Chlorophyll (Chl) and bacteriochlorophyll (Bchl) have been made water soluble by transesterfication with serine (Ser) at the propionyl residue and tested as potential reagents for photodynamic therapy (PDT). Photocytotoxicity of the conjugates Chl-Ser and Bchl-Ser in M2R mouse melanoma was tested in cell cultures. Tissue uptake and clearance of the photosensitizers in CDI nude and C57Bl mice implanted with M2R tumors are described, Photocytotoxicity in cell cultures was determined microscopically and by [3Hlthymidine incorporation. The LD.u values in vitro were 0.05-0

Background: Doping with erythropoietic proteins such as recombinant human erythropoietin (rHuEPO) and darbepoetin alfa is a serious issue in sport. There is little information on the time course of detection of rHuEPO in urine and on methods to evaluate electrophoresisbased data. Methods: We used a recently described isoelectric focusing method for detecting rHuEPO and endogenous EPO in urine obtained from individuals treated with placebo or epoetin alfa. The latter was administered subcutaneously at 50 IU/kg on days 0, 2, 4, 7, 9, 11, 14, 16, and 18. Blood and urine samples were collected during the morning of study days ؊3, 0, 2, 4, 7, 9, 11, 14, 16, and 18 and on days 2, 3, 4, and 7 postadministration. We developed visual and numerical (two-band ratio) techniques to evaluate the electropherograms for the presence of rHuEPO. Results: Compared with the placebo group, the epoetin alfa-treated group responded with increases in hematocrit, reticulocytes, macrocytes, serum EPO, and serum soluble transferrin receptor. The electropherograms showed that the pattern of bands arising from urinary rHuEPO is different from that of endogenous urinary EPO. Both the two-band ratio and the visual technique detected rHuEPO in all 14 epoetin alfa-treated individuals 3 days after the last dose. On the 7th day after the last dose, both techniques detected rHuEPO in approximately one-half of the participants. rHuEPO was not detected in the placebo-treated individuals. Conclusions: The isoelectric focusing method detects rHuEPO in most urine samples collected 3 days after nine doses of epoetin alfa. The numerical two-band

Two amphiphilic derivatives of chlorophyll, which have high potential as photodynamic therapy sensitizers for malignant melanoma have been investigated by a combination of laser flash photolysis and pulse radiolysis. It is shown that direct excitation of monomeric forms of these molecules in both hydrophilic and hydrophobic environments produces significant yields of the corresponding triplet states, which have been characterized in terms of spectral and kinetic parameters. In both environments, scavenging of the triplets by oxygen produces singlet oxygen, O2(1 delta g), with essentially unit efficiency as evidenced by time-resolved IR luminescence measurements.

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