摘要:

Abstract:Short lived reaction intermediates such as triplet stam and free radicals can be detectedin vivousing laser photolysis techniques with time‐resolved diffuse reflectance detection. This novel approach is illustrated for bacterial suspensions ofBacillus subtili

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1992.tb02183.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract—Exposure of lambda phage to 658 nm light in the presence of 5,10,15,20‐tetrakis‐(1‐methyl‐4‐pyridyl)‐21H,23H‐prphine, tetra‐p‐tosylate leads to complete (<7 logs) inactivation as measured by the plaque assay. The sensitizer without light and 658 nm photolysis of lambda phage in the absence of sensitizer do not lead to a measurable decrease in viral inactivity. Viral inactivation is not dependent upon the

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1992.tb02184.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract—The photocycloaddition reaction between a 4′,5′‐dihydropsoralen derivative and thymine was studied in solution using a synthetic bichromophoric model 8 in which the two rings are associated by a tetramethylene chain. In water this model molecule exhibits intramolecular ring‐ring stacking interactions as evidenced by UV and NMR spectroscopies. Irradiation at 365 nm at usual concentrations ( 5.10−‐4M) leads exclusively to a regio‐ and stereo‐selective dimerization reaction involving the 3,4 double bonds of the psoralen moities. Extreme dilutions (ca2.10−‐5M) were necessary to observe the intramolecular reaction which results in the exclusive formation of a 3,4cb‐antiadduct. This reaction is completely reversed by irradiation at 254 nm. These results are discussed with regard to the behavior of the homologous models in which the furan part of the psoralen ring is not hydrogenated, These latter compounds also lead exclusively to a 3,4cis‐antiadduct. It appears that saturation of the furan ring increases strongly the quantum yield of the photaddition at 365 nm (0.01 → 0.18) and that the triplet excited state of the 4′,5′‐dihydropsoralen

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1992.tb02185.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract—Singlet‐oxygen (1O2) was generated in the gas phase by heterogeneous photosensitization and bubbled into suspensions of phosphatidylcholine (PC) liposomes. Lipid peroxidation and membrane lysis were observed, and were dependent on the1O2concentration and the degree of unsaturation of the liposome. An analysis based on large target diffusion theory indicates that approximately 5000, 2800, and 1600 interactions were required for the lysis of large dioleoylPC, dilinoleoylPC and dilinolenoylPC liposomes, respectiv

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1992.tb02186.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract—Using 1‐anilino,8‐naphthalenesulfonic acid (ANS) as a probe, we examined properties of micelles of Cremophor EL, an amphipathic agent which can solubilize hydrophobic photosensitizing agents and promote their distribution to plasma lipoprotein. In aqueous solution, Cremophor micelles persisted for several hours after dilution below the critical micellar concentration (CMC). After equilibrium was reached, we found a CMC of 0.009% (wt/vol). Fluorescence data suggest that the micellar environment of ANS binding has a dielectric constant of approximately 27. Cremophor also reverses examples of multi‐drug resistance associated with impaired accumulation of anti‐tumor agents,e.g. daunorubicin. Although the latter drug is relatively hydrophilic, fluorescence spectroscopy and anisotropy studies indicate an association with Cremophor. Moreover, resistance reversal occurred only at Cremophor concentrations abov

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1992.tb02187.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract—Hypocrellin A (HA), a peryloquinone derivative, has recently been isolated from a fungusHypocrella bambusae. This lipid soluble pigment, in combination with phototherapy, has been used to treat many skin diseases including the keloids caused by scalding and burns. We have studied the effects of photosensitized HA on biomembranes using pig heart microsomes. Photosensitization of HA was found to peroxidize the membrane lipids in the cardiac microsomes. The photodamage imposed by HA depended not only on the concentration of HA but also on the time of irradiation and pH of the system. Superoxide dismutase (SOD), ascorbic acid, β‐carotene and 5,5‐dimethyl‐1‐pyrroline‐N‐oxide (DMPO) inhibited the lipid peroxidation ˜50, ˜50, ˜30 and ˜97%. respectively. Spin trapping in combination with EPR spectroscopic techniques was used to identify the reactive free radicals during the photoreaction. Formation of superoxide anion radical, (O2), was identified by the SOD‐inhibitable DMPO‐O2‐‐EPR spectrum. Both SOD and ascorbic acid inhibited the EPR signal intensity in a dose‐dependent manner with rate constants of 6.78 × 108M−1s−11.82 × 104M−1S−1respectively. The lifetime of O2, under these conditions, was found to be 1.1 s. Photoirradiation of HA yielded a HA free radical with ag= 2.002 which was not suppressed by SOD but in the presence of reductants such as ascorbic acid and catechol the spectrum was completely suppressed. The increase of the EPR signal intensity and malondialdehyde formation with increasing pH may be due, in part, to the production of predominant *HA−species at high pH which would be more reactive with oxygen to yield O2. These results indicate that the lipid peroxidation of the cardiac membranes observed during photooxidation of HA may arise, in part, from the interaction of membrane lipids with reactive species of oxygen and HA free radi

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1992.tb02188.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract—The relative importance of type I and type II mechanisms in the photodynamic treatment of red blood cell concentrates (RBCC) to inactivate viruses was studied using aluminum phthalocyanine tetrasulfonate (AlPcS4), visible light and quenching or enhancing agents of reactive forms of oxygen. Treatment of a human RBCC with 10–13 μM AlPcS4and 25–26 rnW/cm2visible light resulted in the rapid and complete inactivation of added vesicular stomatitis virus (VSV). The addition of mannitol, glycerol, reduced glutathione (GSH), or superoxide dismutase (SOD), known quenching agents of type I mechanisms, had little to no effect on the rate of inactivation of VSV. Significant inhibition of VSV kill was observed on addition of tryptophan or sodium aide, known quenchers of type II mechanisms. Additionally, the rate of VSV kill was enhanced in the presence of D2O. Taken together, these results indicate a predominant role of singlet oxygen in the inactivation of VSV on photodynamic treatment of RBCC.The relative importance of type I and type II mechanisms on cellular toxicity was also evaluated. Little, if any hemoglobin release was observed on treatment of human or rabbit RBCC with 10 μMAlPcS, and 44 J/cm2of visible light in the presence or absence of the above mentioned quenchers. The effect of the addition of quenchers on the recovery and circulatory survival of treated, autologous rabbit RBCC, labeled with51Cr, was also assessed. As compared to a circulatory half‐life (T50) of 10–12 days for the untreated controls, RBCC treated with 30 min light exposure and 5 or 10 μMAlPcS, or 5 μMAlPc had T50values of 5 days or less. The addition of 1 mM GSH, 1 mM mannitol, or 1 mM tryptophan prior to treatment with 30 min light exposure and 10 μMAlPcS, resulted in T50values of 7.9–8.5, 6.5 and 8.5 days, respectively. A similar T50enhancement was observed on addition of 0.5 mMtryptophan to RBCC prior to treatment with 10 μMAlPc and 30 min light. We conclude that virus kill in the RBCC operates principally through a type II mechanism, whereas both type I and type II mechanisms contribute to red cell cytotoxicity, as measured by circulatory survival in a rabbit model. Consequently, the specificity of virus kill on treatment of a RBCC by photodynamic processes can be enhanced through the addition of quenchers of

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1992.tb02189.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract—Isolated rat liver mitochondria have been used to study the mechanism of toxicity of Rhodamine 123 (Rho 123) in the dark and after irradiation with visible light. We report an inhibition of adenosine 5′‐diphosphate phosphorylation which is increased after illumination. In the dark, the first steps of the phosphorylation process (i.e. the entry of substrates into the matrix, the electron transport to oxygen and the creation of the proton gradient) as well as ATPase activity are not significantly perturbed at Rho 123 concentration below 10 μg/mL. In contrast, the movements of the phosphate compounds are drastically impaired. Irradiation strengthens the detrimental effects in an oxygen dependent process. The nature of the noxious transient species is not clearly established, but it is suggested that singlet oxygen could be responsible for the observed

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1992.tb02190.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract—The photoactivated antiviral and cytotoxic activities of the naturally occurring thiophene, α‐terthienyl (1), and 15 synthetic analogues were evaluated against murine cytomegalovirus and Sindbis virus, and murine mastocytoma cells. After irradiation with near UV light, α‐terthienyl and most of its analogues had significant toxicity, with minimum inhibitory concentrations in the range of 0.02–40 μM. In the absence of near UV irradiation, only one analogue had antiviral activity and five were cytotoxic. The most active analogues were those containing carboxylic acid, hydroxyl, or cyano substituents. Quantitative structure‐activity relationship analysis of thiophene phototoxicity suggested that the rate of singlet oxygen production is the primary determinant of antiviral and cytotoxic activities. For phototoxicity against murine cytomegalovirus, a significant role for hydrophobicity was also demonstrated. Tricyclic thiophenes show significant potential for photochemotherapy of viral infections and cancer. and further evaluation in animal models is

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1992.tb02191.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY

摘要:

Abstract—The differential sensitivity to merocyanine 540 (MC540)‐sensitized photoirradiation of leukemia cells, selected solid tumor cells, and normal pluripotent hematopoietic stem cells has been successfully exploited for the extracorporeal purging of simulated autologous remission bone marrow grafts. In this communication, we compare the effects of fractionatedvscontinuous irradiation upon the MC540‐sensitized photoinactivation of L1210 and K562 leukemia cells. Exposure to MC540 (15 μg/mL) and fractionated doses of white light inactivated fewerin vitroclonogenic cells than exposure to an equivalent dose of continuous irradiation, provided the irradiation doses were small (8.1–16.2 kJ/m2) and spaced 1–2 h apart. The dye‐sensitized photoinactivation of leukemia cells was enhanced when cells were stored at 4°C instead of 37°C between irradiation periods, most likely in part because the cells were unable to repair sublethal photodynamic damages at the lower temperature. These data suggest that cells can recover from sublethal damage inflicted by the plasma membrane‐active photos

ISSN:0031-8655    

DOI:10.1111/j.1751-1097.1992.tb02192.x

出版商:Blackwell Publishing Ltd    

年代:1992

数据来源: WILEY