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The research project included the following tasks:
1. Estimation of polyamine content in human milk, powder milks for babies and animals
2. Study of the effect of polyamine ingestion on the pancreas and liver postnatal maturation.
3. Analysis of the effect of putrescine ingestion on the postnatal maturation of the intestine.
4. Estimation of the intestinal permeability towards macromolecules in adult- and suckling rats treated with or without spermine.
5. Analysis of the effect of milk polyamine content on the intestinal permeability towards proteins in premature infants.
6. Ontogenesis of the mucous immune system in suckling rats treated with or without spermine.
7. Effects of food pollutants ingestion by nursing rats on parameters characterising the intestine and the liver of their pups.
8. Analysis of the spermine action mechanism.
9. Epidemiological study.
10. Therapeutic action of oral polyamines towards intensities of reactions presented by food allergic patients.
Tasks 9 and 10 were added during the project realisation.
The main results and conclusions are as follows.
Putrescine ingestion did not modify the maturation degree of the intestine in suckling rats. On the contrary, the oral administration of spermine or spermidine induced this phenomenon in the same animals. This observation was confirmed by two independent laboratories. For examples, we showed that oral administered spermine controlled the intestinal permeability towards macromolecules in suckling rats. This observation was also made by an independent laboratory The ingestion of spermine induced liver and pancreas maturation in unweaned rats. It modulated immunological properties in the same animals. These observations support the hypothesis that exogenous spermine could play a preventive role towards food allergy.
This last possibility is currently under investigation.
The polyamine concentration of human milk was measured from 60 women during a period extending from the 1st week to the 6th month of lactation. The polyamine content of 18 infant formulas was estimated. The spermine and spermidine content of these powdered milks was lower that that of the human milk. This observation was confirmed by four foreign laboratories. It has led to the proposal that the possible protective effect of human milk against allergies, which has been reported in the literature, could be partly explained by its high level of polyamines, especially spermine.
Preliminary results indicate that the intestinal permeability to macromolecules could be different in premature babies depending on whether they receive maternal milk, powdered milk without addition of spermine or powdered milk supplemented with spermine.
An epidemiological study was undertaken on a small scale. Consequently, the obtained results do not allow to formulate definitive conclusions. They showed a tendency (not significant) indicating that breast fed children (having drunk a milk rich in polyamines) are less often allergic than the others.
Spermine modified the proliferation and differentiation of T lymphocytes isolated from child tonsils and cultured in media containing phytohemagglutinin L.
Otherwise, in the suckling rat, the analysis of the action mechanism of oral administered spermine was deeply analysed at the level of the liver, the intestine and the pancreas. This polyamine acts either directly on the enterocytes or indirectly on the latter or pancreas- and liver cells (activation of ACTH, corticosterone, bombesin and cytokine secretion). In our experimental conditions, spermine did not induce carcinogenous lesions.
In order to study the therapeutic action of polyamine ingestion towards the allergic reaction intensity of patients suffering of food allergy, we measured the intestinal permeability to macromolecules in children with different intestinal diseases. Gastro-resistant pellets containing human a-lactalbumin were prepared. Preliminary results prove that our technique allows to confirm the presence of food allergy in children and to follow up the treatment chosen.
All these observations and other not cited above indicate that it is highly probable that exogenous spermine and spermidine are molecules able to prevent food allergy. Nevertheless, additional research needs to be undertaken in one coherent approach with sufficient critical mass to arrive at some definite answers (as, for example, to the rationale of adding polyamines to infant formulas, both as trophic factors and as prophylaxis against food allergy). Without such an approach, these research questions will most likely also be addressed but in a dispersed way.
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