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Peptidic toxins extracted from spider, marine snails or snakes venoms, have considerably helped the pharmacological characterization of calcium channels. They have successfully been used for calcium channels mapping. However, the actual situation remains unclear. Genetic investigations demonstrated the existence of a great number of types or sub-types of calcium channels. In recent year a large number of toxins have been purified. Many of these toxins have specific actions on calcium channels and have been used as powerful tools in pharmacological approaches of calcium channels. However the pharmacology of the calcium channels remains very limited, many of them are waiting for the discovery of pharmacological tools allowing their molecular approach in order to determinate their biological implications. In this paper we describe the different families of calcium channels and toxins that interact with these channels. We also recapitulate the "non defined" calcium channels i.e. calcium channel which does not correspond to a N, L, P/Q, R or T type channel and for which no effector are available. We report the discovery and characterization of mapacalcine, a toxin extracted for a marine sponge, as an example of an approach of an undefined calcium channels first characterized by electrophysiological techniques and for which a specific toxin has been purified allowing its pharmacological approach. We also state the possible role of calcium channel toxins in the domain of therapeutic applications.

Calcium channel blockers are also termed calcium antagonists or calcium entry blockers. The use of calcium antagonists for the management of hypertension is well established. Their control of vascular tone is related to their interaction with the alpha 1 subunit of L-type calcium channels. This interaction is not simple since prolonged depolarisation promotes the inactivated state of the channels resulting in a change of affinity which is different for various molecules so far considered. The isoforms of alpha 1 subunits and the duration of the stimulus required to activate heart or vessels are important parameters to be considered with the nature of the molecule. Those parameters influence the vascular selectivity which is quantified as the ratio of the concentrations required to reduce by 50% the contraction of heart and of vessels. This selectivity is an important component in the therapeutic action. Another component of this action is the prevention of structural changes noted in heart and arteries. As well as lowering blood pressure, calcium channel blockers have also been found to exert blood pressure independent effects. For instance, they reduce cardiac and vascular hypertrophy and avoid renal damage. In the stroke-prone rat, such protective effects are accompanied by reduction of the salt-dependent overexpression of the gene of endothelin-1 and of fetal genes associated with cardiac hypertrophy. This paper summarizes available information about those components and discuss their significance.

This paper reviews the present state of the studies on the repair of a major oxydative lesion on DNA, the 8-oxo-guanine (8-OxoG). This modified base has been proved to be highly mutagenic and therefore implicated in the ethiology of several pathologies. The cloning of the yeast OGG1 gene, a functional homolog of the fpg from bacteria, allowed the isolation of the mammalian homologs. These genes code for 8-OxoG DNA glycosylases/lyases, whose biochemical properties are consistent with their postulated role as the main defence against the genetic instability induced by the presence of 8-OxoG in DNA. This, together with the mutator phenotype of the yeast ogg1 mutant strains, make of the human OGG1 a candidate for a cancer predisposition gene. The localization of this gene to chromosome 3p and other evidences discussed in this paper indicate that OGG1 could be a tumor suppressor gene implicated in lung cancer.

Commitment and differentiation of hematopoietic stem cells are associated with the progressive restriction of cellular proliferation and the progressive expression of a subset of genes encoding the markers of mature cells. These two processes are genetically regulated and, in this paper, I review the expression and function of the GATA family of transcription factors as an example of this genetic regulation. GATA cis-acting elements are found in most of the regulatory regions of T-lymphoid, erythrocytic and megakaryocytic restricted genes. These GATA motifs are recognized by the members of a family of transcriptional regulators: the GATA family. Three members of this family, GATA-1, 2 and 3 are expressed in hematopoietic cells. They are necessary for the erythrocytic and megakaryocytic lineages (GATA-1), for the T-lymphoid lineage (GATA-3), and for the proliferation of uncommitted hematopoietic precursors (GATA-2). GATA-1 displays at least four functions: activation of the erythrocytic and megakaryocytic specific genes, regulation of the epsilon-->gamma globin switch and control of the cell cycle. These two last functions will be discussed to show the multiple facets of GATA-1 in the genetic regulation of hematopoiesis.

The aim of this paper is to indicate the main strengths which are involved in the spread of insecticide resistance genes. These forces are more or less well known in population genetics, there are: mutations which are involved in the creation of new alleles well adapted to insecticides; migration which is responsible for the geographical extension of resistance and selection which screened among the various alleles those which are best adapted in the geographical and ecological context. The biological model described in this paper is the mosquito Culex pipiens which is the best known model at that time. Many works have been done on the resistance to insecticides in this species. On the other hand, the molecular mechanisms involved in insecticide resistance have been described from various invertebrates.