Local Application of Tacrolimus in Distal Colitis: Feasible and Safe

Background: Tacrolimus is a potent immunomodulator that is effective in the systemic treatment of inflammatory bowel diseases (IBD). However, potential toxicity and systemic (side) effects after oral intake limit its use. We investigated the local applicability and Safety of tacrolimus for distal colitis. Methods: Patients; with refractory left-sided colitis or proctitis were treated for 4 weeks with a daily tacrolimus 2-4 mg enema or 2 mg suppository. Safety of local tacrolimus treatment was assessed by measurement of whole blood tacrolimus trough levels by monitoring liver and kidney function and blood glucose levels. Efficacy of treatment was assessed by comparing the disease activity index (DAI) in ulcerative colitis (UC) patients and endoscopic and histologic appearances before and after 4 weeks of treatment. Results: Nineteen patients with left-sided colitis (n = 7) or proctitis (n 12) were treated. Two patients with left-sided colitis had Crohn's disease (Cl)), the other 17 patients had UC. None of the patients developed side effects. Blood trough levels of tacrolimus were too low to induce systemic immune Suppression. Thirteen of 19 patients (3/5 left-sided UC, 0/2 left-sided CD, and 10/12 proctitis) showed clinical improvement of disease activity after 4 weeks of local tacrolimus treatment. Moreover, a significant improvement of histological appearance was observed in the suppository-treated group. Conclusions: This study demonstrates that local colonic application of tacrolimus 2-4 mg daily in patients with refractory distal colitis is Feasible, probably safe, and potentially efficacious, and therefore opens the need for a further, randomized trial

Época da indução e evocação floral em Citrus sinensis (L.) Osbeck cv. Pêra Rio The flower induction and evocation period in Citrus sinensis (L.) Osbeck cv. Pêra Rio

A produção do estímulo floral (indução) e emissão das primeiras sépalas, na gema floralmente determinada (evocação floral) em Citrus sinensis (L.) Osbeck cv. Pêra Rio pôde ser acompanhada pelas variações anatômicas nos meristemas apicais e axilares. Com objetivo de determinar a época na qual ocorre a indução e evocação floral, cortes longitudinais de gemas apicais e axilares, corados com pironina Y-methylgreen foram efetuados em períodos regulares de maio a agosto. Através das mudanças no formato da gema, principalmente diâmetro, que aumentou com a indução, foi possível determinar a época do ano na qual gemas vegetativas são induzidas a florescerem. Foram detectadas variações nos diâmetros das gemas no período de início da morfogênese floral (meados até o final de julho). A medição do diâmetro das gemas mostra-se um procedimento eficiente para acompanhar os fenômenos decorrentes da indução, evocação e morfogênese florais. Gemas vegetativas apresentam diâmetro médio de 100µm, com túnica composta por três camadas, de formato cônico, recobrindo o corpo, ao passo que a reprodutiva é mais achatada, após a iniciação do primeiro primórdio de sépala, exibindo diâmetro médio de 200µm. Coloração com pironina Y-methylgreen proporciona a captação do fenômeno da evocação floral, pela detecção de regiões mais concentradas em RNA, nas zonas periféricas das gemas; alteração bioquímica esta que precede a emissão das sépalas.<br>The research aims to determine the time in which the inflorescence induction and evocation occurs. The production of inflorescence stimulus (induction) and emission of first sepals in a bud determined as a flower bud (floral evocation) in Citrus sinensis (L.) Osbeck cv. Pêra Rio could be observed through the anatomic variations of the apical and lateral meristems. Longitudinal sections, stained with pironina Y-methylgreen were done in regular periods from May to August. The time of the year in which the vegetative buds are induced to blossom was determined through the bud shape changes, chiefly considering the diameter, which has increased with the induction. Bud diameter variations were detected on the second half of July, the period of floral morphogenesis incipience. The measurement of the bud diameter is an efficient procedure to follow up the phenomena originated from the floral induction, evocation and morphogenesis. Vegetative buds bring out an average diameter of 100µm with a three-layer tunic in a conic shape, recovering its body. The reproductive bud, in turn, is flatter, after the initiation of the first sepal primordium, showing an average diameter of 200µm. The pironina Y-methylgreen stain provides the observation of the floral evocation phenomenon, through the detection of regions with a higher RNA level, in the bud external areas. This biochemical alteration precedes the sepal emission