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Date: 27 Jun 2005
Time: 21:29:24
Remote Name: 67.53.49.252
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From: Vladimir V. Ryl'kov ryl@ilph.spb.su
Date: 8/24/99
Time: 2:20:51 AM
Remote Name: 194.85.123.97
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Dear Dr. Karu: You are perfectly right, marking, that concentration of PD drug is rather high from pharmacological point of view and may cause PD effects (your first argument). However, from an optical point of view this concentration is too small and can't influence the quantity of light captured by endogenic absorbers. Therefore, the rate of light absorption by endogenic absorbers would be essentially the same in both cases (with and without PD drug), and the efficiency of primary photoreactions wouldn't be impaired. Should one agrees with your second argument, that the concentration of endogenic chromophores absorbing light in red and near IR areas is too low and that only very weak photoreactions resulting in insignificant immunomodulation can be expected, then the phototherapy in general and the low-power laser therapy in particular would be impossible. We have observed a photostimulation of tumor growth in mice not treated with PD drug (and in some cases in PD-treated ones) by use of red light of the laser at light intensities and dozes typical for PDT treatment (Reference 1 of our paper). Therefore, the endogenic absorbers despite the rather low concentration can mediate an effective photostimulation of biochemical processes in a living organism (body). Yes, the effects of PD drugs on mitochondria mentioned in your letter (your third argument) should be taken into account and. However, it should be emphasized that the PD drugs used by us were the drugs adopted for use by pharmacological regulating documents, and that the doses and schedule of their administration to mice corresponded to those recommended for clinical use. During our experiments, these drugs showed no dangerous side effects similar to those characteristic of wide-known mitochondrial poisons like di- or trinitrophenol affecting oxidative phosphorilation. The influence of a PD drug on mitochondria is not a unique point of PD interaction with components of tissues and cells, and the photoreactions of the respiratory chain carriers are not a unique photoresponse of organism. For the purpose of immunomodulation, the photoresponses, associated with receptors of cell membranes, may be even more important than the photoresponses generated inside the cell. Nevertheless, as to the situation with mitochondria discussed by you, a damage of the respiratory chain carriers photosensitized by a PD drug should be considered only as a competitive photoreaction (competing with the photoreactions of the carriers), doubtfully affecting the efficacy of the latter ones. Certainly, if one evaluates the efficiency of photoreactions by a remote biological effect rather than by a quantum yield of primary photoproducts, then the estimate may be influenced by cooperative effects of various photoreactions coming from different compartments of the cell. These usual kinetic effects do not conflict with our statement but certainly should be taken into account considering their strong dependence on the conditions of the PDT treatment. In order that the efficiency of primary photoreactions of respiratory chain carriers to be affected, an incredible assumption should be made that the administration of a PD drug would change optical and photochemical properties of the whole stock of respiratory chain carriers.
Sorry for belated answer. We were absent.
Sincerely yours, Vladimir V. Ryl'kov.