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Resume Objectif Chercher s’il y a une relation entre les concentrations de 6-thioguanine nucleotide et des 6-methyl mercaptopurine et l’efficacite clinique et les effets indesirables a travers une population de patients atteints de maladie inflammatoire chronique de l’intestin. Methodes Nous incluons des patients atteins de la maladie de Crohn ou de rectocolite hemorragique (RCH) traites par l’azathioprine pendant une duree minimale de 12 mois. Pour chaque patient, un dosage des metabolites a ete realise. Resultats Nous avons inclus 43 patients atteints de maladie de Crohn et 7 de RCH. L’azathioprine a ete indiquee pour une cortico-dependance dans 23 cas, pour prevenir les recidives post-operatoires dans 10 cas, pour maintenir une remission clinique obtenue par un traitement medical chez 17 patients. Conclusion Notre travail confirme la relation entre la concentration de la 6TGN et la survenue d’une myelo-toxicite.

Introduction In recent years, many marine resources have drew attention in the research for bio-active compounds to develop new drugs and health foods. (1) Marine algae are now considered as a rich source of antioxidants (2). It is known that seaweeds contain numerous bioactive substances that have the ability to lower cholesterol, reduce blood pressure, promote healthy digestion; and antioxidant activity (3). Natural antioxidants are interesting compounds due to their properties which help prevent oxidative stress (4), among other potentially beneficial actions. For instance, several biological effects have been attributed to flavonoids, such as anti-tumoral, anti-inflammatory, anti-ischemic and anti-aggregate plaquetary activities. These activities are believed to be in part related to the antioxidant properties of the compounds, namely in scavenging radical oxygen species (ROS). (5, 6) The cold ischemia constitute a situation of oxidative stress in touch with liberation of oxygenated radicals, these situations incited the researchers to find means for the improvement of the conservation of organs allowing to prolong the durations of the cold ischemia of certain organs (in particular the liver) with conservation of the maximum functional value. However, the constant efforts led by the teams of transplantation to develop transplants, the conservation of organs remains a problem to be resolved. (7) Conservation solution of organ appears as being a stemming to remedy the fatal effects of the ischemia-reperfusion. For our part, we think that seaweeds have not delivered their secrets and yet especially that the marine environment of the Tunisian coast still remains little exploited in spite of the big variety of the fauna and the flora of the coast. We envisage in this work, to study a sort of seaweed collected on the Tunisian quotation in the region of "Chott Meriem" (North West of Tunisia). The purpose of our work is to estimate the capacity of extracts stemming from the green seaweed Ulva lactuca to improve the conservation solution of organs against the hepatic effects of ischemia.

During last years, significant progress was made in the comprehension of the hepatic lesions after Ischemia-Reperfusion episode in order to improve the Results in practice clinical.To avoid or reduce the damage induced by Ischemia-Reperfusion, we developed a model of hepatic Ischemia-Reperfusion with variable periods of reperfusion from 0 to 24 hours. Our study related to rats Wistar males. Six various groups were studied: the first reference group (without neither ischemia and reperfusion), the second group with ischemia of 90 min and without reperfusion and the 3end , 4end, 5end and 6end groups in addition to ischemia, underwent a reperfusion of 30 min, 2h, 6h and 24h respectively. The damage of hepatic Ischemia-Reperfusion was evaluated by a biochemical test based on the proportioning of transaminases and an anatomopathologic study by optical microscopy for the determination of the degree of hepatic attack. The RESULTS obtained seem to show an aggravation of the liver lesions and an increase in the plasmatic rates of AST and ALT in relation with the duration of the reperfusion. Indeed, the maximum of damage was observed after 2 hours of reperfusion. We observed a reduction in the lesions after 6h and 24h of reperfusion. Our work enabled us to describe a simple model of hepatic Ischemia-Reperfusion with functional, biochemical and anatomopathologic tests.

The objective of our work is to search if there is a relation between azathioprine's metabolites (6-thioguanines nucleotides and 6-methyl mercaptopurines) and clinical efficacy and adverse effects of azathioprine in inflammatory bowel disease population.We included patients with Crohn's disease or ulcerative colitis (UC) treated by azathioprine for a duration more than 1year. Each patient had a dosage of azathioprine metabolites.We included 43 Crohn's disease patients and 7 UC. Azathioprine was indicated for steroid dependancy in 23 cases, to prevent post-operative recurrence in 10 cases, to maintain clinical remission obtained by medical treatment in 17 patients. A clinical response to azathioprine (obtention of remission, absence of recurrence during the follow up) was observed in 34 patients.Our work confirms the relation between the doses of azathioprine metabolites and the myelotoxicity due to this molecule.

The objective of our work is to search if there is a relation between azathioprine's metabolites (6-thioguanines nucleotides and 6-methyl mercaptopurines) and clinical efficacy and adverse effects of azathioprine in inflammatory bowel disease population.We included patients with Crohn's disease or ulcerative colitis (UC) treated by azathioprine for a duration more than 1 year. Each patient had a dosage of azathioprine metabolites.We included 43 Crohn's disease patients and 7 UC. Azathioprine was indicated for steroid dependancy in 23 cases, to prevent post-operative recurrence in 10 cases, to maintain clinical remission obtained by medical treatment in 17 patients. A clinical response to azathioprine (obtention of remission, absence of recurrence during the follow up) was observed in 34 patients.Our work confirms the relation between the doses of azathioprine metabolites and the myelotoxicity due to this molecule.

Summary Aim The aim of this study was to determine the frequencies of TPMT and ITPA polymorphisms in Crohn's disease patients of Tunisian origin and to compare them with allele frequencies previously reported in other populations of various ethnic origins. Methods ITPA (c.94C>A and IVS2+21A>C) and TPMT (c.238G>C, c.460G>A and c.719A>G) mutations and genotypes were assessed in 208 Tunisian subjects (78 males/130 females) by polymerase chain reaction-restriction fragment length polymorphism and allele-specific-PCR methods. Results Genotyping of ITPA revealed frequencies of 6% and 7.9% for c.94C>A and IVS2+21A>C, respectively. Accordingly, deficient or diminished ITPA phenotype can be predicted to concern 2.4% of Tunisians. The observed frequencies of the c. 238G>C, c.460G>A and c.719A>G TPMT polymorphisms were 0, 0.24 and 1.44%, respectively. Conclusion This study provides the first analysis of TPMT and ITPA mutant allele frequency in individuals of Tunisian origin. Unlike in Caucasians, TPMT*3C which harbours the c.719A>G polymorphism appears to be the most common mutant allele in Tunisians. In contrast, ITPA mutant allele frequency distribution appears to be similar to that observed in Caucasians.