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- W2740950963 abstract "In the fields of neuroendocrinology and behavioral pharmacology antisense technology has been successfully applied in numerous in vivo studies (for review see Wahlestedt, 1994; Landgraf, 1996). The down-regulation of the synthesis of proteins such as enzymes, neurotransmitters and neuropeptides and their receptors due to central administration of oligodeoxynucleotides (ODNs) can evoke specific neuroendocrine and behavioral effects in laboratory animals. However, in addition to sequence-specific effects of antisense ODNs that result from a highly specific complementary antisense binding to the targeted mRNA sequence, several other so called ODN binding mechanisms have been described, such as binding to membrane receptors (Yakubov et al., 1989; Akhtar and Juliano, 1992; Stein et aI., 1993; Figure 1). Moreover peripherally or centrally administered ODNs produce in a dose-dependent manner several non-specific and sometimes toxic effects which are sequence-independent. Thus potentially toxic side effects, including decreased blood clotting and cardiovascular problems such as increased blood pressure and decreased heart rate, have been observed in animal studies that have served for the basis of early human trials (Gura, 1995). Furthermore, intraperitoneal administration of phosphorothioate ODNs to mice was associated with toxic hematological and histopathological effects (Sarmiento et aI., 1994). Galbraith et al. (1994) also reported transient hemodynamic changes and complement activation following systemic infusion of phosphorothioate ODNs in monkeys. Moreover, a potent activation of lymphocytes and the production of antiDNA-antibodies has been described (Krieg, 1995). Perez and coworkers (1994) observed sequence-independent effects of ODNs in vitro in cultured primary cells and cell lines as well as in vivo in mice. In diverse cell types different ODNs, including sense molecules, independent of their base sequence, mediated the induction of an Sp 1 nuclear transcription factor. The induction of Spl activity was also seen in spleen cells one day after the subcutaneous injection of ODNs to mice." @default.
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- W2740950963 date "1998-01-01" @default.
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- W2740950963 title "NON-SPECIFIC EFFECTS OF CENTRALL V ADMINISTERED OLIGONUCLEOTIDES" @default.
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