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- New pharmacological approach for inflammatory bowel diseasePublication . Silva, Inês; Pinto, Rui; Mateus, VanessaInflammatory bowel disease includes Crohn's disease and ulcerative colitis. Chronic inflammatory disease of the gastrointestinal (GI) tract is characterized by recurrent ulceration. IBD affects 7–10% of people worldwide, mainly of Caucasian descent. It manifests into several intestinal and extra-intestinal symptoms, mainly related to oxidative stress, inflammation, and autoimmune reaction. Aim of the study: evaluate the influence of a new pharmacological approach with erythropoietin in the establishment and development of inflammation associated with IBD, through of an experimental colitis model in rodents.
- TNBS-induced colitis in rodents: preliminary results of a chronic modelPublication . Silva, Inês; Mateus, Vanessa; Pinto, RuiBackground: Inflammatory bowel disease (IBD) is a gastrointestinal disorder characterized by chronic inflammation of the intestinal epithelium. The symptoms of IBD depend on the intestinal affected segment and usually include diarrhea often with blood, colic abdominal pain, and fecal urgency. Beyond these, other unspecific symptoms may occur like fever, loss of appetite and weight, fatigue, and primary amenorrhea. Nowadays, used therapy in IBD consists of salicylates, corticosteroids, immunosuppressants, and biological therapy. These drugs aim to induce and/or maintain the patient in remission and ameliorate the disease’s secondary effects, rather than modifying or reversing the underlying pathogenic mechanism. Aim: Development of an animal model of trinitrobenzene sulfonic acid (TNBS)-induced chronic colitis in order to evaluate the influence of new drugs in the IBD.
- Potencial da genisteína na reativação da expressão do gene da γ-globulina e indução da hemoglobina fetalPublication . Matos, Elisabete; Sousa, Daniela; Delgadinho, Mariana; Mateus, Vanessa; Silva, Inês; Ribeiro, Edna; Brito, MiguelProject goals: Identification of novel agents with higher HbF inducing activity and lower cytotoxicity accessible in low-income countries, has been one of the major challenges over the past few years. A naturally occurring isoflavone found in plant products ( lentils, and chickpeas). Potent inhibitor of the PTK and topoisomerase II G 2 /M cell cycle arrest) regulates MAPK pathways (p 38 MAPK and ERK 1 /ERK 2. Antioxidant, antineoplastic, antihelmintic antiangiogenic, and immunosuppressive properties. Structurally similar to estrogen (estradiol 17 β). Potential to mimic, enhance, or impair the estradiol biosynthesis pathway with high reported binding selectivity for ER β isoform.
- O potencial da epigalocatequina-3-galato na reativação da expressão da y-globina e indução da hemoglobina fetalPublication . Sousa, Daniela; Matos, Elisabete; Delgadinho, Mariana; Ribeiro, Edna; Mateus, Vanessa; Silva, Inês; Brito, MiguelAs hemoglobinopatias estão entre as doenças genéticas mais comuns em todo o mundo, particularmente a doença falciforme (DF) e a β talassemia e são causadas por defeitos na estrutura da hemoglobina ou na expressão dos genes da globina durante a transição de hemoglobina fetal HbF pela hemoglobina adulta HbA. Novas abordagens terapêuticas estão a ser desenvolvidas para irem além do tratamento paliativo que impõe altos custos aos sistemas de saúde. Desta forma, uma terapia alternativa mais acessível e promissora é a indução farmacológica de HbF. A elevação da síntese da cadeia γ-globina fetal equilibra o excesso da cadeia α globina pela formação de HbF modulando a anemia severa nos pacientes com β talassemia maior e inibindo diretamente a polimerização da hemoglobina falciforme em pacientes com DF. A hidroxiureia (HU) é o único medicamento aprovado pela FDA para o tratamento de pacientes com DF e com β talassemia intermédia. No entanto, este fármaco inibe a replicação do ADN e a possibilidade de ser mutagénico e carcinogénico limita o seu uso clínico. Por este motivo, o desenvolvimento de novos compostos indutores de HbF com alta eficiência e menor toxicidade, estão a ser investigados. Os compostos biológicos da dieta, como a epigalocatequina galato (EGCG) estão associados a efeitos benéficos para a saúde devido aos seus efeitos anti inflamatórios e antioxidantes. A EGCG é a catequina mais abundante no chá verde e a sua propriedade anti inflamatória desempenha um papel crucial na regulação da expressão e transcrição relativa de genes. O objetivo deste projeto foi avaliar o potencial da EGCG, na reativação da expressão do gene da γ-globina e, deste modo, na indução de HbF.
- TNBS-induced colitis in rodents: preliminary results of a chronic modelPublication . Silva, Inês; Solas, João; Sousa, Mariana; Modesto, Rita; Mateus, Vanessa; Pinto, RuiChronic inflammatory disease of the gastrointestinal (GI) tract characterized by recurrent ulceration. Treatment of inflammatory bowel disease induce and maintain the patient in remission However do not modify or reverse the underlying pathogenic mechanism. Nonclinical studies for emerging therapeutic strategies. Aim of the study: Evaluate the efficacy of new drugs in inflammatory bowel disease through an animal model of TNBS-induced chronic colitis.
- Preclinical study in vivo for new pharmacological approaches in inflammatory bowel disease: a systematic review of chronic model of TNBS-induced colitisPublication . Silva, Inês; Pinto, Rui; Mateus, VanessaThe preclinical studies in vivo provide means of characterizing physiologic interactions when our understanding of such processes is insufficient to allow replacement with in vitro systems and play a pivotal role in the development of a novel therapeutic drug cure. Chemically induced colitis models are relatively easy and rapid to develop. The 2,4,6-trinitrobenzenesulfonic acid (TNBS) colitis model is one of the main models in the experimental studies of inflammatory bowel disease (IBD) since inflammation induced by TNBS mimics several features of Crohn’s disease. This review aims to summarize the existing literature and discuss different protocols for the induction of chronic model of TNBS-induced colitis. We searched MEDLINE via Pubmed platform for studies published through December 2018, using MeSH terms (Crohn Disease.kw) OR (Inflammatory Bowel Diseases.kw) OR (Colitis, Ulcerative.kw) AND (trinitrobenzenesulfonic acid.kw) AND (disease models, animal.kw) AND (mice.all). The inclusion criteria were original articles, preclinical studies in vivo using mice, a chronic model of colitis, and TNBS as the inducer of colitis and articles published in English. Chronic TNBS-induced colitis is made with multiple TNBS intrarectal administrations in an average dose of 1.2 mg using a volume lower than 150 μL in 50% ethanol. The strains mostly used are Balb/c and C57BL/6 with 5–6 weeks. To characterize the preclinical model the parameters more used include body weight, stool consistency and morbidity, inflammatory biomarkers like interferon (IFN)-γ, myeloperoxidase (MPO), tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-10, presence of ulcers, thickness or hyperemia in the colon, and histological evaluation of the inflammation. Experimental chronic colitis is induced by multiple rectal instillations of TNBS increasing doses in ethanol using Balb/c and C57BL/6 mice.