Chronic administration of Abarema cochliacarpos attenuates colonic inflammation in rats

Inflammatory bowel diseases are characterized by a chronic clinical course of relapse and remission associated with self-destructive inflammation of the gastrointestinal tract. Active extracts from plants have emerged as natural potential candidates for its treatment. Abarema cochliacarpos (Gomes) Barneby & Grimes, Fabaceae (Barbatimão), is a native medicinal plant in to Brazil. Previously we have demonstrated in an acute colitis model a marked protective effect of a butanolic extract, so we decided to assess its anti-inflammatory effect in a chronic ulcerative colitis model induced by trinitrobenzensulfonic acid (TNBS). Abarema cochliacarpos (150 mg/day, v.o.) was administered for fourteen consecutive days. This treatment decreased significantly macroscopic damage as compared with TNBS. Histological analysis showed that the extract improved the microscopic structure. Myeloperoxidase activity (MPO) was significantly decreased. Study of cytokines showed that TNF-α was diminished and IL-10 level was increased after Abarema cochliacarpos treatment. In order to elucidate inflammatory mechanisms, expression of cyclooxygenase (COX)-2 and nitric oxide synthase (iNOS) were studied showing a significant downregulation. In addition, there was reduction in the JNK and p-38 activation. Finally, IκB degradation was blocked by Abarema cochliacarpos treatment being consistent with an up-regulation of the NF-kappaB-binding activity. These results reinforce the anti-inflammatory effects described previously suggesting that Abarema cochliacarpos could provide a source for the search for new anti-inflammatory compounds useful in ulcerative colitis treatment.

OBTENCAO DE MESALAZINA (5-ASA) POR CARBOXILACAO DE P-AMINOFENOL

The 5-aminosalicylic acid is usually prepared: 1. by the reduction of the azodye from diazotized aniline and salicylic acid and the posterior reduction of the formed compound; 2. for carboxylation with carbon dioxide under high pressure of p-aminophenol. Both do not present high yield, but the carboxylation process of p-aminophenol can easily be used and can reduce the obtainment process of 3 steps to only 2. Another advantage of this process is the fact that the product is produced without contaminants, because only one solid reagent (p-aminophenol) and the agent of carboxylation (CO2) is used.

Indices de atividade da doença inflamatória do intestino: indicadores clínicos e laboratoriais.

The quantification of the degree of activity of inflammatory bowel disease is assuming growing importance nowadays. The activity index of the disease can be attained by clinical and laboratorial indicators. For ulcerative colitis the mostly used clinical parameters are daily bowel movements and presence of bloody diarrhea whereas albumin, hemoglobin, ESR and positive acute phase protein measurements are the laboratory parameters. For Crohn's disease activity besides the daily bowel movements the presence of abdominal pain and discomfort sensation are also frequently used whereas the C-reactive protein is the most used laboratory test which is able to detect the disease reactivation even before the appearance of any clinical sign. The combinations of clinical signs with the laboratory tests earned the sympathy of the specialists and the set of ensembled indicators has been recognized by the author's name. In this sense, the classification of the ulcerative colitis activity originally proposed by Truelove and Witts deserves presently a wide acceptance whereas such agreement is still lacking for Crohn's disease activity. In the mean time, the Bristol index is clinically the most feasible, once the Crohn's disease activity index and the Van Hees index are considered too complex. However the latter indexes are still useful mainly for comparisons among multicentric data. It seems that the currently existing clinical signs used for Crohn's disease activity would be quantitatively improved by adding some easily made laboratory tests such as C-reactive protein.

Reativação da retocolite ulcerativa com o uso de droga anti-inflamatória não esteróide: relato de caso e revisão da literatura

The case of a patient with ulcerative colitis and isolated sacro-ileitis is presented. She suffered reactivation of the intestinal disease with diclofenac. The patient was allergic to sulfasalazine and was using fish oil fatty acid. The possible mechanisms of reactivation of the inflammatory bowel disease with non-steroidal anti-inflammatory drugs are discussed. It is suggested when necessary the utilization of non-steroidal anti-inflammatory drugs that inhibits the lipoxygenase in these patients.

Utilização do metabolismo protéico ( 15N-glicina) na detecção precoce de agravamento da atividade da doença em pacientes portadores de retocolite ulcerativa inespecífica

Disease activity was assessed in 10 (five males and five females) ulcerative colitis patients through the following parameters: clinical, laboratory, sigmoidoscopic and histological. Protein metabolism was also assessed with 15N-glycine and urinary ammonia as end product. Only one patient had exacerbation of the disease two months after the study started. This patient presented in the beginning of the study protein synthesis and breakdown of 4.51 and 3.47 g protein/kg/day, respectively, values higher than all other patients, showing an hypermetabolic state, suggesting an increase of the disease activity. However, this increase was not detected by others indicators and indexes utilised. These data allow to suggest the hypothesis that protein metabolism predicts precociously the exacerbation of disease activity in ulcerative colitis patients.

Advances in prodrug design

The background of prodrug design is presented herein as the basis for introducing new and advanced latent systems, taking into account mainly the versatility of polymers and other macromolecules as carriers. PDEPT (Polymer-Directed Enzyme Prodrug Therapy); PELT (Polymer-Enzyme Liposome Therapy); CDS (Chemical Delivery System); ADEPT(Antibody-Directed Enzyme Prodrug Therapy); GDEPT/VDEPT (Gene-Directed Enzyme Prodrug Therapy/Virus-Directed Enzyme Prodrug Therapy); ODDS (Osteotropic Drug Delivery System) and LEAPT (Lectin-directed enzyme-activated prodrug therapy) are briefly described and some examples are given. © 2005 Bentham Science Publishers Ltd.

Infliximabe no tratamento inicial da retocolite ulcerativa moderada e grave. Terapia top down: Relato preliminar

The first option for the treatment of UC is both: salicylates or corticoids. Recently, in late November of 2006, the Brazilian Ministry of Health has approved infliximab (Remicade c, Mantecorp, Brazil) to treat ulcerative colitis. We report the use of infliximab as a first option for the treatment of two patients with severe ulcerative colitis. Case report: Patient 1: AZF, 52 years-old, female, was first diagnosed with UC after history and clinical examination; colonoscopy showed pancolitis with positive biopsy (crypt microabscess). Her Mayo score was 10 (range: 0 to 12/asymptomatic to severe colitis). She received intra venous infusion of infliximab at a dose of 5mg/Kg of body weigh at week 0, 2, 6 and 14. Then, patient was given mesalazine 4.5 g/day for maintenance therapy. Clinical response was defined as a decreased from baseline in the total Mayo score of at least 3 points. At present, patient is asymptomatic with Mayo score of 3 one moth after the last dose of infliximab. Patient 2: MLA, 45 years-old, female was first diagnosed with bloody diarrhea; colonoscopy showed left colitis and the biopsy was positive for ulcerative colitis. Her Mayo score was 9. She was offered and accepted the step down treatment. She was given infliximab 5mg/Kg of body weight at week 0, 2, 6 and 14. After initial treatment with infliximab, she received mesalazine 4.2 g/day. At present, she is asymptomatic with Mayo score of 2 eighteen days after the last dose of infliximab. At our knowledge, this is the first Brazilian report of the use of infliximab as fist-line therapy in ulcerative colitis. Few days after the begging of the infusion, an impressive clinical and colonoscopy improvement was seen in these two patients. Recently, it has been reported the use of infliximab as first-line therapy in pediatric Crohn disease. Infliximab could be a good option in cases of moderate and severe UC to avoid the side effects of the use of high doses of corticoids in patients with moderate and severe UC. However, the question if step-down therapy in ulcerative colitis is better then conventional therapy with salicylates and corticoids needs to be answered by randomized trials.

Aparecimento de psoríase durante o tratamento das doenças inflamatórias intestinais com infliximabe: A terapia biológica deve ser suspensa?

Context - Several paradoxical cases of infliximab-induced or-exacerbated psoriatic lesions have been described in the recent years. There is disagreement regarding the need to discontinue infliximab in order to achieve the resolution of these adverse cutaneous reactions specifically in inflammatory bowel disease (IBD) patients. Objective - To systematically review the literature to collect information on IBD patients that showed this adverse cutaneous reaction, focusing mainly on the therapeutic approach. Methods - A systematic literature review was performed utilizing Medline, Embase, SciELO and Lilacs databases. Published studies were identified, reviewed and the data were extracted. Results - Thirty-four studies (69 IBD patients) met inclusion criteria for review. There was inconsistency in reporting of some clinical and therapeutic aspects. Most patients included had Crohn's disease (89.86%), was female (47.83%), had an average age of 27.11 years, and no reported history of psoriasis (84.05%). The patients developed primarily plaque-type psoriasis (40.58%). There was complete remission of psoriatic lesions in 86.96% of IBD patients, existing differences in the therapeutic approaches; cessation of infliximab therapy led to resolution in 47.83% of cases and 43.48% of patients were able to continue infliximab therapy. Conclusion - As increasing numbers of IBD patients with psoriasis induced or exacerbated by infliximab, physicians should be aware of its clinical manifestations so that appropriate diagnosis and treatment are properly established. The decision whether to continue or discontinue infliximab should be individualized.

Avaliação da atividade da fibra alimentar de Typha angustifolia L. e des seus efeitos sinérgicos com a prednisolona no modelo de colite ulcerativa induzida por ácido trinitrobenzenosulfônico em ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Avaliação da atividade preventiva da dieta enriquecida com banana verde (banana 'Nanica' Musa sp AAA) e de seus efeitos sinérgicos com a prednisolona no modelo de colite ulcerativa induzida por ácido trinitrobenzenosulfônico em ratos

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Atividade anti-inflamatória intestinal do extrato padronizado de Physalis angulata L. (camapú)

Pós-graduação em Ciências Biológicas (Farmacologia) - IBB

Efeitos do extrato de Baccharis dracunculifolia DC em diferentes mediadores da inflamação intestinal induzida por TNBS em ratos

Pós-graduação em Ciências Biológicas (Farmacologia) - IBB

HSP70, heparanase e HPRT participam da resposta inflamtória intestinal induzida por TNBS em ratos

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Efeito da (-)-epicatequina presente nas folhas Mouriri pusa Gardin. (Melastomataceae) na prevenção e tratamento de colite ulcerativa em ratos

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação do estado nutricional, ingestão de antioxidante e extensão da lesão intestinal em pacientes portadores de colte ulcerativa

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)