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After intravenous injection of a low dose (25 mug/kg) in rats, the anti HIV-1 compound succinylated human serum albumin (Suc-HSA) is taken up mainly in the liver and spleen and is proteolytically degraded. Ten minutes after injection of I-125-Suc-HSA, 72 and 14% of the dose were found in the liver and spleen, respectively. With immunohistochemistry we demonstrated that in both organs, Suc-HSA was specifically endocytosed in endothelial cells. In the isolated perfused rat liver preparation, liver uptake was shown to be saturable, with a K(m) of 2.9 10(-8) M and a V(max) of 2.4 mug/min/100 g body weight. The apparent K(m) and V(max) in vivo were 2.2 10(-7) M and 10.3 mug/min/100 g, respectively. Uptake in liver and spleen was inhibited by preadministration of an excess of formaldehyde-treated albumin and with polyinosinic acid, indicating the involvement of the scavenger receptor, as anticipated for such polyanionic compounds. Suc-HSA is not absorbed intact from the colon and the ileum. After injecting (i.v.) rats with a high dose of Suc-HSA (10 mg/kg), the elimination t1/2 was 3 hr, and therefore, sustained plasma levels above the concentration needed for in vitro anti-HIV-1 activity can be achieved.

This chapter highlights the most significant applications of pyrroles, indoles, carbazoles, and related heterocycles for the period 1995–June 2006. Sections on polymers and dyes deal mainly with applications of these heterocycles in the preparation of conducting polymers, mechanical actuators, drug delivery systems, organic devices, and sensors. The survey of natural products covers substances from bacteria, fungi, plants, and marine organisms, and has been restricted to new structures with brief mention of properties or bioactivity where appropriate. Both old and new compounds that are under investigation as medicinal compounds, including antibacterials, antitumor, anti-HIV, antiviral, and anti-inflammatory agents, are presented. Only new compounds that have been approved as drugs or have been considered as agrochemicals are listed in the relevant sections. Finally, a section has been included that centres on calixpyrroles as selective sensors for anions

This chapter highlights the most significant applications of pyrroles, indoles, carbazoles, and related heterocycles for the period 1995–June 2006. Sections on polymers and dyes deal mainly with applications of these heterocycles in the preparation of conducting polymers, mechanical actuators, drug delivery systems, organic devices, and sensors. The survey of natural products covers substances from bacteria, fungi, plants, and marine organisms, and has been restricted to new structures with brief mention of properties or bioactivity where appropriate. Both old and new compounds that are under investigation as medicinal compounds, including antibacterials, antitumor, anti-HIV, antiviral, and anti-inflammatory agents, are presented. Only new compounds that have been approved as drugs or have been considered as agrochemicals are listed in the relevant sections. Finally, a section has been included that centres on calixpyrroles as selective sensors for anions

After intravenous injection of a low dose (25 mug/kg) in rats, the anti HIV-1 compound succinylated human serum albumin (Suc-HSA) is taken up mainly in the liver and spleen and is proteolytically degraded. Ten minutes after injection of I-125-Suc-HSA, 72 and 14% of the dose were found in the liver and spleen, respectively. With immunohistochemistry we demonstrated that in both organs, Suc-HSA was specifically endocytosed in endothelial cells. In the isolated perfused rat liver preparation, liver uptake was shown to be saturable, with a K(m) of 2.9 10(-8) M and a V(max) of 2.4 mug/min/100 g body weight. The apparent K(m) and V(max) in vivo were 2.2 10(-7) M and 10.3 mug/min/100 g, respectively. Uptake in liver and spleen was inhibited by preadministration of an excess of formaldehyde-treated albumin and with polyinosinic acid, indicating the involvement of the scavenger receptor, as anticipated for such polyanionic compounds. Suc-HSA is not absorbed intact from the colon and the ileum. After injecting (i.v.) rats with a high dose of Suc-HSA (10 mg/kg), the elimination t1/2 was 3 hr, and therefore, sustained plasma levels above the concentration needed for in vitro anti-HIV-1 activity can be achieved.