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.

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.

Bone healing around titanium implants in two rat colitis models

Objective: Crohn's disease is a chronic inflammatory process that has recently been associated with a higher risk of early implant failure. Herein we provide information on the impact of colitis on peri-implant bone formation using preclinical models of chemically induced colitis. Methods: Colitis was induced by intrarectal instillation of 2,4,6-trinitro-benzene-sulfonic-acid (TNBS). Colitis was also induced by feeding rats dextran-sodium-sulfate (DSS) in drinking water. One week after disease induction, titanium miniscrews were inserted into the tibia. Four weeks after implantation, peri-implant bone volume per tissue volume (BV/TV) and bone-to-implant contacts (BIC) were determined by histomorphometric analysis. Results: Cortical histomorphometric parameters were similar in the control (n = 10), DSS (n = 10) and TNBS (n = 8) groups. Cortical BV/TV was 92.2 ± 3.7%, 92.0 ± 3.0% and 92.6 ± 2.7%. Cortical BIC was 81.3 ± 8.8%, 83.2 ± 8.4% and 84.0 ± 7.0%, respectively. No significant differences were observed when comparing the medullary BV/TV and BIC (19.5 ± 6.4%, 16.2 ± 5.6% and 15.4 ± 9.0%) and (48.8 ± 12.9%, 49.2 ± 6.2 and 41.9 ± 11.7%), respectively. Successful induction of colitis was confirmed by loss of body weight and colon morphology. Conclusions: The results suggest bone regeneration around implants is not impaired in chemically induced colitis models. Considering that Crohn's disease can affect any part of the gastrointestinal tract including the mouth, our model only partially reflects the clinical situation. © 2012 John Wiley & Sons A/S.

Anti-inflammatory intestinal activity of Arctium lappa L. (Asteraceae) in TNBS colitis model

Ethnopharmacological relevance: In Brazilian traditional medicine, Arctium lappa (Asteraceae), has been reported to relieve gastrointestinal symptoms. Aim of the study: In the present study, we investigated the effects of the lactone sesquiterpene onopordopicrin enriched fraction (ONP fraction) from Arctium lappa in an experimental colitis model induced by 2,4,6 trinitrobenzene sulfonic acid and performed experiments to elucidate the underlying action mechanisms involved in that effect. Materials and methods: ONP fraction (25 and 50 mg/kg/day) was orally administered 48, 24 and 1 h prior to the induction of colitis and 24 h after. The inflammatory response was assessed by gross appearance, myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-α) levels and a histological study of the lesions. We determined cyclooxygenase (COX)-1 and -2 protein expressions by western blotting and immunohistochemistry assays. Results: TNBS group was characterized by increased colonic wall thickness, edema, diffuse inflammatory cell infiltration, increased MPO activity and TNF-α levels. On the contrary, ONP fraction (25 and 50 mg/kg) treatment significantly reduced the macroscopic inflammation scores (p<0.05 and p<0.01, respectively) and morphological alterations associated with an increase in the mucus secretion. Similarly, the degree of neutrophil infiltration and the cytokine levels were significantly ameliorated. Moreover, COX-2 expression was up regulated in TNBS-treated rats. In contrast, ONP fraction (50 mg/kg) administration reduced COX-2 overexpression. Conclusions: We have shown that the ONP fraction obtained from Arctium lappa exert marked protective effects in acute experimental colitis, confirming and justifying, at least in part, the popular use of this plant to treat gastrointestinal diseases. © 2013 Elsevier B.V. All rights reserved.

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)

Atividade antimicrobiana in vitro de extratos hidroetanólicos de Astronium sp incorporados ou não em sistemas nanoestruturados

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito dos extratos metanólicos das folhas de Davilla elliptica e Davilla nnitida na vigência de colite experimental induzida por ácido trinitrobenzenosulfônico em ratos

Pós-graduação em Ciências Biológicas (Farmacologia) - IBB