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ABSTRACT: The perihydroxylated perylene quinone hypericin has been reported to possess potent anti-metastatic and antiangiogenic activities, generated by targeting diverse crossroads of cancer-promoting processes via unique mechanisms. Hypericin is the only known exogenous reagent that can induce forced poly-ubiquitination and accelerated degradation of heat shock protein 90 (Hsp90) in cancer cells. Hsp90 client proteins are thereby destabilized and rapidly degraded. Hsp70 client proteins may potentially be also affected via preventing formation of hsp90-hsp70 intermediate complexes. We show here that hypericin also induces enhanced degradation of hypoxia-inducible factor 1α (HIF-1α) in two human tumor cell lines, U87-MG glioblastoma and RCC-C2VHL-/- renal cell carcinoma and in the non-malignant ARPE19 retinal pigment epithelial cell line. The hypericin-accelerated turnover of HIF-1α, the regulatory precursor of the HIF-1 transcription factor which promotes hypoxic stress and angiogenic responses, overcomes the physiologic HIF-1α protein stabilization which occurs in hypoxic cells. The hypericin effect also eliminates the high HIF-1α levels expressed constitutively in the von-Hippel Lindau protein (pVHL)-deficient RCC-C2VHL-/- renal cell carcinoma cell line. Unlike the normal ubiquitin-proteasome pathway-dependent turnover of HIF-α proteins which occurs in normoxia, the hypericin-induced HIF-1α catabolism can occur independently of cellular oxygen levels or pVHL-promoted ubiquitin ligation of HIF-1α. It is mediated by lysosomal cathepsin-B enzymes with cathepsin-B activity being optimized in the cells through hypericin-mediated reduction in intracellular pH. Our findings suggest that hypericin may potentially be useful in preventing growth of tumors in which HIF-1α plays pivotal roles, and in pVHL ablated tumor cells such as renal cell carcinoma through elimination of elevated HIF-1α contents in these cells, scaling down the excessive angiogenesis which characterizes these tumors.
PLoS ONE 01/2011; 6(9):e22849. · 4.09 Impact Factor
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ABSTRACT: We developed a method for selectively propagating disease-related autoreactive T-cell lines (auTCLs) based on their increased resistance to apoptosis. The generated auTCLs homogeneously co-express CD45RO and CD49a, adhere strongly to extracellular matrix proteins and express high interleukin-17 (IL-17) messenger RNA levels, resembling a T-cell subset proposed to transmigrate into tissues and induce systemic and local inflammation in rheumatoid arthritis. The combinations of T-cell oligoclones that comprise probable multiple sclerosis (pMS) disease-related lines use a unique portfolio of T-cell receptor beta-chain variable allele (BV genes) combinations forming 'disease-specific cluster patterns'. The auTCL derived from different patients and from different myelin epitopes display striking similarities in BV gene allele clusters and are derived primarily from a disease-prone hotspot residing in the BV gene locus between Vbeta6 and Vbeta9. Conversely, healthy subject TCLs use different BV gene allele sets, forming 'healthy responder usage formats'. These formats were absent from the pMS patient V-beta gene allele combinations evaluated in this study. Hierarchical clustering of the BV gene combinations, distinguish three pMS auTCL groups, implying existence of up to three disease-related immune response patterns. These subgroup patterns may reflect different disease subclasses or alternatively they may suggest immune reactivity to different aetiological agents. Analyses of clonal-clustering patterns may potentially aid in subclassification of MS or in characterizing aetiological agents of this disease.
Immunology 11/2009; 128(2):287-300. · 3.32 Impact Factor
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ABSTRACT: Microbial biofilms are a major impediment to the use of indwelling medical devices, generating device-related infections with high morbidity and mortality. Major efforts directed towards preventing and eradicating the biofilm problem face difficulties because biofilms protect themselves very effectively by producing a polysaccharide coating, reducing biofilm sensitivity to antimicrobial agents. Techniques applied to combating biofilms have been primarily chemical. These have met with partial and limited success rates, leading to current trends of eradicating biofilms through physico-mechanical strategies. Here we review the different approaches that have been developed to control biofilm formation and removal, focusing on the utilization of acoustic energy to achieve these objectives.
Sensors 01/2009; 9(4):2538-54. · 1.74 Impact Factor
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ABSTRACT: Differential expression of apoptotic genes may influence the susceptibility of activated lymphocytes to expand and induce acute relapse and persistent inflammation in patients with relapsing-remitting multiple sclerosis (RRMS). The exact relationship between alterations in apoptotic-related gene expression and clinical disease activity has not been broadly evaluated. In this study we studied peripheral blood mononuclear cells (PBMCs) expression of pro- and antiapoptotic genes in RRMS patients during acute relapse in comparison to patients in remission. Using cDNA Affymetrix microarrays platform (U133A2 microarrays) we analyzed the gene expression profile of PBMC derived from 22 RRMS patients in acute relapse (15 females, mean age 34.6 +/- 1.8 years, disease duration 5.6 +/- 0.8 years) in comparison to 20 sex- and age-matched RRMS patients in remission. One thousand five hundred seventy-eight gene transcripts significantly differentiated acute multiple sclerosis (MS) relapse from remission. This characteristic gene expression signature was enriched by an apoptotic-related pathway. The 1578 gene transcripts that significantly differentiated acute relapse from remission were enriched by 55 apoptotic-related genes in that reflected different operating pathways during the acute phase of the disease. These genes mainly involved the caspase-dependent pathway and included overexpression of the negative regulator of FAS-induced apoptosis (TOSO) and the BCL2 antiapoptotic family members (BCL2, BCL2 AA) as well as downexpression of proapoptotic genes like BAX, apoptotic protease-activating factor 1 (APAF1) and caspases 1, 2, 8, 9. and 10. An additional group of antiapoptotic genes related to T cell receptor-mediated apoptosis was also found to be overexpressed in acute relapse and included TCR-binding CD3E antigen, antiapoptotic serine threonin kinase (AKT), and NF kappa B-associated genes like reticuloendotheliosis viral oncogene homolog A (RELA) and human T cell leukemia virus type I-binding protein (Tax1BP) known to inhibit tumor necrosis factor (TNF)-induced apoptosis. Our findings demonstrate impaired apoptotic mechanisms in peripheral lymphocytes from RRMS patients during acute relapse. This suggests that the inflammatory process in active disease is targeted by inhibition of proapoptotic and repression of antiapoptotic genes that allow prolonged abnormal immune responses.
Annals of the New York Academy of Sciences 07/2007; 1107:155-67. · 3.15 Impact Factor
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ABSTRACT: Low-energy surface acoustic waves generated from electrically activated piezo elements are shown to effectively prevent microbial biofilm formation on indwelling medical devices. The development of biofilms by four different bacteria and Candida species is prevented when such elastic waves with amplitudes in the nanometer range are applied. Acoustic-wave-activated Foley catheters have all their surfaces vibrating with longitudinal and transversal dispersion vectors homogeneously surrounding the catheter surfaces. The acoustic waves at the surface are repulsive to bacteria and interfere with the docking and attachment of planktonic microorganisms to solid surfaces that constitute the initial phases of microbial biofilm development. FimH-mediated adhesion of uropathogenic Escherichia coli to guinea pig erythrocytes was prevented at power densities below thresholds that activate bacterial force sensor mechanisms. Elevated power densities dramatically enhanced red blood cell aggregation. We inserted Foley urinary catheters attached with elastic-wave-generating actuators into the urinary tracts of male rabbits. The treatment with the elastic acoustic waves maintained urine sterility for up to 9 days compared to 2 days in control catheterized animals. Scanning electron microscopy and bioburden analyses revealed diminished biofilm development on these catheters. The ability to prevent biofilm formation on indwelling devices and catheters can benefit the implanted medical device industry.
Antimicrobial Agents and Chemotherapy 01/2007; 50(12):4144-52. · 4.84 Impact Factor
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ABSTRACT: Autologous stem cell transplantation is being considered as treatment of severe refractory autoimmune disorders, including MS. Stem cell mobilization is achieved with granulocyte-colony stimulating factor (G-CSF), however, G-CSF administration resulted in cases of worsened clinical MS status. We studied autoreactive T-cell properties, which can promote CNS inflammation in MS. We show that G-CSF enhances MS autoreactive T cell line adhesion to the ECM proteins collagen IV and fibronectin as effectively as the proinflammatory IFNgamma and TNFalpha, known to exacerbate MS symptoms. We propose a link between clinical worsening of MS symptoms induced by G-CSF and the hyperstimulation of T cell adhesion to ECM elicited by G-CSF.
Journal of Neuroimmunology 04/2006; 172(1-2):145-55. · 2.96 Impact Factor
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ABSTRACT: Multiple sclerosis (MS) is an autoimmune disease where T-cells activated against myelin antigens are involved in myelin destruction. Yet, healthy subjects also harbor T-cells responsive to myelin antigens, suggesting that MS patient-derived autoimmune T-cells might bear functional differences from T-cells derived from healthy individuals. We addressed this issue by analyzing gene expression patterns of myelin oligodendrocytic glycoprotein (MOG) responsive T-cell lines generated from MS patients and healthy subjects. We identified 150 transcripts that were differentially expressed between MS patients and healthy controls. The most informative 43 genes exhibited > 1.5-fold change in expression level. Eighteen genes were upregulated including BCL2, lifeguard, IGFBP3 and VEGF. Twenty five genes were down-regulated, including apoptotic activators like TNF and heat shock protein genes. This gene expression pattern was unique to MOG specific T-cell lines and was not expressed in T-cell lines reactive to tetanus toxin (TTX). Our results indicate that activation in MS that promotes T-cell survival and expansion, has its own state and that the unique gene expression pattern that characterize autoreactive T-cells in MS represent a constellation of factors in which the chronicity, timing and accumulation of damage make the difference between health and disease.
Clinical and Developmental Immunology 09/2005; 12(3):203-9. · 1.84 Impact Factor
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ABSTRACT: The purpose of this study is to demonstrate feasibility of using our novel concept, termed competitive quenching, for protecting the choroidal extravascular compartment and retinal pigment epithelium (RPE) from verteporfin (VP)-induced phototoxicity using hypericin. Furthermore, we aim to achieve partitioning of the quencher, hypericin, in the extravascular space and VP within the microvascular compartment of the chorio-retinal complex in vivo.
We protect RPE cells from damage inflicted by photoactivated VP by introducing hypericin into these cells prior to photosensitization to quench the photosensitizing activity of VP. Cell protection levels were measured by MTT and Hemacolor viability assays. Wavelength range used for VP photoexcitation (700 +/- 40 nm) excludes the absorption range of hypericin, preventing the latter from photoactivation. Pharmacokinetic conditions, in which hypericin spreads throughout the choroidal and retinal extravascular space while VP is confined to the vasculature, are delineated using double-fluorescence imaging.
Cell viability increased 3- to 5-fold when 10-20 microM hypericin were present in RPE cells during photosensitization with 0.1-0.5 microM VP. VP fluorescence intensity was unchanged by the presence of hypericin in the cells. Hypericin administered intravenously to rats was confined to the choroidal vasculature after 15 min to 2 hr. Subsequently, hypericin partitioned to the choroidal and retinal extravascular space. VP administered at this time was confined to the microvasculature.
RPE and choroid may potentially be protected by compartmentalizing hypericin to the extravascular compartment while VP administered shortly before photosensitization is confined to the microvasculature. Adverse photodynamic therapy (PDT) damage to choroidal tissues adjacent to neovasculature targeted for photoablation have the potential of being prevented by competitive quenching with hypericin.
Current Eye Research 05/2005; 30(4):269-77. · 1.28 Impact Factor
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ABSTRACT: Hypericin, a perihydroxylated dianthraquinone is shown here to be a highly potent inhibitor of angiogenesis in several ocular models examined in rat eyes. Extensive angiogenesis induced in the cornea and iris by intra-ocular administration of FGF-2 was effectively inhibited by a minimum of four dose regimens of hypericin (2 mg/kg) administered via the intraperitoneal route at 48 h intervals. Maximal inhibition was achieved when animal treatment with hypericin was initiated 48 h prior to inoculation of FGF-2. The molecular basis for the hypericin-mediated inhibition of angiogenesis in the anterior eye compartment appears to involve several sites in the cascade leading to angiogenesis. We show that the activating phosphorylation of extracellular signal-regulated MAP kinases (ERK1/2) is inhibited by hypericin in human retinal pigment epithelial cells and in EA.hy926 cells, an endothelial hybridoma expressing endothelial cell properties. ERK1/2 activity is required for the transactivation of hypoxia-inducible factor 1 alpha (HIF-1alpha) and in VEGF-induced blood vessel sprouting. MT1-MMP activity in human microvascular endothelial cells was also inhibited. The findings identify hypericin as a potentially useful agent in the treatment of ophthalmic neovascularization pathogeneses.
Angiogenesis 02/2005; 8(1):35-42. · 6.06 Impact Factor
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ABSTRACT: Multiple sclerosis is an autoimmune central nervous system disease that affects young adults and causes inflammation, demyelination and axonal loss. Within the common relapsing-remitting course of the disease patients develop various neurological symptoms that lead to significant disability overtime. The anti-phospholipid syndrome, similarly to multiple sclerosis, appears in young adults and is characterized by thromboembolic events and pregnancy complications. The overlay between these two diseases and the ability to correctly diagnose or differentiate between them is sometimes difficult. The current review approaches this problem and discusses whether multiple sclerosis and anti-phospholipid syndrome are actually one or two diseases.
Harefuah 11/2004; 143(10):724-6, 766, 765.
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ABSTRACT: A unique property of the photodynamic signal transduction inhibitor hypericin (HY) is high functionality in the dark, which has been shown to result in portfolio of anticancer activities both in vitro and in vivo. Here we show that treatment with HY significantly reduces growth rate of metastases in 2 murine models: breast adenocarcinoma (DA3) and squamous cell carcinoma (SQ2). Focus on metastases was achieved by resection of primary tumors at stages in which micrometastases exist in lungs. Long-term animal survival in DA3 tumor-excised groups increased from 15.6% in controls to 34.5% following supplementary treatment with HY. In mice bearing SQ2 tumor metastases, therapy with HY increased animal survival from 17.7% in controls to 46.1%. Using Laser-induced fluorescence and multipixel spectral image analyses, we demonstrate that HY has a high tendency to accumulate in primary and metastatic tumors; HY content in lungs bearing metastases was approximately 2-fold higher than in the lungs of healthy animals. The tendency of HY to preferentially concentrate in lung metastases, combined with its potent antiproliferative activities, may render HY as a useful supplementary modality in the treatment of metastatic cancer irrespective of photoactivation.
International Journal of Cancer 10/2004; 111(4):596-603. · 5.44 Impact Factor
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ABSTRACT: Multiple sclerosis (MS) is a central nervous system disease with an unpredictable course and outcome. Peripheral blood mononuclear cells (PBMCs) are involved in the disease pathogenesis and induce active demyelination. Using oligonucleotide microarrays, we identified a statistically significant transcriptional signature of 1,109 genes in PBMCs from 26 MS patients, irrespective of disease activation state or immunomodulatory treatment. This signature contains genes that implicate underlying processes involved in MS pathogenesis including T-cell activation and expansion, inflammation, and apoptosis. Another transcriptional signature of 721 genes involved in cellular recruitment, epitope spreading, and escape from regulatory immune surveillance identified MS patients in acute relapse compared with remission. Our results offer new opportunity for understanding the mechanisms involved in MS and indicate that gene expression patterns in PBMCs contain information about a remote-target disease process that may be useful for diagnosis and future tailoring of therapeutic strategies for MS.
Annals of Neurology 04/2004; 55(3):410-7. · 11.09 Impact Factor
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ABSTRACT: Pediatric cardiopulmonary bypass involves the creation of a large obligatory priming reservoir. Packed red blood cells are an essential part of the cardiopulmonary bypass priming solution in children. The storage media in packed red blood cells might cause significant acid-base, glucose, and electrolyte imbalances, which have been associated with severe complications. The purpose of the present study was to evaluate the metabolic effects of fresh (< or =5 days) versus old (>5 days) stored packed red blood cells added to the priming solutions of pediatric patients undergoing cardiac surgery.
Blood samples were drawn from cardiopulmonary bypass priming of 30 consecutive pediatric patients undergoing cardiac surgery. Patients were divided into 2 groups. Fresh (< or =5 days old) stored packed red blood cells were added to the priming solution in group 1, and old (>5 days old) stored packed red blood cells were added to the priming solution in group 2. In each group blood samples were drawn from the packed red blood cells on arrival to the operating room and from the priming solution immediately after packed red blood cells were added and after 20 minutes of prime circulation. Samples were also collected at the beginning of cardiopulmonary bypass and after 30 minutes. The last sample was collected on arrival to the pediatric intensive care unit. The levels of potassium, glucose, and lactate and the acid-base balance were analyzed in each sample.
There was a linear increase in potassium levels in packed red blood cell samples with increasing packed red blood cell age, ranging from 5.4 to 18.4 mEq/L. Significant differences in the concentrations of potassium, glucose, and lactate and the acid-base balance were found when comparing old and fresh packed red blood cells in samples taken during the packed red blood cell and early prime time. Those differences resolved after 20 minutes of reconstitution of the priming solution. The age of the packed red blood cells had no effect on the samples taken during bypass and those taken in the pediatric intensive care unit.
The significantly higher concentration of potassium and lactate and lower pH in old stored packed red blood cells has a minimal effect on the final constitution of priming solution before and during cardiopulmonary bypass in children undergoing corrective cardiac surgery.
Journal of Thoracic and Cardiovascular Surgery 04/2004; 127(4):949-52. · 3.41 Impact Factor
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ABSTRACT: T cells that are autoreactive against myelin antigens play a pivotal role in the pathogenesis of multiple sclerosis (MS). The concept of T cell vaccination (TCV) has been developed to generate an immune response against these autoreactive pathogenic T cells. Immunologic data accumulated so far demonstrates depletion of T cells reactive against immunodominant myelin peptides after immunization in the animal model of experimental autoimmune encephalomyelitis, as well as in vaccinated MS patients. Clinical trials have confirmed the safety and efficacy of TCV in a small number of immunized MS patients. TCV resulted in reduced relapse rates and slowed the progression of neurological disability and MRI brain lesion load. Recently, there have been several double-blind, placebo-controlled studies initiated to evaluate the role of TCV in MS. Specifically, it is important to examine the effect of early TCV, given after the first episode suggestive of the disease, in order to prevent the process of epitope spreading.
Autoimmunity Reviews 02/2004; 3(1):25-32. · 6.62 Impact Factor
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ABSTRACT: A unique property of the photodynamic signal transduction inhibitor hypericin is functionality in the dark. We show in tumor cells that hypericin targets the heat shock protein (Hsp) 90 chaperone but not Hsp70 (Hsc70) to enhanced ubiquitinylation. As a consequence Hsp90 chaperone functionality is abrogated and the client proteins, mutant p53, Cdk4, Raf-1, and Plk, are displaced from complexes with Hsp90, destabilized, and degraded via a proteasome-independent pathway. Decline in Raf-1 prevents downstream activation of extracellular signal-regulated kinase 1/2 kinases, the Ras/Raf pathway is inhibited, and tumor cell proliferation is arrested. The cells exhibit multiple aberrations including retardation at G(2)-M, increased cell volume, and multinucleation, all of which are hallmarks of mitotic cell death. The studies demonstrate that ubiquitinylation of Hsp90 inactivates the chaperone, destabilizes the plethora of client proteins, and creates deficiencies in multiple unrelated cellular functions. This combination constitutes a mechanism by which hypericin generates mitotic cell death in cancer cells.
Cancer Research 01/2004; 63(23):8241-7. · 7.86 Impact Factor
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ABSTRACT: Multiple sclerosis (MS), a chronic demyelinating disease, is thought to be initiated by pathogenic T cells that transmigrate the vascular endothelium and enter the brain through vascular and parenchymal basement membranes (BM). Vaccination with T-cell lines reactive with myelin basic protein (MBP) and myelin oligodendrocytic glycoprotein (MOG) epitopes, expanded with interleukin-2 (IL-2), and attenuated by ionizing radiation is currently being evaluated as a therapeutic modality for this disease. We examined mechanisms potentially involved in pathogenic cell migration into the central nervous system (CNS) and the influence of irradiation on these processes. Seven of 7 autoantigen-responsive T-cell lines from MS patients adhered to collagen IV, the major collagenous constituent of BMs. This adhesion was inhibited almost completely by monoclonal antibody (MAb) to very late antigen (VLA)-1 and partially by anti-VLA-2. T-cell lines from healthy donors adhered more variably to collagen IV. Furthermore, patient derived T cells actively transmigrated through a collagen IV gel toward medium containing TNF-a, in a process that was inhibited by MAbs to VLA-1. Ionizing radiation at the dose used in vaccine preparation, inhibited morphological polarization associated with migratory capability, induced integrin clustering on the cell membrane, and abrogated adhesion to collagen IV. These findings may have important implications for understanding the pathogenesis of MS and how irradiation of potentially pathogenic T cells produces a reagent with possible therapeutic effects in T-cell vaccination (TCV).
Journal of Clinical Immunology 06/2002; 22(3):153-63. · 3.08 Impact Factor
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ABSTRACT: The potent photodynamic properties of hypericin (HY) elicit a range of light-dependent virucidal and tumoricidal activities. Yet, a relatively low reduction/oxidation potential endows HY with electron accepting and donating properties enabling it to act as both an oxidizing and a reducing agent. HY can thus compete as an electron acceptor from bioenergized reduction/oxidation reactions generating its excitation energy for biological activities from physiological reduction/oxidation reactions in the absence of light. Our studies show that HY can inhibit the growth of highly metastatic murine breast adenocarcinoma and squamous cell carcinoma tumors in culture. Furthermore, we show that HY can interfere with the growth of these tumors in mice reducing tumor size and prolonging animal survival in complete absence of light. While there is no evidence that HY induces apoptosis in these cells in the dark, 3H-thymidine incorporation into DNA was significantly reduced indicating effects that are apparently cytostatic in nature compared to the cytocidal effects of HY with light.
Photochemistry and Photobiology 07/2001; 74(2):120 - 125. · 2.41 Impact Factor
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ABSTRACT: Photodynamically induced virus inactivation appears promising in preventing transmission of enveloped virus infections in transfusible blood products. The potential for utilizing hypericin as a photosensitizer to inactivate key enveloped viruses in packed red cell concentrates (PRC) was evaluated. In addition to inactivating effectively ≥106 TCID50 of human immunodeficiency virus (HIV), inactivation of bovine viral diarrhea virus (BVDV) in PRC was used as a model for hepatitis C virus to overcome the deficiency in reliable experimental systems for hepatitis C virus (HCV) inactivation. BVDV was two orders of magnitude more sensitive to inactivation by hypericin than HIV. As part of the virucidal efficacy analyses, the effects of photosensitization on hemopoietic cell lines carrying quiescent integrated HIV provirus were studied as models for evaluating virus inactivation in latently infected cells. Phorbol ester-induced virus production by these cells was effectively prevented by photosensitization with hypericin. A refinement of the illumination conditions, incorporating a monochromatic sodium light source with an emission spectrum coinciding with the absorption peak of hypericin, was highly virucidal, however, caused unacceptable levels of hemolysis. Red blood cells could be protected from phototoxic cellular damage by complexing hypericin with human serum albumin (albumin–hypericin), but the decrease in hemolysis was at the expense of virucidal efficacy. Thus, excitation of hypericin with a fluorescent source appears to be useful potentially for virus inactivation in PRC.
Photochemistry and Photobiology 01/2000; 71(2):188 - 195. · 2.41 Impact Factor
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Gad Lavie,
Tilda Barliya, Mathilda Mandel,
Michael Blank,
Yonina Ron,
Arie Orenstein,
Tami Livnat,
Noga Friedman,
Lev Weiner,
Mordechai Sheves,
Dov Weinberger
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ABSTRACT: Incorporation of photodynamic therapy into clinical practice for induction of vascular photo-occlusion highlights the need to prevent adverse phototoxicity to sensitive juxtaposed tissues, particularly in the retina. We developed a system termed "competitive quenching" to prevent adverse phototoxic damage. It involves differential compartmentalization of a photoactivator to the intravascular compartment for photoexcitation and delivery of phototoxicity to targeted vessels. A different photodynamic agent is partitioned to the extravascular retinal space to quench reactive oxygen species generated by photosensitization, thereby protecting the adjacent retinal tissues from adverse phototoxicity. The absorption spectra of quenchers must span wavelengths that are shorter and excluded from the spectral range of photoexcitation light to prevent photoactivation of the quencher. Perihydroxylated perylenequinones were found to be suitable to function as "competitive quenchers" with the prototype hypericin identified as a potent quencher. Here we examined the mechanisms operative in competitive quenching and suggest that hypericin forms a complex with verteporfin, thereby quenching singlet oxygen formation. Furthermore, we show that hypericin, with six phenolic hydroxyls, protects retinal and endothelial hybridoma cells from phototoxicity more effectively than the dimethyl tetrahydroxy helianthrone structural analog with only four such phenolic hydroxyls. The findings suggest that hydroxyl numbers contribute to the efficacy of competitive quenching.
Photochemistry and Photobiology 83(5):1270-7. · 2.41 Impact Factor
