Campsiandra laurifolia reduces oxidative stress and Iiflammation in rats with ulcerative colitis

Ulcerative colitis (UC) affects the mucosa and submucosa of the large intestine. One of the mechanisms involved in its etiology is oxidative stress (OS), directly involved in the inflammatory process characteristic of UC. The Campsiandra laurifolia, known as acapurana, was described as possessing antioxidant properties. We used 24 male Wistar rats, divided into control (CO), control + acapurana (CO + A), colitis (CL), and colitis + acapurana (CL + A) groups. This study performed histological analysis, measuring anal sphincter pressure (ASP) and lipoperoxidation (LPO). The activity of the antioxidant enzyme superoxide dismutase (SOD) and glutathione (GSH) levels were evaluated. The expression of the nuclear factor kappa B (NFkB) and inducible nitric oxide synthase (iNOS) was analyzed by immunohistochemistry. The statistical analysis used was the one-way analysis of variance (ANOVA), followed by the Student-Newman-Keuls test; values were expressed as mean ± standard error, and the significance level was p < 0.05. In the animals of the CL group, we observed the destruction of the crypts and the presence of mucosal ulcers, edema, and submucosal inflammatory infiltrate, as well as increased damage to the intestinal mucosa, reduced ASP, increased LPO and SOD activity, reduced GSH levels, and increased expression of NFkB and iNOS. The administration of C. laurifolia in the CL + A group was shown to cause regeneration of crypts, reduction of inflammatory infiltrate, reduction of damage to the intestinal mucosa, increase in ASP, and reduction in LPO with the restoration of SOD activity and GSH levels. The immunohistochemistry of NFkB and iNOS was significantly reduced. Therefore, the C. laurifolia aqueous extract appears to exert an antioxidant and anti-inflammatory effect in rats with AA-induced colitis. (AU)

DIAGNOSIS AND MANAGEMENT OF CHRONIC IDIOPATHIC CONSTIPATION: A NARRATIVE REVIEW FROM A BRAZILIAN EXPERT TASK FORCE.

BACKGROUND: Chronic idiopathic constipation (CIC) is a condition that widely affects the global population, represents relevant healthcare resource utilization and costs, and impacts the individual's well-being. OBJECTIVE: To review the consensus of expert societies and published guidelines on the diagnosis and treatment of CIC in adults, seeking to assist reasoning and decision-making for medical management of patients with CIC and provide a practical reference material. METHODS: A Brazilian medical task force searched the scientific literature in the following electronic databases: MEDLINE/PubMed, SciELO, EMBASE and Cochrane, using the following descriptors: chronic constipation, diagnosis, management of chronic constipation. In addition, a review of articles on the mechanism of action, safety, and efficacy of therapeutic options available in Brazil was carried out. RESULTS: The diagnostic approach and the understanding of the pathophysiology present in CIC are essential items to indicate the appropriate therapy and to understand the ecosystem of the patient's needs. CONCLUSION: CIC is a common condition in adults, occurring more frequently in the elderly and in women. Proper management is defined by detailed medical history and physical examination, together with appropriate therapeutics, regardless pharmacological or not, and depending on the best moment of indication. This way, the impact on quality of life is also optimized.

Diagnóstico e abordagem terapêutica da constipação idiopática crônica: uma revisão de especialistas brasileiros / Diagnosis and management of chronic idiopathic constipation: a narrative review from a brazilian expert task force

ABSTRACT Background Chronic idiopathic constipation (CIC) is a condition that widely affects the global population, represents relevant healthcare resource utilization and costs, and impacts the individual's well-being. Objective To review the consensus of expert societies and published guidelines on the diagnosis and treatment of CIC in adults, seeking to assist reasoning and decision-making for medical management of patients with CIC and provide a practical reference material. Methods A Brazilian medical task force searched the scientific literature in the following electronic databases: MEDLINE/PubMed, SciELO, EMBASE and Cochrane, using the following descriptors: chronic constipation, diagnosis, management of chronic constipation. In addition, a review of articles on the mechanism of action, safety, and efficacy of therapeutic options available in Brazil was carried out. Results The diagnostic approach and the understanding of the pathophysiology present in CIC are essential items to indicate the appropriate therapy and to understand the ecosystem of the patient's needs. Conclusion CIC is a common condition in adults, occurring more frequently in the elderly and in women. Proper management is defined by detailed medical history and physical examination, together with appropriate therapeutics, regardless pharmacological or not, and depending on the best moment of indication. This way, the impact on quality of life is also optimized.

RESUMO Contexto A constipação idiopática crônica (CIC) é uma condição que afeta amplamente a população global, representa um grande custo econômico, causa substancial utilização de recursos em saúde e impacta o bem-estar do indivíduo. Objetivo Revisar os consensos de Sociedades de especialistas e diretrizes publicados sobre o diagnóstico e tratamento da CIC em adultos, buscando auxiliar o raciocínio e a tomada de decisão para a conduta médica frente ao paciente e oferecer um material prático de referência. Métodos Uma força tarefa médica brasileira realizou uma busca na literatura científica nas bases de dados eletrônicos Medline/PubMed, SciELO, Embase e Cochrane, tendo sido utilizados os seguintes descritores: chronic constipation, diagnosis, management of chronic constipation. Adicionalmente, foi realizada uma revisão de artigos sobre o mecanismo de ação, segurança e eficácia das opções terapêuticas disponíveis no Brasil. Resultados A abordagem diagnóstica e o entendimento da fisiopatologia presente na CIC são itens fundamentais para que seja indicada a terapêutica apropriada e seja compreendido o ecossistema de necessidades do paciente. Conclusão A CIC é uma condição comum em adultos, ocorrendo com maior frequência em idosos e mulheres. O manejo correto é definido pela anamnese e exame físico detalhados, juntamente com a terapêutica apropriada, independentemente de ser farmacológica ou não, conforme o melhor momento de indicação. Desta forma, o impacto na qualidade de vida também é otimizado.

Tissue factor expression in colorectal adenocarcinoma: association with angiogenesis and clinical and pathological aspects

Introduction: Tissue factor (TF) expression has been described in various neoplasms and was correlated with angiogenesis and metastases. Objectives: To describe TF expression in colorectal cancers, correlating it with microvessel density and clinical and pathological variables. Methods: Immunohistochemistry was used to determine TF expression and microvessel density. The Student t-test was used to compare high and low TF expression with microvessel density andwith age. The chi-squared test was used for other comparisons, and Kaplan-Meier curves were used for survival analyses. Results: Forty-three patients were operated with curative intent. Their mean age was 58.1±12.6 years old, and 62.8% were male. The rectum was the most common location (60,4%), and most tumors reached the serosa and peri-intestinal fat (72.1%). Lymph nodes were positive in 46.5%, and 72.1% of the tumors were moderately differentiated adenocarcinomas. Death occurred in 27.6±12.8months in 51.1% of the patients who had recurrence. Tissue factor expression was intense in 88.4%. There was a positive correlation between TF expression and microvessel density (p=0.02), and between TF and older age (p< 0.01). There was no correlation between TF expression and other variables (gender, histological type, penetration into the intestinal wall, and lymphatic and systemic metastases). Tissue factor expression did not correlate with survival. Conclusion: Tissue factor expression correlated with increased microvessel density and older age. Further studies are necessary to ascertain the clinical relevance of TF in colorectal cancer. (AU)

Ovarian metastasis from colorectal adenocarcinoma / Metástase ovariana de adenocarcinoma colorretal

Introduction: Ovarian metastases of gastrointestinal origin, also called Krukenberg tumors, have a guarded prognosis. Physicians need to look for alternatives in diagnosis and treatment for this clinical condition in order to improve the outcome of the patients. Objectives: To report the experience of the authors in the treatment of these patients, and to perform a review of the literature on the epidemiology, clinical presentation, diagnosis, treatment, and prognosis for ovarian metastases from colorectal cancer. Methods: We collected clinical information regarding the patients treated for ovarian metastasis from colorectal adenocarcinoma at our coloproctology service, and performed a search on the PubMed database using the terms colorectal cancer, ovarian metastasis, Krukenberg tumor and surgery. Conclusion: Large abdominal tumors are the most frequent presentation of ovarian metastasis from colorectal cancer. The diagnosis is based on a histopathological analysis, levels of carcinoembryonic antigen (CEA) and cancer antigen 125 (CA-125), and immunohistochemical studies for the cytokeratin 20 (CK20), caudal-type homeobox 2 (CDX2) and vilina markers. Citoreductive surgical procedures are the most promising approach to treatment, with the highest impact on overall survival. The prognosis is negatively influenced by the extent of the metastasis, by citoreductive surgical procedures with persistence of macro- or microscopic foci of the disease, and by low scores on the general well-being index of the patient. (AU)

Introdução: As metástases ovarianas de tumores gastrointestinais, também chamadas de tumores de Krukenberg, são neoplasias de prognóstico reservado. Exigem conhecimento de alternativas diagnósticas e terapêuticas para garantir melhora da sobrevida das pacientes. Objetivos: Relatar a experiência dos autores no tratamento dessas pacientes, e fazer uma revisão da literatura sobre a epidemiologia, apresentação clínica, diagnóstico, tratamento e prognóstico das metástases ovarianas do câncer colorretal. Métodos: Foi realizada uma coleta de informações clínicas de pacientes tratados por metástases ovarianas de adenocarcinoma colorretal em nosso serviço de coloproctologia, em conjunto com uma pesquisa na base de dados PubMed com os termos colorectal cancer, ovarian metastasis, Krukenberg tumor, e surgery. Conclusão: Volumosas massas abdominais constituem a principal apresentação clínica da doença. As alternativas diagnósticas incluem a avaliação histopatológica, a identificação dos níveis de antígeno cárcino-embriônico (ACE) e de antígeno de câncer 125 (CA-125), e exame imunoistoquímico de espécimes cirúrgicos para os marcadores citoqueratina 20 (CK20), homeobox 2 do tipo caudal (CDX2), e vilina. O tratamento citorredutor completo demonstrou o maior impacto na sobrevida dos pacientes. O prognóstico é influenciado negativamente pela extensão da doença metastática, por cirurgia citorredutiva com persistência focos microscópicos ou macroscópicos da doença, e baixo escore de índice de bem-estar geral do paciente. (AU)

Antioxidant evaluation of the aqueous extract of hulls of Campsiandra laurifolia in colitis induced by acetic acid in Wistar rats / Avaliação antioxidante do extrato aquoso de cascas de Campsiandra laurifolia na colite induzida por ácido acético em ratos Wistar

Abstract Due to the ethnopharmacological use of Campsiandra laurifolia (Fabaceae), popularly known as Acapurana, to treat wounds and ulcers, associated with the lack of alternative treatments for intestinal inflammations such as ulcerative colitis (UC), the present work sought to characterize its phytochemical and antioxidant activities, and to evaluate remedial action in experimental colitis with acetic acid. Phytochemical analyzes were performed through qualitative and quantitative colorimetric tests of the main secondary metabolites. In the colitismodel, 24male Wistar rats aged±60 days oldwere used, divided into 4 groups: Control (CO) control+aqueous extract of C. laurifolia 50mg/kg (CO+A50); Colitis (CL); and Colitis+aqueous extract of C. laurifolia 50 mg/kg (CL+ A50).Measurement of sphincter anal pressure and histological tests of the large intestine, lipoperoxidation (LPO), enzymeactivity of superoxide dismutase (SOD), and levels of glutathione (GSH)were performed. For statistical analysis, the oxidative stress (OS) results were expressed as means±standard error, adopting a significance level of p < 0.05. The screening indicated the presence of flavonoids, saponins and tannins in the extract, with high levels of phenolic

Resumo Devido ao uso etnofarmacológico de Campsiandra laurifolia (Fabaceae), popularmente conhecida comoAcapurana, para tratar feridas e úlceras, associado à falta dealternativas de tratamentos para as inflamações intestinais como a retocolite ulcerativa (RCU), o presente trabalho buscou caracterizar sua constituição fitoquímica, sua atividade antioxidante, e avaliar sua ação reparadora na colite experimental com ácido acético. As análises fitoquímicas foram realizadas por meio de ensaios colorimétricos qualitativos e quantitativos dos principaismetabólitos secundários.Nomodelo de colite, foramutilizados 24 ratos machos Wistar de±60 dias de idade, divididos em 4 grupos: Controle (CO), controle+ extrato aquoso de C. laurifolia 50mg/kg (CO+A50); Colite (CL); e Colite+extrato aquoso de C. laurifolia (CL+ A50). Foram realizadas aferições da pressão anal esfincteriana e avaliações histológicas do intestino grosso, lipoperoxidação (LPO), atividade da enzima superóxido dismutase (SOD) e níveis da glutationa (GSH). Para a análise estatística, resultados do estresse oxidativo (EO) foram expressos em médias±erro padrão, adotando um nível de significância de p < 0,05. O screening indicou no extrato a presença de flavonoides, saponinas e taninos com altos teores de compostos fenólicos e taninos, relacionando-os a uma elevada capacidade antioxidante. Na análise histológica, o grupo CL apresentou perda das criptas, do edema e do infiltrado inflamatório. O uso do extrato de C. laurifolia reestruturou as criptas, diminuiu o edema e aumentou a pressão anal esfincteriana, com diminuição da LPO, da SOD, e aumento da GSH. Sugere-se que o uso do extrato de C. laurifolia diminui o EO por seu poder antioxidante, conferido pelos compostos fenólicos presentes no extrato.

General recommendations to the colorectal surgeon during the COVID-19 pandemic / Recomendações gerais ao coloproctologista durante a pandemia do COVID-19

Abstract The COVID-19 pandemic has shown our country in an unfavorable light, as Brazil has reported the second highest number of deaths to date. When the social isolation phase is finished, professional activities (including the medical ones) will resume their routines and the specialist must be updated in order to provide effective and safe care. Although many published recommendations are based on low levels of evidence, disclosing them has become necessary, since the coronavirus infection may affect operative outcomes. Overall, it is suggested that physicians adopt preventive measures, starting with the medical appointment, and extending them to the surgical procedure. Furthermore, it is also necessary to provisionally change criteria for operative indications and conducts. Currently, postponing elective surgeries seems to be a universally agreed decision. Moreover, we need to establish the early diagnosis of the viral infection, before or after the surgery. Several safety measures related to minimally-invasive procedures have been reported, disclosing the risks of aerosol dissemination by the pneumoperitoneum and smoke from energy-powered devices. The present article aimed to bring to the colorectal surgeon the current recommendations and general safety measures in order to prevent infection dissemination, to improve surgical planning in terms of timing and specific technical aspects.

Resumo A pandemia pelo COVID-19 colocou o Brasil hoje numa situação de destaque negativo, porque somos o segundo país com maior número de casos no mundo. Ao finalizarmos o período de afastamento social, as atividades profissionais, incluindo as médicas, serão restabelecidas, e o especialista necessita estar atualizado a fim de prover o melhor nível de trabalho, de maneira segura. Apesar de muitas das recomendações estarem baseadas em opiniões e estudos sem muito grau de evidência, sua divulgação nesse momento torna-se necessária, uma vez que a infecção pelo coronavírus afeta os resultados operatórios. De maneira geral, o médico deve assumir medidas preventivas desde o momento em que agenda uma consulta até a realização do procedimento cirúrgico. Além disso, é necessário considerar a necessidade de mudar provisoriamente os critérios de indicação cirúrgica, e até as condutas operatórias. Parece existir um pensamento uniforme no sentido de adiar cirurgias eletivas. Da mesma forma, devemos reconhecer a infecção viral precocemente, antes ou após a cirurgia. Diversas medidas preventivas relacionadas aos procedimentos minimamente invasivos já foram descritas, realçando o poder de disseminação pelo aerossol gerado nesses procedimentos e no uso de instrumentos de energia. O presente artigo visou apresentar ao coloproctologista as recomendações atuais e cuidados gerais para prevenir disseminação da infecção, e como planejar o tratamento cirúrgico com mais segurança em termos de momento da cirurgia e aspectos técnicos específicos.

Potential impact of COVID-19 on colorectal disease management / Impacto potencial da COVID-19 no manuseio das doenças colorretais

Abstract The current recommendations for management of colorectal diseases are still evolving, due to the limited experience on this issue. As the new coronavirus can be transmitted through breath droplets, by contact and orofecally, there is no consensus of how this fact may affect the investigation and treatment of anorectal diseases. Thus, high-quality multicenter studies are urgently needed to provide better information to both patients and the multiprofessional team, in order to build an effective pandemic response plan in our specialty. As a greater operative risk for infected patients has already been demonstrated, the next step lies on the identification of new therapeutic strategies that could minimize this effect on an individual basis. There is a present understanding that the COVID-19 pandemic should change some traditional practices. Therefore, the surgical treatment of suspected or known COVID-19 case demands specific insights. This article analyses potential influences regarding the treatment of patients with Colorectal Cancer (CRC) and Inflammatory Bowel Diseases (IBD). At present, elective surgery must be avoided, and the colorectal surgeon must carefully evaluate the risks and benefits of such decision. Within this context, a change toward nonsurgical and less aggressive modalities of CRC treatment may help to postpone definitive treatment. We also discuss the concerns regarding the viral infection among the population, the influence on clinical symptoms and the proposed modifications on therapeutic schemes.

Resumo As recomendações atuais para manuseio das doenças colorretais ainda estão em evolução, devido à limitada experiência nesse tema. Como o novo coronavírus pode ser transmitido em gotículas da respiração, por contato ou por via oro-fecal, ainda não existe consenso de como este fato pode afetar a investigação e o tratamento de doenças anorretais. Assim, são necessários estudos multicêntricos de qualidade para prover melhor informação ao paciente e equipe multiprofissional, possibilitando a formulação de uma resposta efetiva à pandemia em nossa especialidade. Uma vez que o risco operatório de pacientes infectados é maior, o passo subsequente reside em identificar novas estratégias terapêuticas que possam minimizar esse efeito individualmente. Assim, reconhece-se atualmente que a pandemia pelo COVID-19 deve alterar algumas práticas tradicionais. Consequentemente, o tratamento cirúrgico de um doente infectado ou suspeito demanda reflexões específicas. Esse artigo analisa influências potenciais relacionadas ao tratamento do Câncer Colorretal (CCR) e Doenças Inflamatórias Intestinais (DII). No atual momento, cirurgias eletivas devem ser postergadas e o cirurgião colorretal deve avaliar cuidadosamente os riscos e benefícios dessa decisão. Nesse contexto, uma mudança na direção de modalidades não-cirúrgicas e menos agressivas do CCR pode favorecer a prorrogação do tratamento definitivo. Aqui também se discutem as preocupações sobre a infecção viral em pacientes com DII, sua influência sobre os sintomas clínicos e as modificações propostas nos esquemas terapêuticos.

ARE OBESITY AND ADENOMA DEVELOPMENT ASSOCIATED AS COLORECTAL CANCER PRECURSORS?

BACKGROUND: One of the most important concerns on health is the increased rates of obesity in population and the speed in which this number is increasing. This number translates a serious public health problem, since it also increases the risk of several other diseases associated with obesity resulting in significant morbidity and mortality. Among them, it seems to be connected to several neoplasms, such as colorectal carcinoma. AIM: To evaluate the impact of obesity as a risk factor for colorectal carcinoma through the detection of adenoma, and to discuss the mechanisms that could establish a link between obesity and neoplasm. METHODS: Patients who underwent colonoscopy were included. Personal and anthropometric data, clinical history, and results of the tests were analyzed in order to verify the correlation of BMI and the presence of adenomatous polyps. RESULTS: A total of 142 patients were studied, which a mean age of 62 years. Of the patients, 74 (52.1%) were men and 68 (47.9%) were. Obesity was identified in 16.2% of the patients. Polyps were found in 61 (42.9%), mostly smaller than 1 cm. Obese individuals were 1.56 times more likely to present colorectal adenoma than patients with normal weight. CONCLUSION: This study, although showing the greater presence of colorectal adenomas in obese individuals, did not show a significant difference in the occurrence of pre-malignant lesions.

Anal mycobacterial infections / Infecções micobacterianas do ânus

Abstract Background Mycobacterial infections are a serious public health problem worldwide. Involvement of the anal canal and perineum is very rare, but constitute an important differential diagnosis with other equally serious pathologies that may affect the region, such as malignant neoplasms and Crohn's disease. Objectives To conduct a literature review on mycobacterial infections of the perianal region considering the most recent information for diagnostic and therapeutic guidance of this disease. Methods Research was performed on the PUBMED and LILACS databases with the expressions Mycobacterium, Anal, Infection and Tuberculosis. We reviewed articles referring to series of treated cases, clinical reports and literature review published since 2005. Results Information was compiled on the epidemiology of mycobacterial infections; the clinical behavior of affected individuals; diagnostic options and their validity in clinical practice; and, finally, therapeutic options. Conclusions Mycobacterial infections of the anus and perineum are rare. The most common clinical presentations are the presence of ulceration and fistulization. The diagnosis involves more than one procedure for identifying the bacilli and should consider the presence of manifestations in more than one organ. The treatment is based on pharmacological intervention. Surgery is recommended for acute complications or chronic sequelae of the disease.

Resumo Introdução Infecções micobacterianas constituem um grave problema de saúde pública a nível mundial. As manifestações anoperineais são raras, mas constituem um importante diagnóstico diferencial com outras patologias igualmente graves que podem acometer a região, como as neoplasias malignas e a doença de Crohn. Objetivos Realizar um levantamento da literatura sobre infecções micobacterianas da região anoperineal, considerando as informações mais atuais para orientação diagnóstica e terapêutica dessa enfermidade. Métodos Foi realizada pesquisa nos bancos de dados PUBMED e LILACS com as expressões Mycobacterium, Anal, Infection e Tuberculosis. Foram revisados artigos referentes a séries de casos tratados, relatos clínicos e revisão da literatura publicada a partir de 2005. Resultados Foram compiladas informações sobre a epidemiologia das infecções micobacterianas; o comportamento clínico dos indivíduos afetados; opções diagnósticas e sua validade na prática clínica; e, por fim, opções terapêuticas. Conclusões Infecções micobacterianas da região anoperineal são raras. As apresentações clínicas mais comuns são a formação de ulceras e a fistulização. O diagnóstico envolve mais de um procedimento para identificação dos bacilos, e deve considerar a presença de manifestações em mais de um órgão. O tratamento é principalmente medicamentoso, sendo a cirurgia recomendada nas complicações agudas ou sequelas crônicas da doença.

Are obesity and adenoma development associated as colorectal cancer precursors? / Obesidade e desenvolvimento de adenoma estão associados como precursores do câncer colorretal?

ABSTRACT Background: One of the most important concerns on health is the increased rates of obesity in population and the speed in which this number is increasing. This number translates a serious public health problem, since it also increases the risk of several other diseases associated with obesity resulting in significant morbidity and mortality. Among them, it seems to be connected to several neoplasms, such as colorectal carcinoma. Aim: To evaluate the impact of obesity as a risk factor for colorectal carcinoma through the detection of adenoma, and to discuss the mechanisms that could establish a link between obesity and neoplasm. Methods: Patients who underwent colonoscopy were included. Personal and anthropometric data, clinical history, and results of the tests were analyzed in order to verify the correlation of BMI and the presence of adenomatous polyps. Results: A total of 142 patients were studied, which a mean age of 62 years. Of the patients, 74 (52.1%) were men and 68 (47.9%) were. Obesity was identified in 16.2% of the patients. Polyps were found in 61 (42.9%), mostly smaller than 1 cm. Obese individuals were 1.56 times more likely to present colorectal adenoma than patients with normal weight. Conclusion: This study, although showing the greater presence of colorectal adenomas in obese individuals, did not show a significant difference in the occurrence of pre-malignant lesions.

RESUMO Racional: Uma das grandes preocupações no âmbito da saúde é o crescente índice de obesidade na população e a velocidade com que esse número vem aumentando. Ele constitui grave problema de saúde pública, uma vez que aumenta também o risco de inúmeras doenças associadas à obesidade e que resultam em morbimortalidade significativa, como o câncer colorretal. Objetivo: Avaliar o impacto da obesidade como fator de risco para câncer colorretal, através da detecção de adenomas colorretais, e discutir os mecanismos que podem estabelecer uma ligação entre esta neoplasia e a obesidade. Métodos: Foram incluídos pacientes submetidos à colonoscopia. Dados pessoais e antropométricos, antecedentes clínicos e laudos dos exames foram analisados, a fim de verificar a correlação do IMC e a presença de pólipos adenomatosos. Resultados: Foram estudados 142 pacientes, 74 (52,1%) homens e 68 (47,9%) mulheres, com média de 62 anos. A obesidade foi identificada em 16,2% dos pacientes. Pólipos foram encontrados em 61 (42,9%), sendo em sua maioria menores do que 1 cm. Obesos tiveram probabilidade 1,56 vez maior de apresentar adenoma colorretal que pacientes com peso normal. Conclusão: Este estudo, apesar de mostrar a maior presença de adenomas colorretais em indivíduos obesos, não mostrou diferença estatisticamente significativa na ocorrência de lesões pré-malignas.

Glutamine prevents oxidative stress in a model of portal hypertension.

AIM: To evaluate the protective effects of glutamine in a model of portal hypertension (PH) induced by partial portal vein ligation (PPVL). METHODS: Male Wistar rats were housed in a controlled environment and were allowed access to food and water ad libitum. Twenty-four male Wistar rats were divided into four experimental groups: (1) control group (SO) - rats underwent exploratory laparotomy; (2) control + glutamine group (SO + G) - rats were subjected to laparotomy and were treated intraperitoneally with glutamine; (3) portal hypertension group (PPVL) - rats were subjected to PPVL; and (4) PPVL + glutamine group (PPVL + G) - rats were treated intraperitoneally with glutamine for seven days. Local injuries were determined by evaluating intestinal segments for oxidative stress using lipid peroxidation and the activities of glutathione peroxidase (GPx), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) after PPVL. RESULTS: Lipid peroxidation of the membrane was increased in the animals subjected to PH (P < 0.01). However, the group that received glutamine for seven days after the PPVL procedure showed levels of lipid peroxidation similar to those of the control groups (P > 0.05). The activity of the antioxidant enzyme GTx was decreased in the gut of animals subjected to PH compared with that in the control group of animals not subjected to PH (P < 0.01). However, the group that received glutamine for seven days after the PPVL showed similar GTx activity to both the control groups not subjected to PH (P > 0.05). At least 10 random, non-overlapping images of each histological slide with 200 × magnification (44 pixel = 1 µm) were captured. The sum means of all areas, of each group were calculated. The mean areas of eNOS staining for both of the control groups were similar. The PPVL group showed the largest area of staining for eNOS. The PPVL + G group had the second highest amount of staining, but the mean value was much lower than that of the PPVL group (P < 0.01). For iNOS, the control (SO) and control + G (SO + G) groups showed similar areas of staining. The PPVL group contained the largest area of iNOS staining, followed by the PPVL + G group; however, this area was significantly smaller than that of the group that underwent PH without glutamine (P < 0.01). CONCLUSION: Treatment with glutamine prevents gut mucosal injury after PH in rats.

Effect of glutamine on liver injuries induced by intestinal ischemia-reperfusion in rats

INTRODUCTION: Intestinal ischemia-reperfusion (I/R) injury may cause cell and tissue damage, reaching also other organs such as the liver. Because of the involvement of free radicals in I/R injury, treatment options with antioxidants have been studied and tested. OBJECTIVE: To evaluate the effect of glutamine (Gln) in the liver of animals with intestinal I/R injury. METHODS: We used 20 male Wistar rats divided into four groups: sham-operated (SO); glutamine + sham-operated (G+SO); intestinal ischemia-reperfusion (I/R); glutamine + intestinal ischemia-reperfusion (G+I/R). The superior mesenteric artery was clamped for 30 minutes and reperfused for 15 minutes. Gln (25 mg/kg/day) diluted in 1 ml of saline was administered intraperitoneally on the two days before I/R induction. RESULTS: Levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), lipid peroxidation (LPO) and expressions of interleukin-6 (IL-6) and nuclear factor kappa B (NF-kB) showed a significant reduction in the G+I/R group as compared with the I/R group. The activity of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and the levels of glutathione (GSH) showed an increase in the G+I/R group as compared with the I/R group. CONCLUSION: Pretreatment with Gln reduced oxidative, tissue damage and showed a decrease expression of inflammatory mediators.

Effect of glutamine on liver injuries induced by intestinal ischemia-reperfusion in rats / Efecto de la glutamina en las lesiones hepáticas inducidas por isquemia-reperfusión intestinal en ratas

Introduction: Intestinal ischemia-reperfusion (I/R) injury may cause cell and tissue damage, reaching also other organs such as the liver. Because of the involvement of free radicals in I/R injury, treatment options with antioxidants have been studied and tested. Objective: To evaluate the effect of glutamine (Gln) in the liver of animals with intestinal I/R injury. Methods: We used 20 male Wistar rats divided into four groups: sham-operated (SO); glutamine + sham-operated (G+SO); intestinal ischemia-reperfusion (I/R); glutamine + intestinal ischemia-reperfusion (G+I/R). The superior mesenteric artery was clamped for 30 minutes and reperfused for 15 minutes. Gln (25 mg/kg/day) diluted in 1 ml of saline was administered intraperitoneally on the two days before I/R induction. Results: Levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), lipid peroxidation (LPO) and expressions of interleukin-6 (IL-6) and nuclear factor kappa B (NF-kB) showed a significant reduction in the G+I/R group as compared with the I/R group. The activity of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), and the levels of glutathione (GSH) showed an increase in the G+I/R group as compared with the I/R group. Conclusion: Pretreatment with Gln reduced oxidative, tissue damage and showed a decrease expression of inflammatory mediators (AU)

Introducción: las lesiones por isquemia-reperfusión (I/R) intestinales pueden causar daño celular y tisular, llegando incluso a otros órganos, como el hígado. Debido a la participación de radicales libres en la lesión I/R, se han estudiado y probado opciones de tratamiento con antioxidantes. Objetivo: evaluar el efecto de la glutamina (Gln) en el hígado de los animales con lesión intestinal I/R. Métodos: se utilizaron 20 ratas Wistar macho divididas en cuatro grupos: sham-operadas (SO); glutamina + sham-operadas (G+SO); isquemia-reperfusión intestinal (I/R); glutamina + isquemia-reperfusión intestinal (G+I/R). La arteria mesentérica superior se clampó durante 30 minutos y se llevó a cabo la reperfusión durante 15 minutos. Se adminsitró Gln (25 mg/kg/día) diluida en 1 ml de solución salina por vía intraperitoneal en los dos días previos a la inducción de la I/R. Resultados: los niveles de aspartato aminotransferasa (AST), alanina aminotransferasa (ALT) y fosfatasa alcalina (FA), la peroxidación lipídica (POL) y las expresiones de interleucina-6 (IL-6) y factor nuclear kappa B (NF-kB) mostraron una reducción significativa en el grupo G+I/R en comparación con el grupo I/R. La actividad de la catalasa (CAT), la superóxido dismutasa (SOD), glutatión peroxidasa (GPx), y los niveles de glutatión (GSH) mostraron un aumento en el grupo G+I/R en comparación con el grupo I/R. Conclusión: el tratamiento previo con Gln redujo el daño tisular oxidativo y mostró una disminución de los mediadores inflamatorios (AU)

Protective effect of glutamine on the main and adjacent organs damaged by ischemia-reperfusion in rats.

Intestinal ischemia and reperfusion (I/R) causes cellular and tissue damage to the intestine and remote organs such as the liver. Increased production of ROS and nitric oxide and dysregulation of cytoprotective enzymes may be involved in intestinal I/R. The aim was to evaluate the protective effects of glutamine on the intestine and liver of rats with intestinal I/R injury. Twenty male Wistar rats (300 g) were divided into four groups: sham-operated (SO), glutamine + SO (G + SO), I/R, and glutamine + I/R (G + I/R). Occlusion of the SMA for 30 min was followed by 15-min reperfusion. Glutamine (25 mg/kg/day) was administered once daily 24 and 48 h before I/R induction. Blood and tissue of were collected for aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, histopathological analysis, immunohistochemistry of IL-1ß and TNF-α, thiobarbituric acid reactive substance (TBARS) and nitric oxide, Nrf2/keap1, superoxide dismutase (SOD), NADPH quinone oxidoreductase1 (NQO1), inducible nitric oxide synthase (iNOS), heat shock protein (HSP70), glucose-regulated protein 78 (GRP78), and activating transcription factor 6 (ATF-6) by western blot. Statistic analysis by ANOVA-Student-Newman-Keuls test (mean ± SE) significantly was p < 0.05. Tissue damage, AST, ALT, IL-1ß, TNF-α, TBARS, NO, Keap1, iNOS, GRP78, and ATF-6 expression were significantly lower in the G + I/R group as compared to the I/R group. Expression of Nrf2, SOD, NQO1, and HSP70, was significantly higher in the G + I/R group as compared to I/R group. Pre-treatment with glutamine provided protection against oxidative damage in the intestine and liver in an experimental model of intestinal I/R.

Antioxidant effect of mesalazine in the experimental colitis model induced by acetic acid / Efeito antioxidante da mesalazina no modelo de colite experimental induzida por ácido acético

Abstract Introduction Inflammatory bowel disease (IBD) is characterized by a chronic inflammation of the gastrointestinal tract, without specific cause or pathogen. Objective The effect of mesalazine in a colitis model induced by acetic acid (AA) was evaluated. Methods We used 40 Wistar rats, ±350 g, divided into 4 groups: control (CO); control + mesalazine (CO + M); colitis (CL) and colitis + M (CL + M) at 24 and 48 h of treatment. The animals received the substances by an intracolonic enema of AA 4% and treatment with mesalazine PO 20 mg/kg after colitis induction. Results Mesalazine reduced tissue damage in the gut, normalized sphincter anal pressure levels and decreased lipid peroxidation, metabolites of nitric oxide and iNOS and NF-kB expression in the treated groups in both treatment time points (24 and 48 h), as well as the activity of antioxidant enzymes. Conclusion Mesalazine was effective in reducing tissue damage and oxidative and inflammatory damage, restored antioxidant capacity and increased anal sphincter pressure levels, possibly due to its antioxidant effect.

Resumo Introdução A doença inflamatória intestinal (DII) caracteriza-se por uma inflamação crônica do trato gastrointestinal sem uma causa ou patógeno específico. Objetivo Foi avaliado o efeito da mesalazina no modelo de colite induzida por ácido acético (AA). Material e métodos Foram utilizados 40 ratos wistar, ±350 gramas, divididos em 4 grupos: Controle (CO); Controle + Mesalasina (CO + M); Colite (CL) e Colite + M (CL + M) nos tempos de 24 e 48 horas de tratamento. Os animais foram submetidos à administração intracolônica por enema com solução de AA a 4% e tratamento com mesalazina na dose oral de 20 mg/kg após a indução da colite. Resultados A mesalazina reduziu as lesões teciduais no intestino, normalizou os níveis de pressão anal esfincteriana, reduziu a lipoperoxidação, metabólitos do óxido nítrico e expressão da iNOS e do NF-kB nos grupos tratados em ambos os tempos de tratamento (24 e 48 horas), bem como a atividade das enzimas antioxidantes. Conclusão A mesalazina demonstrou eficácia na redução das lesões teciduais, danos oxidativos e inflamatórios, restabeleceu a capacidade antioxidante e aumentou os níveis de pressão anal esfincteriana, possivelmente pelo seu efeito antioxidante.

Effect of lecithin on oxidative stress in an experimental model of rats colitis induced by acetic acid / Efeito da lecitina sobre o estresse oxidativo no modelo experimental de colite induzida por ácido acético em ratos

Ulcerative colitis (UC) is an inflammatory disease that affects the bowels. Reactive oxygen species (ROS) are involved in the progress of UC. Objective: Evaluate the antioxidant effect of lecithin in an experimental model of acute UC induced by administration of acetic acid (AA) in rats. Methods: Lecithin (0.5 mL/kg/day) administered orally 2 days before and after induction of colitis with 4% AA in a volume of 4 mL. Twenty-five male Wistar rats were divided in 5 groups: control (CO); control + lecithin (CO + LE); colitis (CL); colitis + lecithin (CL + LE); lecithin + colitis (LE + CL). Anal sphincter pressure, LPO (TBARS), and antioxidant activity of enzymes superoxide dismutase (SOD) and catalase (CAT) were measured, and a histological analysis with H&E was performed. Results and discussion: Anal sphincter pressure was significantly smaller in the CO group, lecithin treatment increased it in pre- and post-treated groups. LPO and SOD activity were increased in the CO group and decreased in the lecithin-treated groups. CAT activity was increased in CO group and decreased in lecithin groups. The histological analysis showed damage to the bowels with destruction of crypts, edema, and inflammatory infiltrate. Use of lecithin preserved the crypts and decreased the edema. Conclusion: Ulcerative colitis increased lipid peroxidation, and the use of lecithin was effective reducing damage to the bowels in the model of experimental colitis.

A retocolite ulcerativa (RCUI) é uma doença intestinal inflamatória. Espécies reativas de oxigênio (ERO) estão envolvidas no progresso da RCUI. Objetivo: Avaliar o efeito antioxidante de lecitina em modelo experimental de RCUI induzida pela administração de ácido acético (AA) em ratos. Métodos: A Lecitina (0,5 mL/kg/dia) foi administrada por via oral 2 dias antes e após a indução de colite com AA. Vinte e cinco ratos Wistar machos foram divididos em 5 grupos: controle (CO); controle + lecitina (CO + LE); colite (CL); colite + lecitina (CL + LE); lecitina + colite (LE + CL). Foram avaliadas: pressão do esfíncter anal, lipoperoxidação (LPO), atividade antioxidante das enzimas superóxido dismutase (SOD) e catalase (CAT), e foi realizada uma análise histológica com H&E. Resultados e discussão: A pressão do esfíncter anal foi significativamente menor no grupo CL, o tratamento com lecitina aumentou a pressão nos grupos pré e pós tratados. A LPO e atividade da SOD aumentaram no grupo CL e diminuíram nos grupos tratados com lecitina. A atividade da CAT foi aumentada no grupo CL e diminuiu nos grupos com lecitina. A análise histológica mostrou danos ao intestino com destruição das criptas, edema e infiltrado inflamatório. O uso de lecitina proporcionou uma preservação das criptas e diminuição do edema. Conclusão: A RCUI aumenta a LPO, a utilização de lecitina foi eficaz na redução dos danos ao intestino induzido por AA no modelo de colite experimental.

Obesity depresses the anti-inflammatory HSP70 pathway, contributing to NAFLD progression.

OBJECTIVES: To evaluate whether reduced activity of the anti-inflammatory HSP70 pathway correlates with nonalcoholic fatty liver disease (NAFLD) progression and with markers of oxidative stress because obesity activates inflammatory JNKs, whereas HSP70 exerts the opposite effect. METHODS: Adult obese patients (N = 95) undergoing bariatric surgery were divided into steatosis (ST), steatohepatitis (SH), and fibrosis (SH+F) groups. The levels of HSP70, its major transcription factor, HSF1, and JNKs were assessed by immunoblotting hepatic and visceral adipose tissue; data were confirmed by immunohistochemistry. Plasma biochemistry (lipids, HbA1c , HOMA, hepatic enzymes, and redox markers) was also evaluated. RESULTS: In both liver and adipose tissue, decreased HSP70 levels, paralleled by similar reductions in HSF1 and reduced plasma antioxidant enzyme activities, correlated with insulin resistance and with NAFLD progression (expression levels were as follows: ST > SH > SH + F). The immunohistochemistry results suggested Kupffer cells as a site of HSP70 inhibition. Conversely, JNK1 content and phosphorylation increased. CONCLUSIONS: Decreased HSF1 levels in the liver and fat of obese patients correlated with impairment of HSP70 in an NAFLD stage-dependent manner. This impairment may affect HSP70-dependent anti-inflammation, with consequent oxidative stress and insulin resistance in advanced stages of NAFLD. Possible causal effects of fat cell senescence are discussed.