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Project List » METHYLATION METABOLISM EVALUATION BY COMPETITIVE REACTIONS WITH METHYL-DONOR RADICALS, METHYLATION PROCESSES METABOLITES EXPRESSIVITY’S IN NEUROENDOCRINOLOGICAL PATHOLOGY. PREVENT MEASUREMENTS AND METHODS.

METHYLATION METABOLISM EVALUATION BY COMPETITIVE REACTIONS WITH METHYL-DONOR RADICALS, METHYLATION PROCESSES METABOLITES EXPRESSIVITY’S IN NEUROENDOCRINOLOGICAL PATHOLOGY. PREVENT MEASUREMENTS AND METHODS.
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Acronym: RADIMET
Number / Date of the contract: CEEX 91/2006 / 01.09.2006
modul 1
Project Manager: Diana Chiper
Partners:
Starting date / finishing date: 2006-09-01 / 2008-10-01
Project value: 1500000 RON
Abstract: RADIMET project will develop new complex researches (with fundamental and applicative research character) regarding the methylation mechanisms and their expressivities, and the involvement degree in different pathologies, defining some specific markers, based on the investigation of some fundamental processes of biochemical and molecular order – endogenous methylation processes. The project is conceived modularly, involving: A. Preclinic module, on animals, approaching different techniques for the study of the kinetics evaluation of the concurrent processes of methylation (determinations of equilibrium constants, kinetics), with the evaluation of the level of metabolites resulted from processes of metabolic methylation and the observation of specific markers, report evaluation between the methyl radical donor biovector and toxic metabolite (homocisteine) which will be determined by quantitative reports between the methyl radical and homocistein at the equilibrium moment, and the report between homocisteine and DNA hypermethylated (report value being of high expresivity pathology evaluation) (original elements of the project). The obtained results expected to be are of major importance in the determination of the causes and the definition of the role and the involvement of methylation processes in neuroendocrine pathology. The researches during this project gives the possibility to the working team to integrate into the prioritary objectives regarding the health, foreseen in the international projects from the EU programme, FP 7. The methods and techniques used are highly performing and sensitive, using methyl radical donor biovectors, the methyl radical being marked with 14C, or with T, observable by measurements of radioactivity during the experimentations. B. The clinic module, involved age pathology, regarding the non-equilibrium of endocrine and psycho-affective non-equilibrium, and cardiovascular and cerebrovascular pathologic states. The methods and techniques used are non-invasive. The final target is to standardise some methods that allow the evaluation of the reports concentration methyl-radical/homocisteine, methyl-radical/Folates homocisteine/DNA hypermethylated, of risk specific to the pathology approached with final impact in improving the prevention and treatment and monitoring schemes (individualised medicine) health state at national level. Romanian research did not contain yet a clear message regarding the attempt of trans-methylation mechanisms and metabolites. Also, the national epidemiological studies did not include attempts and methods related to merthylation disturbances in the pathology putted under study in our Project. Implicitly, there is not a database regarding the evaluation of the risk values of Methyl-group/Homocysteine, and Methyl-group /Folates ratios specific for a given pathology. However, the interest for the systematic attempts in this field are just present, and some research teams actually try to include studies regarding the correlation between the methylation degree and early detection and treatment of cancer. Even if the effect of different methyl-group donors (S-Adenosylilmethionine, Choline or Trimethyl-glycine, etc) or that of some substances modulating the methylation processes in different pathological states is widely investigated worldwide, we did not found in the literature studies regarding the competitive behavior of methyl-group donors and its therapeutic impact. This constitutes the original attempt of our Project, which aims to elucidate the metabolic pathways of each of the donors, as well as the features of their competitive metabolism, in order to emphasize the causality of the pathology under study. The standard methods and the markers we envisage to elaborate based on the obtained results could further be transferred in some clinical units, contributing to the improvement of the diagnostic methods and of the therapeutic arsenal, and consecutively, to the improvement of the prophylactic and curative actions at the national level. The present project is multidisciplinary research that couples the biomolecular researches and for the elaboration of early methods of diagnosis and therapeutic performing algorithms, in the context the actual wishes of the individualized medicine.

THE STAGES OF THE PROJECT AND DELIVERY DATES
1. Disorders of the methylation processes; induced pathology; selection of the investigation and diagnosis methods; preliminary work for the preparation of the experiments. Informational database; Acquisition. (2006-12-01)
2. Stage II – Study of methylation process under the influence of SAM as methyl-group donor, on the normal subjects. Study regarding the methylation process under the influence of Choline as methyl-group donor, on the normal subjects. Study of the methylation process by competition mechanism between Choline and SAM on the normal subjects. (2007-05-31)
3. Study regarding the methylation process under the influence of SAM as methyl-donor, with different pathologies. Study of the methylation process under the influence of administered Choline as methyl-donor on the subjects with different pathologies Study of the methylation process by competition mechanism between Choline and SAM on the subjects with different pathologies. (2007-12-01)
4. Data processing; Homocysteine level investigation protocol in healthy human subjects and the selected patients. National Propose for health-state monitoring of people through evaluation HOMOCYSTEINE as a new parameters. (2008-12-01)

RESULTS


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