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E Ben-Hur

Publications and source records attributed to E Ben-Hur.

At least 37 records · Page 2Linked to original sources
PubMed1996

Inactivation of Trypanosoma cruzi trypomastigote forms in blood components with a Psoralen and Ultraviolet A light.

Inactivation of the blood-borne parasite Trypanosoma cruzi by UVA and 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT) was studied in the blood components fresh frozen plasma (FFP) and platelet concentrate (PC). The AMT was utilized at a concentration of 50 micrograms/mL and the inactivation procedure included the flavonoid rutin (at 0.35 mM), a quencher of type I and type photo-reactants, which we have previously found to maintain platelet integrity during this treatment regimen. Within both FFP and PC, complete inactivation of the infective form of T. cruzi, the trypomastigote, was achieved at a UVA (320-400 nm radiation) fluence of 4.2 J/cm2. We note that while the infectivity of the parasite is eliminated at 4.2 J/cm2 the trypomastigote motility continues for at least 16 h-post-treatment and is inhibited only after much higher light doses. Isolation of total DNA from the parasite cells after treatment in the presence of 3H-AMT indicated that at the lethal UVA influence about 0.5 AMT adducts per kilobase pairs occurred. These results suggest that this psoralen plus UVA methodology which shows promise in enhancing the viral safety of PC, may in addition eliminate bloodborne T. cruzi, the causative agent of Chagas disease.

Animals↗
PubMed1995

Virucidal short wavelength ultraviolet light treatment of plasma and factor VIII concentrate: protection of proteins by antioxidants.

The use of solvent/detergent mixtures and various forms of heat treatment to inactivate viruses has become widespread in the preparation of blood derivatives. Because viruses that lack lipid envelopes and/or are heat resistant, eg, hepatitis A virus (HAV) or parvovirus B19 may be present, the use of two methods of virus elimination that operate by different mechanisms has been advocated. We now report on short wavelength ultraviolet light (UVC) irradiation for virus inactivation and enhancement of its compatibility with proteins by quenchers of reactive oxygen species (ROS). Treatment of an antihemophilic factor (AHF) concentrate or whole plasma with 0.1 J/cm2 inactivated 10(5) to > or = 10(6) infectious doses (ID) of encephalomyocarditis virus (EMCV), HAV, bacteriophage M13, vesicular stomatitis virus (VSV), and porcine parvovirus. However, the recovery of factor VIII was 30% or lower on treatment of an AHF concentrate and 60% on treatment of plasma. Factor VIII recovery could be increased with little or no effect on virus kill by addition of rutin, a flavonoid known to quench both type I and type II ROS. On treatment of plasma in the presence of rutin, the recovery of several other coagulation factors was also enhanced by rutin addition and typically exceeded 75%. Electrophoretic analysis of treated AHF concentrate confirmed the advantage of rutin presence; UVC irradiation of plasma did not cause discernible changes in electrophoretic banding patterns, even in the absence of rutin. We conclude that addition of UVC treatment to existing processes used in the manufacture of blood derivatives will provide an added margin of safety, especially for nonenveloped or heat-stable viruses.

Animals↗
PubMed1995

High-performance liquid chromatographic determination of the silicon phthalocyanine Pc 4 in human blood.

A sensitive and reproducible method has been developed for the measurement of the silicon phthalocyanine Pc 4 in red blood cell concentrates (RBCC). The procedure involves extraction of the RBCC with acetonitrile, purification of the extracts with reversed-phase Sep-Pak C18 cartridges and determination of Pc 4 in the extracts by high-performance liquid chromatography (HPLC) using a reversed-phase C18 column. The detection limit with 1-ml RBCC samples is 2 ng. This method is applicable to monitoring Pc 4 during its use as a photosensitizer for the inactivation of viruses in RBCC prior to transfusion. It has the potential to be adapted for measuring Pc 4 in tissues during its use in photodynamic therapy of cancer.

Chromatography, High Pressure Liquid↗
PubMed1995

Elimination of potential mutagenicity in platelet concentrates that are virally inactivated with psoralens and ultraviolet A light.

BACKGROUND: For virus sterilization of platelet concentrates (PCs), treatment with aminomethyltrimethyl psoralen (AMT) and long-wavelength ultraviolet A light (UVA) has shown efficacy. It has been found that treatment with 50 micrograms per mL of AMT and 38 J per cm2 of UVA in the presence of 0.35-mM rutin efficiently kills viruses while maintaining platelet integrity. There is, however, concern about the mutagenic potential of psoralens and UVA (PUVA)-treated PCs. STUDY DESIGN AND METHODS: Adsorption of PUVA-treated PCs with a hydrophobic resin containing C18 as the ligand was used for AMT removal, which was quantitated by the use of radioactive AMT. PUVA-treated PCs, with and without C18 treatment, were examined for solution pH and platelet aggregation response to agonists. In addition, residual AMT activity was determined by AMT's virucidal activity or incorporation into cellular DNA upon a second UVA irradiation and by its mutagenic potential in the Ames test. RESULTS: After PUVA treatment of PCs, residual AMT retained virucidal and adduct-forming ability upon re-exposure to UVA, but activities were less than those observed originally. As has been found previously, AMT had mutagenic potential following incubation in the dark with rat liver S9 microsomal enzymes. The PUVA treatment reduced this potential by 90 percent. C18 adsorption following PUVA treatment had no negative effect on platelet integrity and eliminated 50 percent of the added radioactive AMT. In addition, all detectable virucidal, nucleic acid-modifying, and mutagenic activities of AMT-treated PCs were removed by C18. CONCLUSION: These results suggest that hydrophobic resin adsorption of PUVA-treated PCs will conveniently remove functional psoralens and eliminates their mutagenic potential.

Adsorption↗
PubMed1995

Virus inactivation in red cell concentrates by photosensitization with phthalocyanines: protection of red cells but not of vesicular stomatitis virus with a water-soluble analogue of vitamin E.

BACKGROUND: Photodynamic treatment of red cells (RBCs) with phthalocyanines and red light inactivates lipid-enveloped viruses, such as vesicular stomatitis virus (VSV) and human immunodeficiency virus. To protect RBCs from photodynamic damage, type I free radical quenchers, such as mannitol, which did not affect virus inactivation, were added. STUDY DESIGN AND METHODS: Aluminum phthalocyanine tetrasulfonate (AIPcS4) was found to inactivate VSV at a rate one-fourth that of the silicon phthalocyanines (Pc 4 and Pc 5). However, the latter also caused more RBC damage. To protect RBCs against this photodynamic damage, Trolox, a water-soluble vitamin E analogue, was used. RBC damage was measured as potassium leakage or hemolysis during storage after treatment. In addition, reduction in negative surface charge on RBCs was measured immediately after treatment, and the effect of Trolox on VSV inactivation in RBCs was evaluated. RESULTS: Trolox at a concentration of 5 mM was found to reduce potassium leakage during storage after Pc 4 and AIPcS4 photodynamic treatment of RBCs. Hemolysis during storage of RBC concentrates treated with Pc 4 or Pc 5 was drastically reduced by the addition of 5 mM Trolox prior to light exposure. At the same concentration, Trolox inhibited the reduction of negative surface charges on RBCs following Pc 4 and Pc 5 photodynamic treatment. Under these conditions, VSV inactivation by photodynamic treatment with all phthalocyanines was not affected by Trolox. In aqueous solution, Trolox formed a complex with AIPcS4, thus quenching the excited triplet state of AIPcS4 at a constant rate of 8.8 x 10(6) per M per second. CONCLUSION: These findings indicate that Trolox protects RBCs from phthalocyanine-photosensitized damage without affecting virus kill. The addition of Trolox would be beneficial for improving the quality of RBCs subjected to photodynamic treatment.

Blood Transfusion↗
PubMed1995

Selective protection against IgG binding to red cells treated with phthalocyanines and red light for virus inactivation.

BACKGROUND: Irradiation with red light of red cells (RBCs) containing the photodynamically active phthalocyanine (Pc) dyes is being studied for inactivation of lipid-enveloped viruses. One of the outstanding problems with this treatment is the binding of IgG to RBCs. The effects of oxygen and type I or type II quenchers on this IgG uptake were evaluated. STUDY DESIGN AND METHODS: The Pc compounds used were aluminum phthalocyanine tetrasulfonate (AIPcS4), HOSiPcOSi(CH3)2(CH2)3N(CH3)2 (Pc 4); HOSiPcOSi(CH3)2(CH2)3N+(CH3)3I- (Pc 5); and SiPcOSi[(CH3)2(CH2)3N+(CH3)3](2)2I- (Pc 6). RBCs were analyzed by flow cytometry for the presence of IgG. RESULTS: Irradiation with red light for 30 minutes of RBCs containing either 2 microM Pc 4, 2 microM Pc 5, 2 microM Pc 6, or 6.5 microM AIPcS4 resulted in an uptake of IgG. These conditions completely inactivated the lipid-enveloped vesicular stomatitis virus (VSV) (> 5 log10 kill). IgG uptake was reduced when oxygen was depleted. The addition of reduced glutathione (GSH) or mercaptoethanol prevented the binding of IgG with RBCs treated with AIPcS4, Pc 4, Pc 5, and Pc 6. Specific binding of IgG2 but not of C3d was observed upon irradiation of RBCs with Pc 5 and Pc 6 in the absence of GSH. No gross changes were observed in RBC antigen strength after irradiation with the dyes in the presence of GSH. Inactivation of VSV by Pc plus light was not affected by GSH. CONCLUSION: Sulfhydryl compounds are useful in preventing IgG binding to RBCs following Pc photosensitization. Since virus inactivation proceeds at the same rate in the presence and the absence of sulfhydryl compounds, their addition to treated RBCs should allow crossmatching for transfusion after treatment. The binding of IgG depends to a large extent on the generation of reactive oxygen species.

Antiviral Agents↗
PubMed1995

Role of oxygen in the phototoxicity of phthalocyanines.

The presence of molecular oxygen is a determinant in the phototoxicity of phthalocyanines, and photosensitized oxidation is the accepted chemical mechanism for photo-dynamic action. However, it is difficult to establish whether the process is initiated by a type I electron transfer, or by a type II energy transfer reaction to form singlet oxygen. Usually, the involvement of singlet oxygen in photodamage has been indicated by the inhibition of the biological effect by a competitive physical or chemical singlet oxygen quencher, or by a rate increase in D2O, in which singlet oxygen has a longer lifetime than in H2O. Unfortunately, these techniques are not completely specific for singlet oxygen. Moreover, thermodynamic considerations suggest that photoinduced electron abstraction from appropriate biomaterials could compete with singlet oxygen production under in vivo conditions. This likely source of one electron-oxidized primary radicals, which can provide the precursors of the oxidative damage in phthalocyanine photosensitization, suggests the possibility of modulated toxicity by interaction with chemical additives. Examples of such additives recently studied are ascorbate, tocopherol and quercetin, all of which are natural antioxidants.

Animals↗
PubMed1995

Strategies for viral inactivation.

The risk of transmission of viruses and other pathogenic organisms by blood can be reduced but not eliminated through donor selection and screening methodologies. The safety of blood derivatives prepared from plasma pools from thousands of donors requires virus inactivation, without which transmission rates approach certainty and with which safety can exceed that of single-donor products. Current inactivation methods have reduced and possibly eliminated the transmission of enveloped viruses, eg, hepatitis B and C viruses and HIV; newer methods, when coupled with existing methods, have the likelihood of providing products whose safety matches that of any pharmaceutical product. Success with the virus inactivation of pooled blood products has fostered research into inactivation methods that are compatible with erythrocyte concentrates and platelet concentrates. The most advanced of these employ light-activatable compounds. If successful, virtually all blood products can be free from transmitting viruses and other pathogenic organisms.

Antiviral Agents↗
PubMed1995

Biodistribution and virus inactivation efficacy of a silicon phthalocyanine in red blood cell concentrates as a function of delivery vehicle.

The silicon phthalocyanine, HOSiPcOSi(CH3)2(CH2)3N(CH3)2 (Pc 4), is a new photosensitizer that can inactivate lipid-enveloped viruses in red blood cell concentrates (RBCC) upon exposure to red light. Because Pc 4 is insoluble in water, it was delivered either as an emulsion in saline and cremophor EL (CRM) or as a solution in dimethyl sulfoxide (DMSO). In RBCC, Pc 4 added in either vehicle distributed between the plasma and red blood cells (RBC) in a ratio of 4:6, similar to the ratio of these components in RBCC 3:7 (i.e. a hematocrit of 70%). Light exposure did not affect this distribution and caused only marginal degradation of Pc 4 at a light dose that inactivates > 5 log10 vesicular stomatitis virus (VSV). Among human plasma proteins, Pc 4 bound mainly (about 70%) to lipoproteins and to a lesser extent to albumin and lower molecular weight proteins when delivered in DMSO. When delivered in CRM, distribution between lipoproteins and albumin became more even. Among the lipoproteins Pc 4 bound almost exclusively to very low-density lipoproteins (VLDL) when delivered in DMSO and to both VLDL and low-density lipoproteins when added in CRM. The rate of VSV inactivation was independent of the delivery vehicle but there was less RBC damage, as measured by hemolysis during storage, when Pc 4 was added in CRM. These results indicate that using CRM as emulsifier can enhance the specificity of Pc 4-induced photochemical decontamination of RBCC for transfusion.

Animals↗
PubMed1995

The effect of irradiance on virus sterilization and photodynamic damage in red blood cells sensitized by phthalocyanines.

Phthalocyanines are being studied as photosensitizers for virus sterilization of red blood cells (RBC). During optimization of the reaction conditions, we observed a marked effect of the irradiance on production of RBC damage. Using a broad-band light source (600-700 nm) between 5 and 80 mW/cm2, there was an inverse relationship between irradiance and rate of photohemolysis. This effect was observed with aluminum sulfonated phthalocyanine (AlPcSn) and cationic silicon (HOSiPc-OSi[CH3]2[CH2]3N+[CH3]3I- phthalocyanine (Pc5) photosensitizers. The same effect occurred when the reduction of RBC negative surface charges was used as an endpoint. Under the same treatment conditions, vesicular stomatitis virus inactivation rate was unaffected by changes in the irradiance. Reduction in oxygen availability for the photochemical reaction at high irradiance could explain the effect. However, theoretical estimates suggest that oxygen depletion is minimal under our conditions. In addition, because the rate of photohemolysis at 80 mW/cm2 was not increased when irradiations were carried out under an oxygen atmosphere this seems unlikely. Likewise, formation of singlet oxygen dimoles at high irradiances does not appear to be involved because the effect was unchanged when light exposure was in D2O. While there is no ready explanation for this irradiance effect, it could be used to increase the safety margin of RBC virucidal treatment by employing exposure at high irradiance, thus minimizing the damage to RBC.

Erythrocytes↗
PubMed1995

Inactivation of Trypanosoma cruzi trypomastigote forms in blood components by photodynamic treatment with phthalocyanines.

Three phthalocyanine dyes HOSiPcOSi(CH3)2(CH2)3N(CH3)2 (Pc 4), HOSiPcOSi(CH3)2(CH2)3N+(CH3)3I- (Pc 5) and aluminum tetrasulfophthalocyanine hydroxide (AlOHPcS4) were evaluated for their ability to inactivate the trypomastigote form of Trypanosoma cruzi in fresh frozen plasma (FFP) and red blood cell concentrates (RBCC). The compound Pc 4 was found to be highly effective in killing T. cruzi, Pc 5 less effective and AlOHPcS4 ineffective. With FFP as the medium, a complete loss of parasite infectivity in vitro (> or = 5 log10) was found to occur with 2 microM Pc 4 after irradiation with red light (> 600 nm) at a fluence of 7.5 J/cm2, while with RBCC as the medium, a complete loss was found to occur at a fluence of 15 J/cm2. Even without illumination, Pc 4 at 2 microM also killed about 3.7-4.1 log10 of T. cruzi in FFP during 30 min. Observed differences in T. cruzi killing by the various phthalocyanines may related to differences in binding; Pc 4 binds to the parasites about twice as much as Pc 5. Ultrastructural analysis of treated parasites suggests that mitochondria are a primary target of this photodynamic treatment. The data indicate that Pc 4 combined with exposure to red light could be used to eliminate bloodborne T. cruzi parasites from blood components intended for transfusion. The inactivation of T. cruzi by Pc 4 in the dark suggests a possible therapeutic application.

Animals↗
PubMed1995

Psoralen-mediated virus photoinactivation in platelet concentrates: enhanced specificity of virus kill in the absence of shorter UVA wavelengths.

Treatments with psoralens and long-wavelength ultraviolet radiation (UVA, 320-400 nm; PUVA) have shown efficacy for virus sterilization of platelet concentrates (PC). Our laboratory has employed the psoralen derivative 4'-aminomethyl-4,5',8-trimethylpsoralen (AMT), and we have found that platelet integrity is best preserved when rutin, a flavonoid that quenches multiple reactive oxygen species, is present during AMT/UVA treatment of PC. In this report, we examine the effects of different UVA spectra under our standard PC treatment conditions (i.e. 50 micrograms/mL AMT, 0.35 mM rutin and 38 J/cm2 UVA). Added vesicular stomatitis virus (VSV; > or = 5.5 log10) was completely inactivated with the simultaneous maintenance of the platelet aggregation response (> 90% of control) when a UVA light source with transmission mainly between 360 and 370 nm (narrow UVA1) was used. In contrast, with a broad-band UVA (320-400 nm; broad UVA) light source, the aggregation response was greatly compromised (< 50% of control) with only a minor increase in the rate of VSV kill. With this lamp, platelet function could be improved to about 75% of the control by adding a long-pass filter, which reduced the transmission of shorter (< or = 345 nm) UVA wavelengths (340-400 nm; UVA1). At equivalent levels of virus kill, aggregation function was always best preserved when narrow UVA1 was used for PUVA treatment. Even in the absence of AMT, and with or without rutin present, narrow UVA1 irradiation was better tolerated by platelets than was broad UVA.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Platelets↗
PubMed1994

Photodynamic inactivation of herpes viruses with phthalocyanine derivatives.

The antiviral photosensitization capacity of 11 different phthalocyanine (Pc) derivatives was examined using herpes simplex virus-1, herpes simplex virus-2 and varicella zoster virus in the search for the most potent sensitizers for viral decontamination of blood. The kinetics of viral photoinactivation were resolved during the stages of viral adsorption and penetration into the host cells. The capacity of Pc in the photodynamic inactivation of viruses was compared with that of merocyanine 540 (MC540), another widely studied photosensitizer. Sensitivity to photoinactivation decreased progressively with time after addition of viruses to their host cells. The viruses were most sensitive to photodynamic inactivation up to 30 min from the initiation of adsorption. Cell-associated viruses, 45-60 min after the onset of adsorption, are highly resistant to photodynamic treatment by most photosensitizers, with the exception of amphiphilic Pc derivatives. Thus the mixed sulfonated Pc-naphthalocyanine derivatives AlNSB3P and AlN2SB2P demonstrated a remarkable decontamination activity even 60 min after the onset of adsorption. Ultrastructural examination of these photosensitized viruses demonstrated damage to the viral envelope which prevented viral adsorption and/or penetration. The non-enveloped adenovirus was found to be resistant to all the dyes tested.

Adenoviruses, Human↗
PubMed1994

Quencher-enhanced specificity of psoralen-photosensitized virus inactivation in platelet concentrates.

BACKGROUND: Treatment with psoralens and UVA (PUVA) has been shown to be efficacious in eliminating the risk of virus transmission by platelet concentrates (PCs). It has previously been demonstrated that, during the inactivation of cell-free vesicular stomatitis virus (VSV) by aminomethyltrimethylpsoralen (AMT) and UVA in PCs, platelet function could be protected either by oxygen removal before irradiation or by inclusion of a type I free radical quencher, such as mannitol. STUDY DESIGN AND METHODS: Under previous PUVA treatment conditions for PCs (25 micrograms/mL AMT; 30 min UVA at 7 mW/cm2; 2 mM [2 mmol/L] mannitol), more than 6 log10 of added cell-free VSV was completely inactivated. In the current study, various PUVA conditions are evaluated for efficacy in inactivating other viral forms that could be present in PCs. Maintenance of platelet integrity (i.e., platelet number, solution pH, and aggregation response during initial storage after treatment) and kill of cell-associated VSV are examined. RESULTS: While cell-free viruses were inactivated efficiently under previous PUVA conditions, cell-associated VSV and the non-lipid-enveloped bacteriophage M13 were not. Effective inactivation of these viruses was achieved by raising the concentration of AMT to 50 micrograms per mL and extending the period of irradiation to 90 minutes (39 J/cm2). However, for maintenance of platelet integrity under these conditions, the prior removal of oxygen or the inclusion of compounds known to quench both type I and type II photoreactants (e.g., flavonoids such as rutin) was required. CONCLUSION: These findings suggest that the viral safety of PCs may be enhanced through treatment with AMT and UVA in the presence of flavonoids, and that flavonoid use may prove beneficial in other systems where oxygen-mediated damage occurs.

Antiviral Agents↗
PubMed1994

New phthalocyanines for photodynamic virus inactivation in red blood cell concentrates.

Cationic phthalocyanines with either aluminum or silicon as the central metal were evaluated for their ability to inactivate viruses in red blood cell concentrates (RBCC) photodynamically. In addition, the virucidal potential of a substituted anionic phthalocyanine, aluminum dibenzodisulfophthalocyanine hydroxide (A1N2SB2POH) was evaluated and compared with that of the much studied anionic aluminum tetrasulfophthalocyanine hydroxide (A1PcS4OH). Based on the rate of inactivation of the lipid-enveloped vesicular stomatitis virus (VSV), the virucidal potential of these phthalocyanines was: HOSiPcOSi(CH3)2(CH2)3N+(CH3)3I- (Pc 5) = SiPc[OSi(CH3)2-(CH2)3N+(CH3)3I-]2 (Pc 6) > A1PcOSi(CH3)2(CH2)3N+(CH3)2(CH2)11CH3I- (Pc 21) = A1N2SB2POH = A1PcS4 > HOSiPc[OSi(CH3)2(CH2)3N+(CH3)2(CH2)11CH3I-]2 (Pc 14) > A1PcOSi(CH3)2(CH2)3N+(CH3)3I- (Pc 2). Phthalocyanine ligand 14 and Pc 21 are new phthalocyanines, made by quaternizing known amino analogues. Compared to VSV, the rate of inactivation of Sindbis virus (another model lipid-enveloped virus) was identical when treated in red blood cells (RBC) with Pc 5 and slightly higher when treated with Pc 6 and A1PcS4OH. Treatment of RBCC containing cell-free human immunodeficiency virus (HIV-1) with Pc 5 or A1PcS4OH required 15 min of irradiation to inactivate (> 5 log10 reduction) the virus. The extent of HIV-1 inactivation with A1N2SB2POH was 3.7 log10 after 60 min of red light exposure. The RBC integrity after photosensitization was measured by the ability of the cells to bind to plates coated with poly-L-lysine, (which reflects the retention of the RBC surface negative charges) and hemolysis of the cells over a 7 day storage period.(ABSTRACT TRUNCATED AT 250 WORDS)

Erythrocyte Transfusion↗
PubMed1994

The photochemical properties of fluoroaluminum phthalocyanine.

Fluoride is known to inhibit the photodynamic activity of aluminium phthalocyanine in a variety of biological systems. In order to gain insight into this phenomenon, the effect of fluoride on the photophysical properties of free and albumin-bound chloroaluminum phthalocyanine sulfonate (AlPcSn) were studied. The association constant of NaF with AlPcSn in aqueous solution was measured as 500 +/- 20 M-1. This binding affects the photophysical properties of the dye: the absorption bands in the visible range are blue-shifted by 6-8 nm, and this effect is mirrored in the fluorescence emission spectrum. Human serum albumin significantly quenched the dye fluorescence independent of the presence of fluoride ion. The transient absorption spectrum of the excited dye triplet is unchanged by NaF, but the quantum yield for its generation is increased by 50%, with no decrease in its lifetime. Formation of fluoroaluminum phthalocyanine complexes was also observed in tetrabutylammonium fluoride-assisted solutions in wet acetonitrile. The fluoro-AlPcSn complex is a better photosensitizer for generation of singlet oxygen than the original dye-hydroxyl ion complex, as confirmed using the imidazole-N,N-dimethyl-4-nitrosoaniline method. On the other hand, the fluoro-AlPcSn complex exhibits an intense inhibitory effect on photohemolysis of red blood cells (RBC) even after the cells are washed to remove free dye and fluoride prior to irradiation, indicating that once the dye is attached to the cellular site, the fluoride ligand is no longer prone to displacement (by hydroxyl ion, for example). Nonetheless, it is clear from the spectroscopic data that the new fluoro complex is an efficient sensitizer for photooxidation.(ABSTRACT TRUNCATED AT 250 WORDS)

Aluminum↗
PubMed1994

Aluminium phthalocyanines-induced photolysis of human vascular wall cells in culture and the effect of fluoride on photodynamic action.

BACKGROUND: Phthalocyanines, second-generation photosensitizers with several attractive properties for use in photodynamic therapy, have been shown to accumulate in malignant lesions and atherosclerotic plaques. After exposure of phthalocyanines-loaded tissues to visible light, the targeted cells become injured and eventually die. In vitro, when fluoride is added before exposure to the light, it can protect some cell types against photodynamic action sensitized by chloroaluminium phthalocyanine (AIPc) and its derivatives. METHODS: The effect of 50 mumol/l chloroaluminium phthalocyanine tetrasulfonate (AIPcS4) and 5 mumol/l AIPc, with and without the addition of 5 mumol/l NaF, on the viability of cultured human endothelial cells (HuEC), human smooth muscle cells (HuSMC), and skin fibroblasts (HuSF) was examined. A 150 W quartz halogen light bulb equipped with a cut-off filter (lambda > 605 nm) was used to activate the phthalocyanines. Cell viability was examined 24 h after irradiation by staining of the cells with fluorescein diacetate/ethidiumbromide and by counting the number of attached cells with a cell counter. RESULTS: In the case of AIPc, the viability of all cell types tested was reduced, in a dose-dependent manner, to about 50% of that of the corresponding controls for a maximum irradiation time of 600 s. When we used AIPcS4, both HuEC and HuSF were considerably less sensitive than HuSMC. The addition of fluoride to AIPc-loaded cells before exposure to light protected HuEC and HuSF, but not HuSMC. In the case of AIPcS4, with and without fluoride, only HuSMC were sensitive. CONCLUSIONS: The addition of fluoride to AIPc or the use of AIPcS4 without fluoride could be a valuable approach, selectively destroying HuSMC without affecting HuEC and HuSF, for the reduction of restenosis rates after recanalization of stenosed or occluded arteries. Moreover, because neither type of phthalocyanines causes cutaneous phototoxicity, these second-generation photosensitizers seem to be best suited to the photodynamic treatment of atherosclerosis.

Arteriosclerosis↗