagem de colágeno, a densidade de mastócitos e a presença de processos patológicos na musculatura intestinal de pacientes biopsiados. Métodos Foram selecionados 35 pacientes submetidos à biópsia de intestino entre 1997 a 2015. Os pacientes foram divididos em três grupos: chagásicos com lesão de mucosa (n=13), chagásicos com mucosa íntegra (n=12) e não chagásicos sem lesão de mucosa (n=10). Foram realizados processamento histológico dos fragmentos biopsiados e imunohistoquímica para galectina-3. Cortes adicionais foram corados por hematoxilina e eosina, para avaliar os processos patológicos gerais, pelo picrosírius, para avaliação do colágeno, e pelo azul de toluidina, para avaliar a densidade de mastócitos. Resultados Os pacientes do grupo chagásicos com lesão de mucosa apresentaram frequência significativamente maior de ganglionite e miosite quando comparados aos dos grupos chagásico com mucosa íntegra e não chagásicos. A densidade das células imunomarcadas por anti-galectina-3 foi significativamente maior no grupo chagásicos com mucosa íntegra quando comparada ao grupo não chagásico. O grupo de chagásicos com mucosa íntegra apresentou maior percentagem de colágeno em relação aos grupos chagásicos com mucosa lesada e ao grupo de não chagásicos, com diferença significativa. Não houve diferença significativa com relação à densidade de mastócitos entre os três grupos. Conclusão A maior densidade de células imunomarcadas por anti-galectina-3 nos pacientes do grupo chagásico com mucosa íntegra sugere a necessidade de maior atenção na avaliação clínica desses pacientes, uma vez que essa proteína está associada com transformação e progressão neoplásica.

Effects of anti-TNF-α in experimental diversion colitis

Abstract Purpose: To evaluate the effects of infliximab on the inflammation of the colonic mucosa devoid from fecal stream. Methods: Twenty-four rats were submitted to a Hartmann's procedure. They remained for 12 weeks with the fecal derivation to development of diversion colitis on excluded colorectal stump. After this period, they were divided into 3 groups: one group received intervention with saline (2.0 mL / week), other group infliximab at doses of 5 mg/kg/week and the other 10 mg/kg/week for five consecutively weeks. Concluded the intervention period, the animals were euthanized to remove colon segments with and without fecal stream. Colitis was diagnosed by histological analysis and the degree of inflammation by validated score. The neutrophilic infiltrate was evaluated by tissue expression of myeloperoxidase identified by immunohistochemical. The tissue content of myeloperoxidase was measured by computer-assisted image analysis. Results: The inflammatory score was high in colonic segments without fecal stream. The intervention with infliximab reduced the inflammatory score in excluded colonic segments. The content of myeloperoxidase was reduced in colonic segments of animals treated with infliximab mainly in high concentrations. Conclusion: Intervention with infliximab reduced the inflammation and the neutrophil infiltrate in colonic segments devoid of the fecal stream.

Histopathological and ultrastructural findings induced by heat-inactivated Lactobacillus plantarum and the culture supernatant on the intestinal mucosa of piglets: an ex vivo approach / Achados histopatológicos e ultraestruturais induzidos por Lactobacillus plantarum inativado pelo calor na mucosa intestinal de leitões: estudo ex-vivo

In the present study, histological, morphometrical and ultrastructural analysis were performed to investigate intestinal mucosa changes in piglets jejunal explants exposed to two concentration of heat-inactivated Lactobacillus plantarum and their respective culture supernatants. Jejunal explants were incubated for 4 hours in DMEM culture medium with a) only culture medium (control group), b) heat-inactivated Lactobacillus plantarum strain1 - LP1 (1.1 x 108CFU/ml), c) heat-inactivated Lactobacillus plantarum strain2 - LP2 (2.0 x 109CFU/ml), d) heat-inactivated Lactobacillus plantarum strain1 culture supernatant (CS1), and e) heat-inactivated Lactobacillus plantarum strain2 culture supernatant (CS2). Explants exposed to heat-inactivated L. plantarum strain 1 and 2 showed multifocal to difuse villi atrophy, villi apical necrosis and enterocyte flattening. Morphological assessment revealed similar results with bacterial adhesion to mucus and intestinal epithelial cells and, morphometric analysis showed a decreased villi height compared to the control group. Alterations in explants treated with the culture supernatant of both strains include mild villi atrophy and mild enterocyte apical necrosis. Morphological assesment reveled numerous well delineated villi and, morphometric analysis showed a significant increase in villi height compared to the control group. In general, exposure to the culture supernatants improved the intestinal morphology.(AU)

No presente estudo, foram realizadas análises histológica, morfométrica e ultraestrutural para investigar as alterações da mucosa intestinal em explantes jejunais de leitões expostos a duas cepas e concentrações de Lactobacillus plantarum inativado pelo calor e seus sobrenadantes de cultura. Os explantes jejunais foram incubados durante quatro horas, em meio de cultura DMEM com: a) meio de cultura (grupo controle); b) Lactobacillus plantarum, cepa 1 - LP1 (1,1 x 108CFU/mL); c) Lactobacillus plantarum, LP2 (2,0 x 109CFU/mL); d) sobrenadante da cultura do Lactobacillus plantarum, cepa 1 (SC1); e e) sobrenadante da cultura do Lactobacillus plantarum, cepa 2 (SC2). Os explantes expostos às cepas 1 e 2 do L. plantarum inativado pelo calor mostraram atrofia difusa de vilosidades, necrose apical das vilosidades e achatamento de enterócitos. A avaliação morfológica revelou resultados semelhantes, com adesão bacteriana ao muco e às células epiteliais intestinais, e a análise morfométrica mostrou uma diminuição da altura das vilosidades em relação ao grupo controle. Alterações nos explantes tratados com o sobrenadante da cultura de ambas as cepas caracterizaram-se por atrofia leve das vilosidades e necrose apical leve dos enterócitos. A avaliação morfológica revelou vilosidades bem delineadas, e a análise morfométrica mostrou um aumento significativo na altura das vilosidades em comparação ao grupo controle. Em geral, a exposição aos sobrenadantes da cultura melhora a morfologia intestinal.(AU)

Is the colon mucosa affected by ten days of gastric restriction in an animal model?

Abstract Purpose To identify whether the colon mucosa is affected by ten days of gastric restriction in an animal model. Methods An experimental model of gastric restriction was devised using rats. The animals were submitted to surgical gastrostomy, and a cylindrical loofah was inserted into the stomach. We studied 30 adult male Wistar rats divided into three groups: the stomach restriction group (R10); the sham group (S10), which underwent the same procedure except for the loofah insertion; and the control group (C10). The expression of neutral and acid mucins was evaluated using histochemical techniques. Goblet cells and protein content were compared between groups using generalized estimation equations (GEEs). Bonferroni's multiple comparison was applied to identify differences between the groups. All tests considered a 5% significance level. Results There was an increased expression of neutral mucins, acid mucins and goblet cells in the R10 group. Collagen was also enhanced in the R10 group. Conclusion The colon mucosa is affected by ten days of gastric restriction in an animal model, increasing neutral mucins, acid mucins and collagen content with trophic maintenance.

The effect of ileocecal valve removal in a model of short bowel syndrome / Efeito da remoção da válvula ileocecal em modelo de síndrome do intestino curto

ABSTRACT Background : Short bowel syndrome is a harmful condition that needs experimental research. Aim: To assess the impact of the ileocecal valve removal in a model of short bowel syndrome, in order to investigate the evolution of the colon under this circumstance. Method: Fifteen Wistar rats were equitable divided into: Control (Sham), Group I (70% enterectomy preserving ileocecal valve) and Group II (70% enterectomy excluding ileocecal valve). After enterectomy was performed jejunoileal or jejunocecal anastomosis and sacrificed the animals on 30th postoperative day for histomorphometric study of the colon. During this period, was observed the clinical evolution of the animals weekly including body weight measurement. Results: Group I and II presented progressive loss of weight. In Group I was observed diarrhea, perineal hyperemia and purple color of the colon during autopsy. Histomorphometry assay showed hypertrophy and hyperplasia of colon mucosa in Group I. In Group II the colon wall was thicker due to hypertrophy and muscular hyperplasia, and in mucosa vascular proliferation and inflammatory infiltrate were intense. Conclusion : This short bowel syndrome model is relevant and achieve 100% of survival. Animal's weight loss was not altered by the presence or exclusion of the ileocecal valve. Animals with 70% of small bowel removal and presence of the ileocecal valve attained a better clinical evolution and histological colon adaptation than those without ileocecal valve.

RESUMO Racional: Síndrome do intestino curto é condição clínica crítica e que precisa de pesquisa experimental. Objetivo: Avaliar o impacto da remoção da válvula ileocecal em um modelo de síndrome do intestino curto para investigar o comportamento do cólon nesta circunstância. Método: Quinze ratos Wistar foram divididos em três grupos de cinco: Controle (Sham), grupo I (enterectomia de 70% com preservação da válvula ileocecal), e grupo II (70% enterectomia de 70% excluindo a válvula ileocecal). Após a enterectomia foi restabelecido o trânsito com anastomose jejunoileal no grupo I e jejunocecal no grupo II. Os animais foram sacrificados no 30º dia do pós-operatório para histomorfometria do cólon. Durante este período, observou-se a evolução clínica semanal, incluindo a medição do peso corporal. Resultados: Grupos I e II apresentaram perda progressiva de peso. No grupo I houve diarreia, períneo hiperemiado e cor violácea do cólon durante a autópsia. A histomorfometria mostrou hipertrofia e hiperplasia da mucosa do cólon no grupo I. No grupo II a parede do cólon estava mais espessa devido à hipertrofia e hiperplasia das camadas muscular e mucosa onde a proliferação vascular e infiltração inflamatória foi intensa. Conclusão: Este modelo é factível e atingiu 100% de sobrevida. A perda de peso não foi alterada pela presença ou exclusão da válvula ileocecal. Animais com remoção de 70% do intestino delgado e presença da válvula ileocecal apresentaram melhor evolução clínica e adaptação histológica do cólon que os sem válvula ileocecal.

Effect of copaiba oil in intestinal mucosa of rats submitted to hypovolemic shock / Efeito do óleo de copaíba na mucosa intestinal de ratos submetidos ao choque hipovolêmico

ABSTRACT Background: Hypovolemic shock is a common disease in polytrauma patients and may develop ischemia in various organs, increasing morbidity and mortality. The bowel is usually most affected by this condition. Aim: To evaluate the effects of copaiba oil on the intestinal mucosa's injury of rats submitted to hypovolemic shock. Method: Fifteen rats were divided into three groups: sham - simulated surgery; ischemia - animals submitted to hypovolemic shock; and copaiba - animals submitted to hypovolemic shock previously treated with copaiba oil. Mean blood pressure, arterial blood gas after shock induction, degree of intestinal lesion and villus length were evaluated. Results: The sham presented the lowest values of lactate and PaCO2 and the highest values of mean arterial pressure, pH and bicarbonate in relation to the other groups. The degree of mesenteric lesion was zero in the sham group; 3.00±1.00 in the ischemia group; and 3.00±0.71 in the copaiba group. The villus length was 173.60±8.42 in the sham, 142.77±8.33 in the ischemia and 143.01±9.57 in the copaiba group. There was a significant difference between the sham and the other groups (p<0.05); however, there not significant difference between groups Ischemia and copaiba. Conclusion: Administration of copaiba oil did not reduce the intestinal mucosa lesion of rats after hypovolemic shock.

RESUMO Racional: O choque hipovolêmico é situação comum em pacientes politraumatizados, podendo acarretar isquemia de vários órgãos, aumentando a morbimortalidade. O intestino é geralmente um dos órgãos mais afetados por essa condição. Objetivo: Avaliar os efeitos do óleo de copaíba na lesão da mucosa intestinal de ratos submetidos ao choque hipovolêmico. Métodos: Quinze ratos foram distribuídos em três grupos: Sham - operação simulada; isquemia - submissão ao choque hipovolêmico; e copaíba - submissão ao choque hipovolêmico previamente tratados com óleo de copaíba. A pressão arterial média, a gasometria arterial após a indução do choque, o grau da lesão intestinal e o tamanho das vilosidades foram avaliados. Resultados: O grupo sham apresentou os menores valores de lactato e PaCO2 e os maiores valores de pressão arterial média, pH e bicarbonato em relação aos demais grupos. O grau de lesão mesentérica foi de zero no sham; 3,0±1,00 no grupo isquemia; e 3,0±0,71 no da copaíba. O comprimento dos vilos foi de 173,60±8,42 no grupo sham, 142,77±8,33 no da isquemia e 143,01±9,57 no da copaíba. Houve diferença significante entre o grupo sham e os demais grupos (p<0.05); contudo, não houve diferença estatística entre os grupos submetidos ao choque hipovolêmico. Conclusão: A administração do óleo de copaíba não reduziu a lesão da mucosa intestinal de ratos submetidos ao choque hipovolêmico.

Oxidative stress assessment in intestine of newborn rats submitted to hypoxia and reoxygenation with tadalafil

Abstract Purpose: To evaluate the functional and structural response of tadalafil effects in the intestinal mucosa, using an experimental model of hypoxia and reoxygenation injury in rats. Methods: The animals were divided into 4 groups: CTL, H/R, H/R+Td and M+Td. The newborn rats allocated in groups H/R, H/R+Td and M+Td were submitted twice a day, to a gas chamber with CO2 at 100% for 10 minutes and afterward reoxygenation with O2 at 98% for 10 minutes, in the three first days of life. Tadalafil dose was given to newborn of group H/R+Td and to the pregnant rat of group M+Td. Histological analysis was made with hematoxylin-eosin technique and oxidative stress through nitrite and nitrate levels and lipid peroxidation. Results: The histological analysis showed a reduction of mucosa alterations in the groups that received tadalafil. In the oxidative stress evaluation, occurred an increase of NO levels and less lipidic peroxidation in the ileum segments that received tadalafil. Conclusion: Tadalafil provides tissue protection when administered independently to both, pregnant or newborns.

Enemas with mesalazine increase the tissue contents of mucins in the colonic mucosa devoid of fecal stream

Abstract Purpose: To evaluate the inflammatory reaction and measure the content of mucins, in the colonic mucosa without fecal stream submit to intervention with mesalazine. Methods: Twenty-four rats were submitted to a left colostomy and a distal mucous fistula and divided into two groups according to euthanasia to be performed two or four weeks. Each group was divided into two subgroups according daily application of enemas containing saline or mesalazine at 1.0 g/kg/day. Colitis was diagnosed by histological analysis and the inflammatory reaction by validated score. Acidic mucins and neutral mucins were determined with the alcian-blue and periodic acid of Schiff techniques, respectively. Sulfomucin and sialomucin were identified by high iron diamine-alcian blue technique. The tissue contents of mucins were quantified by computer-assisted image analysis. Mann-Whitney test was used to analyze the results establishing the level of significance of 5%. Results: Enemas with mesalazine in colonic segments without fecal stream decreased the inflammation score and increased the tissue content of all subtypes of mucins. The increase of tissue content of neutral, acid and sulfomucin was related to the time of intervention. Conclusion: Mesalazine enemas reduce the inflammatory process and preserve the content of mucins in colonic mucosa devoid of fecal stream.

Neutrophils, eosinophils, and mast cells in the intestinal wall of dogs naturally infected with Leishmania infantum / Neutrófilos, eosinófilos e mastócitos na parede intestinal de cães naturalmente infectados com Leishmania infantum

Abstract Visceral leishmaniasis (VL) is a disease caused by the protozoa Leishmania infantum and can cause an inflammatory reaction in the gastrointestinal tract, however the role of granulocytic cells (neutrophils, eosinophils, and mast cells) in the intestine of dogs infected is not fully understood. We performed a quantitative analysis these cells in the intestinal wall of dogs with canine visceral leishmaniasis (CVL). Twenty dogs were assigned to one of three groups: group 1 (G1, n=8), dogs with CVL and L. infantum amastigotes in the intestine; group 2 (G2, n=9), dogs with CVL but without intestinal amastigotes; and group 3 (G3, n=3), uninfected dogs (control group). Granulocytic cells were counted in the crypt-villus unit (mucosa), submucosa, and muscle layer of the intestinal mucosa. Cell counts were higher in the intestinal wall of dogs from G2 followed by G1 and G3 (p≤0.05). In G1, there was a low inverse correlation between parasite burden of the small intestine and granulocyte counts (r= -0.1, p≤0.01). However, in G2 dogs, mast cell and eosinophil numbers showed positive correlation (r=0.85, p≤0.01). The granulocytic cell hyperplasia observed in the intestine of L. infantum-infected dogs suggests that these cells may be involved in the cell-mediated immune response for parasite elimination.

Resumo A leishmaniose visceral (LV) é uma doença causada pelo protozoário Leishmania infantum e pode causar uma reação inflamatória no trato gastrointestinal, entretanto o papel das células granulocíticas (neutrófilos, eosinófilos e mastócitos) no intestino de cães infectados não é totalmente compreendido. Neste estudo realizamos uma análise quantitativa dessas células na parede intestinal de cães com LV. Vinte cães foram distribuídos em três grupos: grupo 1 (G1, n=8), cães com LV e amastigotas de L. infantum no intestino; grupo 2 (G2, n=9), cães com LV, mas sem amastigotas intestinais; e grupo 3 (G3, n=3), não infectados (grupo controle). Células granulocíticas foram contadas na unidade cripta-vilo (mucosa), submucosa e camada muscular da mucosa intestinal. Observamos hiperplasia dessas células na parede intestinal de cães do G2, seguidas das G1 em relação ao G3 (p≤0,05). No G1, houve uma correlação inversa baixa entre a carga parasitária do intestino delgado e a contagem de granulócitos (r= -0,1; p≤0,01). No entanto, nos cães do G2, os números de mastócitos e eosinófilos apresentaram correlação positiva (r=0,85; p≤0,01). A hiperplasia de células granulocíticas observada no intestino de cães infectados por L. infantum sugere que essas células podem estar envolvidas na resposta imune mediada por células para a eliminação do parasita.

Vascular endothelial growth factor, endostatin levels and clinical features among patients with ulcerative colitis and irritable bowel syndrome and among healthy controls: a cross-sectional analytical study

ABSTRACT BACKGROUND: Increased angiogenetic activity in inflammatory bowel disease (IBD) has been shown in previous studies. The aim of this study was to evaluate the relationship of serum vascular endothelial growth factor (VEGF) and endostatin levels with clinical features and mucosal expression in patients with ulcerative colitis (UC). DESIGN AND SETTING: Cross-sectional analytical study conducted in a tertiary-level public hospital. METHODS: Serum VEGF and endostatin levels were determined in 82 individuals: 39 with UC, 28 with irritable bowel syndrome (IBS) and 15 healthy controls (HCs), using enzyme-linked immunosorbent assays (ELISA). VEGF and endostatin expressions were studied using immunohistochemistry (IHC). RESULTS: Mean serum VEGF and endostatin levels were significantly higher in patients with UC than in patients with IBS and in HCs (511.9 ± 377.5 pg/ml, 305.0 ± 121.42 pg/ml and 36.1 ± 40.6 pg/ml; P = 0.001 for VEGF; and 155.50 ± 59.8 ng/ml, 116.9 ± 23.8 ng/ml and 102.2 ± 22.4 ng/ml; P < 0.001 for endostatin, respectively). There was a positive correlation between serum VEGF and endostatin levels (r = 0.422; P < 0.01). Mean H-scores for VEGF expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma, endothelium and epithelium. Mean H-scores for endostatin expression were higher in the active UC group than in the inactive UC and IBS groups, in the stroma and endothelium. There was no endostatin expression in the epithelium. CONCLUSION: Increased endostatin appears to be a defensive reaction to increased VEGF in patients with UC.

Potencial associação da doença celíaca com anemia ferropriva refratária em crianças e adolescentes / Association of potential celiac disease and refractory iron deficiency anemia in children and adolescents

ABSTRACT BACKGROUND: Celiac disease is an enteropathy caused by dietary gluten. The combination of serologic, genetic and histologic data has led to description of other categories of this disease. OBJECTIVE: There are a number of patients with iron deficiency anemia (IDA) that do not respond to iron treatment and may be repeated for many times, Therefore, we aimed to investigate celiac disease in this group. METHODS: In this cross sectional transverse prospective study from August 2011 to February 2013, in a Pediatric care clinic affiliated to Shiraz University of Medical Sciences, 184 children including 92 IDA patients who responded to treatment using iron supplement, 45 non-responding iron deficient patients, and 47 healthy individuals, with the maximum age of 18 years, with written consent from their parents, participated in serologic screening (with Anti-TTG antibody and anti-Endomysial antibody) for celiac disease. Patients with at least one positive serology test underwent multiple mucosal biopsy from bulb and duodenum. RESULTS: Among 184 participants, 19 (10.3%) subjects had positive serologic test for celiac disease, including 13 (28.9%) patients in the group with refractory IDA, 5 (5.4%) patients in the group with treated IDA, and 1 patient in the healthy group. The frequency of positive serologic test in the group with IDA resistant to treatment was prominently higher than the other two groups (P<0.001). Among the patients with positive serologic celiac test who underwent endoscopy and biopsy, no histologic evidence of celiac disease was seen. They were diagnosed as potential celiac disease. CONCLUSION: Frequency of potential celiac disease in patients with refractory IDA was higher than control the subjects. Therefore, we recommend serologic screening for early detection and minimizing the complications of celiac disease and repeated iron therapy for this group.

RESUMO CONTEXTO: A doença celíaca é uma enteropatia causada pelo glúten na dieta. A combinação de dados sorológicos, genéticos e histológicos proporcionou a descrição de outras categorias desta doença. OBJETIVO: Há pacientes com anemia por deficiência de ferro que não respondem ao tratamento com ferro mesmo que repetido por muitas vezes. O objetivo deste trabalho foi investigar a presença de doença celíaca nestes indivíduos. MÉTODOS: Realizado estudo prospectivo com cruzamento secional transversal, de agosto de 2011 a fevereiro de 2013, em uma clínica de cuidados pediátricos afiliados a Shiraz University Medical Sciences, com 184 crianças incluindo 92 pacientes com anemia por deficiência de ferro que responderam ao tratamento com ferro suplementar, 45 não respondedores e 47 indivíduos sadios, com idade máxima de 18 anos, todos com consentimento informado dos pais. Todos participaram da triagem sorológica (com anticorpos anti-TTG e anticorpo antiendomísio) para doença celíaca. Pacientes com pelo menos um teste de sorologia positiva foram submetidos a biópsia da mucosa múltipla do bulbo e duodeno. RESULTADOS: Entre os 184 participantes, 19 (10,3%) tinham teste sorológico positivo para doença celíaca, incluindo 13 (28,9%) pacientes no grupo com a anemia por deficiência de ferro refratária, 5 (5,4%) pacientes no grupo com anemia por deficiência de ferro tratados e respondedores e 1 paciente do grupo saudável. A frequência de teste sorológico positivo no grupo com anemia por deficiência de ferro resistente ao tratamento foi destacadamente maior do que os outros dois grupos (P<0,001). Entre os pacientes com teste sorológico positivo para doença celíaca submetidos a endoscopia e biópsia, não foi vista nenhuma evidência histológica de doença celíaca. Foram diagnosticados como potencial doença celíaca. CONCLUSÃO: Potencial frequência de doença celíaca em pacientes com anemia por deficiência de ferro refratária foi maior do que nos controles. Portanto, recomendamos testes sorológicos de triagem para a detecção precoce, minimizando as complicações da terapia de ferro repetidas para este grupo.

Efeitos da sinvastatina na mucosite gastrointestinal induzida por 5-fluorouracil em ratos / Effects of simvastatin on 5-fluorouracil-induced gastrointestinal mucositis in rats

RESUMO Objetivo: examinar os efeitos da sinvastatina na mucosite gástrica e intestinal após o tratamento com 5-fluorouracil (5-FU), determinados pela expressão de citocinas e histologia em ratos. Métodos: ratos pesando 270±15g foram divididos em dois grupos. O grupo 5-FU+salina foi tratado com 5-FU (50mg/kg) mais solução salina a 0,9% por gavagem uma vez ao dia por cinco dias. O grupo 5-FU+sinvastatina foi tratado com 5-FU (50mg/kg), mais sinvastatina (10mg/kg), da mesma forma. Foi feita a eutanásia dos animais no sexto dia. O estômago e o intestino foram fotografados e removidos para exame. Dosagens séricas de TNF-a, IL-1ß, IL-6 e histopatologia (coloração HE) do estômago e intestino foram realizadas. Resultados: o peso corporal diminuiu em ratos no grupo 5-FU+salina. A sinvastatina não inibiu a perda de peso induzida pelo 5-FU. Danos significativos da mucosa no estômago e no jejuno foram observados em ratos que receberam apenas 5-FU. As dosagens séricas de citocinas foram significativamente menores no grupo 5-FU+sinvastatina do que no grupo 5-FU (p<0,05). A sinvastatina causou efeitos protetores significativos contra as lesões da mucosa gástrica e jejunal induzidas por 5-FU. Conclusão: a sinvastatina atenua a mucosite gástrica e intestinal relacionada à terapêutica com 5-FU. Nossos dados encorajam futuros estudos pré-clínicos e clínicos sobre a utilidade das estatinas na prevenção da mucosite gastrointestinal.

ABSTRACT Objective: simvastatin has pleiotropic anti-inflammatory and immunomodulatory effects potentially usefull to prevent chemotherapy-induced gastrointestinal mucositis. Studies on this are scarce. This study aimed to examine the effects of simvastatin on gastric and intestinal mucositis after 5-fluorouracil (5-FU) treatment in rats. Methods: rats weighing 270±18g were divided into two groups. The 5-FU+saline group (5-FU/SAL) rats were treated with 5-FU (50mg/kg) plus 0.9% saline orally (gavage) once daily for five days. The 5-FU+simvastatin (5-FU/SIMV) group was treated with 5-FU (50mg/kg), plus simvastatin (10mg/kg), in the same way. The rats were euthanased on the sixth day, then their stomach and intestine were photographed and removed for exams. Dosages of serum TNF-a, IL-1ß, IL-6 and histopathology were done for stomach and intestine. Results: body-weight was significantly lower in rats treated with 5-FU+saline than the weight loss of the 5-FU/SIMV group rats. TNF-a expression was lower in 5-FU/SIMV group (172.6±18pg/ml) than in 5-FU/SAL (347.5±63pg/ml). Serum IL-1b was lower in 5-FU/SAL group (134.5±23pg/ml) than in 5-FU/SIMV (48.3±9pg/ml). Serum IL-6 was 61.8±15pg/ml in 5-FU/SIMV and 129.4±17pg/ml in 5-FU/SAL groups. These differences were significant (p<0.05). Mucosal damage in stomach and jejunum were observed in rats receiving 5-FU alone. In the stomach and jejunum, simvastatin caused significant protective effects against 5-FU-induced mucosal injury. Conclusion: simvastatin attenuated gastric and intestinal mucositis related to 5-FU therapeutics in animal model. These data encourage forthcoming clinical studies addressing the usefulness of statins in the prevention and treatment of gastrointestinal mucositis.

Are there differences in the growth adaptation processes of growing and mature organism models of short bowel syndrome?

OBJECTIVES: The purpose of this study was to present an experimental model of short bowel syndrome (SBS) in weaning rats and to compare the adaptative mechanisms of the remaining bowel in weaning rats and adult animals by means of morphometric, histologic and molecular methods. METHODS: Twenty-four weaning rats were divided into 3 groups of 8 animals, one control group and two short bowel groups (euthanasia after 4 and 21 days), and were compared with similar adult groups. Morphometric evaluations of the animals and histopathological and molecular studies of the remaining bowel were performed. RESULTS: The weight of young rats increased after enterectomy, whereas that of adult rats decreased after enterectomy (p<0.0001). The ratio of intestinal length/body weight was significantly higher in weaning rats than in adults (p<0.002), showing that intestinal growth was more intense in weaning rats. Intestinal resection promoted increased thickness of the small bowel lamina propria (p=0.001) and reduced thickness of the colon lamina propria (p=0.04) in weaning rats relative to those in adults. In addition, intestinal resection promoted increased expression of the Bcl-xl gene (antiapoptotic) in adult animals compared with that in weaning rats (p=0.001). CONCLUSION: Morphometric, histological and molecular differences were shown in the adaptation processes of growing and mature organisms.

Anemia crónica grave por Ancylostoma duodenale en Ecuador: diagnóstico por duodenoscopia / Chronic and severe anemia caused by Ancylostoma duodenale in Ecuador: diagnosis by duodenoscopy

Resumen Durante 11 años un varón de 38 años de edad, residente en una región subtropical de Ecuador, había sido diagnosticado de anemia crónica y tratado con transfusiones de sangre en un hospital de la provincia de Cotopaxi, Ecuador. Fue transferido a Quito por una anemia grave, con hemoglobina de 4 g/dL. Se realizó una duodenoscopia en que se observaron nemátodos adultos, identificados posteriormente como Ancylostoma duodenale. El paciente fue tratado exitosamente con albendazol durante cinco días consecutivos y transfusiones de sangre. En el seguimiento a los ocho meses, no se encontró anemia ni huevos de anquilostomas en el examen de heces.

For 11 years, a 38-year-old male residing in a subtropical region of Ecuador, was repeatedly diagnosed with chronic anemia, and treated with blood transfusions in a hospital of province of Cotopaxi, Ecuador. He was transferred to Quito for severe anemia, having hemoglobin of 4 g/dL. Duodenoscopy was performed and adult nematodes, identified later as Ancylostoma duodenale, were observed. The patient was successfully treated with albendazole for five consecutive days and given blood transfusions. In the control visit at eight months, without anemia and no hookworm ova in the stool examined were found.

Transitional metaplasia in intestinal epithelium of rats submitted to intestinal cystoplasty and treatment with L -lysine

Abstract Purpose: To evaluated the effects of L-lysine on the intestinal and urothelial epithelia in cystoplasty in rats. Methods: Twenty-eight 9-week-old rats were assigned to 4 groups: Group A (n=8) cystoplasty followed by administration of L-lysine (150 mg/kg body weight by gavage) for 30 weeks; Group B (n=8) cystoplasty + water for 30 weeks; Group C (n=6) L-lysine for 30 weeks; Group D (n=6) water for 30 weeks. Results: On histopathology with hematoxylin and eosin, mild to moderate hyperplasia transitional was observed in at the site of anastomosis in all animals submitted to cystoplasty (Groups A and B), but "transitional metaplasia" of the intestinal glandular epithelium was more accentuated in Group A (p=0.045). No inflammatory cells, dysplasia or abnormalities were observed. Staining with Alcian blue revealed a substantial reduction of goblet cells and mucins in the colon segment (Groups A and B). Conclusion: The administration of L-lysine to rats accelerated the development of transitional metaplasia in the epithelium of the colon segment in cystoplasty.

Tissue sulfomucin and sialomucin content in colon mucosa without intestinal transit subjected to intervention with Curcuma longa (curcumin)

Abstract Purpose: To measure the tissue sulfomucin and sialomucin content of the colon mucosa without fecal flow, subjected to intervention with curcumin, and the influence of the concentration used and the intervention time. Methods: Thirty-six rats were subjected to proximal right colostomy and distal mucous fistula. They were divided into two groups according to whether sacrifice was performed two or four weeks after the intervention. Each group was divided into three subgroups according to the enema applied daily: saline alone; curcumin at 50 mg/kg/day or curcumin at 200 mg/kg/day. Acid mucins were diagnosed using the Alcian blue technique. The mucin content was quantified by means of computer-assisted image analysis. The significance level of 5% was used throughout (p < 0.05). Results: There were dose-related increases in the quantities of sulfomucins in the animals subjected to interventions with curcumin, both after two weeks (p < 0.00001) and after four weeks (p < 0.00001). There were increases in sialomucin quantity that were concentration-related (p < 0.00001) and time-related (p < 0.00001). Conclusion: Curcumin enemas increase the quantity of acid mucins in the intestinal flow in the excluded colon, with dose and time dependency.

[Retracted Article] Gastric and jejunal histopathological changes in patients undergoing bariatric surgery / [Artigo Retratado] Alterações histopatológicas gástricas e jejunais em pacientes submetidos à cirurgia bariátrica

ABSTRACT BACKGROUND Morbid obesity is a multifactorial disease that is increasingly treated by surgery. OBJECTIVE To evaluate gastric histopathological changes in obese, and to compare with patients who underwent gastrojejunal bypass and the jejunal mucosa after the surgery. METHODS This is an observational study performed at a tertiary public hospital, evaluating endoscopic biopsies from 36 preoperative patients and 35 postoperative. RESULTS In the preoperative group, 80.6% had chronic gastritis, which was active in 38.9% (77.1% and 20.1%, respectively, in the postoperative). The postoperative group had a significant reduction in Helicobacter pylori infection (P=0.0001). A longer length of the gastric stump and a time since surgery of more than two years were associated with Helicobacter pylori infection. The jejunal mucosa was normal in 91.4% and showed slight nonspecific chronic inflammation in 8.6%. CONCLUSION There was a reduction in the incidence of Helicobacter pylori infection in the postoperative group. A longer length of the gastric stump and longer time elapsed since surgery were associated with Helicobacter pylori infection. The jejunal mucosa was considered normal in an absolute majority of patients.

RESUMO CONTEXTO A obesidade mórbida é doença multifatorial cujo tratamento cirúrgico é cada vez mais indicado. OBJETIVO Avaliar alterações histopatológicas gástricas em obesos e comparar com os submetidos à bypass gastrojejunal e a mucosa jejunal após a operação. MÉTODOS Estudo observacional realizado em hospital público terciário avaliando biópsias endoscópicas de 36 pacientes no pré-operatório e 35 no pós-operatório. RESULTADOS: No pré-operatório 80,6% apresentaram gastrite crônica, 38,9% em atividade (77,1% e 20,1%, respectivamente, no pós-operatório). O grupo pós-operatório apresentou diminuição significativa na infecção por Helicobacter pylory (P=0,0001). Maior comprimento do coto gástrico e tempo de operação superior a dois anos associaram-se a infecção por Helicobacter pylori. A mucosa jejunal foi normal em 91,4% e apresentava leve inflamação crônica inespecífica em 8,6%. CONCLUSÃO Houve diminuição da infecção por Helicobacter pylori após a operação. Maior comprimento do coto gástrico e do tempo de operação associaram-se à infecção por Helicobacter pylori. A mucosa jejunal foi considerada normal na maioria absoluta dos pacientes do grupo pós-operatório.

Claudin-3 and occludin content in the glands of colonic mucosa devoid from fecal stream submitted to topical intervention with oil extract of Curcuma longa

Abstract Purpose: To evaluate the inflammatory intensity and measure the tissue content of the proteins claudin-3 and occludin in the colonic mucosa without fecal stream submit to intervention with curcumin. Methods: Thirty-six rats were submitted to a proximal colostomy and a distal mucous fistula and divided into two groups according to sacrifice to be performed two or four weeks. Each group was divided into three subgroups according daily application of enemas containing saline, curcumin at 50 mg/kg/day or 200 mg/kg/day. Colitis was diagnosed by histological analysis. Claudin-3 and occludin were determined by immunohistochemistry. The tissue content of claudin-3 and occludin were quantified by computer-assisted image analysis. Mann-Whitney, Student t and ANOVA tests were used to analyze the results establishing the level of significance of 5% for both (p<0.05). Results: Curcumin at both concentrations reduces the inflammation and preserves the tissue content of the proteins claudin-3 and occludin, which was related to the concentration used and to the time of the intervention. Conclusion: The application of enemas with curcumin reduces inflammation and preserves the tissue content of the proteins claudin-3 and occludin in the colonic mucosa devoid from the fecal stream.

Effects of heme oxygenase-1 recombinant Lactococcus lactis on the intestinal barrier of hemorrhagic shock rats

This study aimed to investigate the effects of heme oxygenase-1 recombinant Lactococcus lactis (LL-HO-1) on the intestinal barrier of rats with hemorrhagic shock. One hundred Sprague-Dawley male rats (280–320 g) were randomly divided into healthy control group (N group) and hemorrhagic shock group (H group). Each group was subdivided into HO1t, HO2t, HO3t, PBS and LL groups in which rats were intragastrically injected with LL-HO-1 once, twice and three times, PBS and L. lactis (LL), respectively. The mortality, intestinal myeloperoxidase (MPO) activity, intestinal contents of TNF-α, IL-10 and HO-1, and intestinal Chiu's score were determined. Results showed that in N group, the HO-1 content increased after LL-HO-1 treatment, and significant difference was observed in HO1t group and HO2t group (P<0.05). In H groups, MPO activity and Chiu's score decreased, but IL-10 content increased in LL-HO-1-treated groups when compared with PBS and LL groups (P<0.05). When compared with N group, the MPO activity reduced dramatically in LL-HO-1-treated groups. Thus, in healthy rats (N group), intragastrical LL-HO-1 treatment may increase the intestinal HO-1 expression, but has no influence on the intestinal barrier. In hemorrhagic shock rats, LL-HO-1 may significantly protect the intestinal barrier, and repeating the intragastrical LL-HO-1 treatments twice has the most obvious protection.

Probiotic therapy reduces inflammation and improves intestinal morphology in rats with induced oral mucositis

Abstract The aim of the present study was to evaluate the effect of systemic administration of probiotics (PROB) on the progression of experimentally induced oral and intestinal mucositis in rats immunosuppressed by chemotherapy (5-fluorouracil: 5-FU). Twenty-four rats were divided into the following groups (n=6): GC (control), GPROB, G5FU and G5-FU/PROB. Groups GPROB and G5-FU/PROB received 1 g of probiotic incorporated into each 100 g of feed (Bacillus subtilis, Bifidobacterium bifidum, Enterococcus faecium and Lactobacilllus acidophilus), beginning 30 days before oral mucositis induction. Groups G5FU and G5-FU/PROB received 60 mg/kg of 5-FU on days 0 and 2. The left oral mucosa of each animal was irritated by mechanical trauma (days 1 and 2). On days 3 and 7, three animals from each group were sacrificed, and their oral mucosa and small intestine were biopsied and processed for histopathological analysis. Groups G5-FU and G5-FU/PROB showed ulcerated oral lesions at day 3, with progression in group G5-FU and regression in group G5-FU/PROB at day 7. Histologically, less severe signs of inflammation in the oral mucosa were observed in group G5-FU/PROB than in group G5-FU. Regarding the intestine, villus-related defects of lesser magnitude were observed in group G5-FU/PROB, compared with group G5-FU. Group GPROB showed greater villus height than group GC. It can be concluded that probiotic supplementation reduced oral and intestinal inflammation in immunosuppressed rats with experimentally induced mucositis, and may protect the intestine from changes induced by chemotherapy, thus contributing to overall health.