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PubMedDate not supplied

Extensive burns caused by the abusive use of photosensitizing agents.

Psoralens are photosensitizing agents used in dermatology as reinforcements in psoralen ultraviolet A-range therapy. We report observations of 14 young women hospitalized for severe burns caused by abusive use of psoralens. The burns were of superficial and deep second-degree depth and covered more than 76% of the body surface on average. All patients needed fluid resuscitation. Hospital stay was 11 days on average. Healing was obtained without skin grafting in all cases. Among the six patients who responded to the mailed questionnaire, negative effects are now present in all patients as inflammatory peaks. Two patients have esthetic sequelae such as dyschromia and scars. The misuse of photosensitizing agents poses many problems. These accidents are very expensive. The largeness of the burned surface can involve a fatal prognosis. And finally, one can suspect that a much larger portion of the population regularly uses these products without any serious accident. In this case carcinogenesis can be expected.

Adolescent↗
PubMed1994

Studies on inactivation of pathogenic microorganisms in culture media and in bovine semen by photosensitive agents.

The application of three photosensitive agents for disinfection of bovine semen was investigated. Bovine microbial pathogens suspended in tissue culture medium and/or PBS and also added to bovine semen were exposed to the photosensitive agents followed by irradiation. Hematoporphyrin, hematoporphyrin derivative and thiopyronine were effective against bovine herpes virus-1, bovine viral diarrhoea virus, Mycoplasma bovigenitalium, Mycoplasma canadense, and Ureaplasma diversum in culture media. In addition, thiopyronine was effective against Leptospira pomona. Similar treatments were not effective against Leptospira hardjo, Mycoplasma bovis, or Campylobacter fetus subsp. venerealis. When microorganisms were added to bovine semen, only bovine herpes virus-1 was controlled by the photosensitive agents used at concentrations which did not appear harmful to sperm cells.

Animals↗
PubMed1995

Effect of density-gradients on the binding of photosensitizing agents to plasma proteins.

The binding of photosensitizing agents to low-density lipoprotein is considered an important factor in tumor localization. We examined the affinity of a group of photosensitizers, varying in charge and hydrophobicity, for LDL, under conditions designed to determine whether the high salt concentration involved in conventional KBr gradients affected the results. Density-gradients containing KBr vs D2O were evaluated; the latter can delineate VLDL and LDL from other plasma components, while the KBr gradient readily resolved VLDL, LDL, HDL and albumin. Distribution of the photosensitizers to plasma fractions was assessed, along with the effect of Cremophor EL, an emulsifier used for formulation of water-insoluble drugs. Both the D2O and KBr gradients provided similar results with regard to the affinity of anionic, neutral or cationic photosensitizers for LDL. The use of Cremophor EL for drug formulation was associated with an altered electrophoretic lipoprotein profile. In some cases, affinity of CRM-solubilized sensitizers for plasma components varied with the density-gradient employed. The high salt concentration used in density-gradient fractionation had little effect on the affinity of photosensitizing agents to low-density lipoprotein but may introduce artifacts when emulsifiers are used in drug formulation.

Blood Proteins↗
PubMed1993

Photodynamic therapy of squamous cell carcinoma. An evaluation of a new photosensitizing agent, benzoporphyrin derivative and new photoimmunoconjugate.

Photodynamic therapy for cancer depends on the relatively selective distribution of photosensitizing agents to malignant as compared with normal tissues, rendering the malignant cells more susceptible to light-mediated damage. Photodynamic therapy has been used with only moderate success to date. The purpose of this study was to compare a new photosensitizing agent, benzoporphyrin derivative (BPD), to the standard agent presently in use, photofrin II, in a hamster cheek pouch model of squamous cell carcinoma. As well we have investigated the potential of using a tumour-specific monoclonal antibody-BPD conjugate to improve the tumour localizing properties of BPD. Treatment consisted of photodynamic therapy with either photofrin II, BPD, or a tumour-specific anti-epidermal growth factor receptor-BPD conjugate. Control groups of light alone, anti-EGFr, tumour non-specific MoAb, and tumour non-specific MoAb-BPD conjugate were included with the contralateral cheek pouch of each animal acting as a dark control. An assessment of differential delivery of BPD to tumour and to normal mucosa was undertaken using a spectrophotometric assay. Parametric statistical analysis included Student's t-tests and linear regression while non-parametric analysis was undertaken using Fisher's exact test. Animals receiving BPD alone demonstrated tumour-to-tissue levels of approximately 2:1 while animals receiving the tumour-specific anti-EGFr-BPD conjugate had significantly better tumour:tissue ratios of 26:1 (P < 0.005). Animals treated with photofrin II had a 1 month cancer-free survival of 27% while animals treated with BPD had an improved survival of 67% (P = 0.03). The group treated with the tumour-specific anti-EGFr-BPD conjugate at a twentieth the total dose of BPD had an 80% 1 month cancer-free survival which was not statistically different from the group treated with BPD alone. Benzoporphyrin appears to be a more effective photosensitizing agent than Photofrin II and its tumour selectivity can be improved using a tumour specific monoclonal antibody conjugate.

Animals↗
PubMed1992

Inactivation of bovine herpesvirus-1 and bovine viral diarrhea virus in association with preimplantation bovine embryos using photosensitive agents.

Hematoporphyrin (HP), hematoporphyrin derivative (HPD), and thiopyronine (TP) are photosensitive agents (PSA) that have a germicidal effect when they are activated by light: helium neon laser (He/Ne) light (HP, HPD), white light (HP, HPD), and yellow-green light (TP). Experiments were conducted with appropriate controls to determine the effect of photosensitive agents a) for inactivating bovine herpesvirus-1 (BHV-1; titre 10(6) TCID50/ml) and bovine viral diarrhea virus (BVDV; titre 10(6) TCID50/ml); b) for disinfecting Day-7, zona pellucida-intact (ZP-I) bovine embryos that had been exposed to BHV-1 (titre 10(6) TCID50/ml) or BVDV (titre 10(6) TCID50/ml); and c) on the in vitro development of embryos. Exposure to HP, HPD and TP followed by light irradiation inactivated BHV-1 and BVDV. Embryos exposed to BHV-I were disinfected by HP or HPD (5 microg/ml) in combination with He Ne light, or by HP or HPD (10 microg/ml) in combination with white light. Embryos exposed to BVDV were disinfected by HPD (5 and 10 microg/ml) followed by He Ne or white light irradiation. Exposure of embryos to light alone or to light and HP or HPD had no detrimental effect on their in vitro development; however, exposure of embryos to TP (5 microg/ml) followed by irradiation caused embryonic degeneration. Exposure of embryos to 5 microg of HPD followed by He Ne light, or 10 microg/ml of HP or HPD, followed by white light, is simple methods of disinfecting them of BHV-I and BVDV.

Journal Article↗
PubMed1993

Pitfalls in evaluation of photosensitizing agents: an example with Q-switch II dye.

Photosensitizing agents potentiating laser therapy should have limited toxicity, no mutagenicity, stable spectral characteristics, and acceptable solubility when administered in vivo. Q-Switch II dye (QII) has been shown by others to be an effective chromophore for photodynamic therapy at 1051 nm in fibroblast cell culture. The objective of this study was to determine the spectral stability of QII in biological media and then to localize QII after administration in vivo. Spectral evaluation was performed between 250 and 1100 nm. QII dissolved in dimethyl sulfoxide (DMSO) rapidly lost its spectral characteristics, including its 1051-nm peak, when contacting water, minimal essential medium, human serum, organ surfaces, and intracellular fluid. One minute following intramuscular (IM) injection of 0.1 mg QII in 0.2 mL of DMSO, the dose precipitated as a discrete mass which was excised and reconstituted in DMSO. A new spectral pattern was seen, with no absorption between 850 and 1100 nm. Following intravenous (i.v.), (IM), or intraperitoneal (IP) injection, QII was not detected in any organ. Q-Switch II dye is not a suitable chromophore for in vivo photodynamic therapy at 1051 nm. Previous cell culture reports to the contrary did not account for the QII spectral change caused by biological media. Simple rapid assays are described to avoid this pitfall.

Absorption↗
PubMed1992

Skin photosensitizing agents and the role of reactive oxygen species in photoaging.

In this paper, the role of reactive oxygen species in photoaging is presented. Many photosensitizing agents are known to generate reactive oxygen species (singlet oxygen (1O2), superoxide anion (O2.-) and .OH radicals). Although photoaging (dermatoheliosis) of human skin is caused by UVB and UVA radiation, the hypothesis tested here in the pathogenesis of photoaging of human skin is the free radical theory involving the generation of reactive oxygen species by UVA (320-400 nm) radiation and their damaging oxidative effects on cutaneous collagen and other model proteins. The UVA-generated reactive oxygen species cause cross-linking of proteins (e.g. collagen), oxidation of sulfydryl groups causing disulfide cross-links, oxidative inactivation of certain enzymes causing functional impairment of cells (fibroblasts, keratinocytes, melanocytes, Langerhans cells) and liberation of proteases, collagenase and elastase. The skin-damaging effects of UVA appear to result from type II, oxygen-mediated photodynamic reactions in which UVA or near-UV radiation in the presence of certain photosensitizing chromophores (e.g., riboflavin, porphyrins, nicotinamide adenine dinucleotide phosphate (NADPH), etc.) leads to the formation of reactive oxygen species (1O2, O2.-, .OH). Four specific observations are presented to illustrate the concept: (1) the production of 1O2 and O2.- by UVB, UVA and UVA plus photosensitizing agents (such as riboflavin, porphyrin and 3-carbethoxypsoralens) as a function of UV exposure dose, the sensitizer concentration and the pH of the irradiated solution; (2) the formation of protein cross-links in collagen, catalase and superoxide dismutase by 1O2 and O2.- (.OH) and the resulting denaturation of proteins and enzyme activities as a function of UVA exposure dose; (3) the protective role of selective quenchers of 1O2 and O2.- (e.g. alpha-tocopherol acetate, beta-carotene, sodium azide, ascorbic acid, etc.) against the photoinactivation of enzymes and the prevention of the protein cross-linking reaction; (4) the possible usefulness of certain antioxidants or quenchers that interact with the UVA-induced generation of reactive oxygen species in the amelioration of the process of photoaging.

Animals↗
PubMed1994

Impaired accumulation of a cationic photosensitizing agent by a cell line exhibiting multidrug resistance.

Transport and accumulation of copper benzochlorin iminium salt (CDS1), a cationic photosensitizing agent, were examined using the P388/ADR murine leukemia, which exhibits the MDR (multidrug resistance) phenotype, and the wild-type parent cell line, P388. The recent availability of radioactive CDS1 permitted kinetic studies at drug levels in the submicromolar range. Exclusion of CDS1 by P388/ADR cells could be demonstrated, indicating that this agent is a substrate for the outward transport system associated with MDR. These results have implications with regard to the efficacy of cationic photosensitizers against this common neoplastic phenotype. The CDS1 was readily accumulated by P388 cells and by P388/ADR cells when the outward transport system was inhibited. Under these conditions, CDS1 was tightly bound and could not be washed out even when the outward transport system was reactivated.

Animals↗
PubMed1992

Experimental studies of immunotoxicity of a photosensitizing agent (Photofrin II) in mice.

Immunotoxicity studies have been performed on the photosensitizing agent Photofrin II (PHFR), a porphyrin derivative used in photodynamic therapy. Hybrid CD2F1 (H-2d/H-2d) or inbred C57Bl/6 (H-2b) male mice were injected with graded doses of the agent (from 1.2 to 12 mg/Kg ip) on day -5, -3 and -1 before assays. The animals, or spleen cells collected from them on day 0 with respect to PHFR treatment, were tested for: a) competence of producing GVHD upon cell transfer into allogeneic, immunosuppressed recipients; b) graft response against challenge with allogeneic lymphoma cells; c) delayed-type hypersensitivity (DTH) against sheep red blood cells; d) in vitro response to mitogens; e) NK cell activity; f) in vitro generation of alloreactive cytotoxic T lymphocytes (CTL); g) resistance against the challenge of a sublethal dose of Pseudomonas aeruginosa. Moreover the LD50 of the drug given ip has been determined in male CD2F1 mice. The results show that PHFR, even at the highest doses used, does not affect most of the immunological parameters studied, except for a marginal inhibition of CTL generation and increment in proliferative responses to Con A or LPS. These data along with parallel studies performed by our group on human models in vitro, showing increased susceptibility of PHFR-treated tumors to NK or LAK effector cells, point out that PHFR, in the absence of systemic photoactivation, is essentially non-immunotoxic in vivo and could render tumor cells more susceptible to natural immunity.

Animals↗
PubMed1993

Spectroscopic studies of cutaneous photosensitizing agents. XVIII. Indomethacin.

The photochemistry, photophysics, and photosensitization (Type I and II) of indomethacin (IN) (N-[p-chlorobenzoyl]-5-methoxy-2-methylindole-3-acetic acid) has been studied in a variety of solvents using NMR, high performance liquid chromatography-mass spectroscopy, transient spectroscopy, electron paramagnetic resonance in conjunction with the spin trapping technique, and the direct detection of singlet molecular oxygen (1O2) luminescence. Photodecomposition of IN (lambda ex > 330 nm) in degassed or air-saturated benzene proceeds rapidly to yield a major (2; N-[p-chlorobenzyl]-5-methoxy-2-methyl-3-methylene-indoline) and a minor (3; N-[p-chlorobenzoyl]-5-methoxy-2,3-dimethyl-indole) decarboxylated product and a minor indoline (5; 1-en-5-methoxy-2-methyl-3- methylene-indoline), which is formed by loss of the p-chlorobenzoyl moiety. In air-saturated solvents two minor oxidized products 4 (N-[p-chlorobenzoyl]-5-methoxy-2-methyl-indole-3-aldehyde) and 6 (5-methoxy-2-methyl-indole-3-aldehyde) are also formed. When photolysis was carried out in 18O2-saturated benzene, the oxidized products 4 and 6 contained 18O, indicating that oxidation was mediated by dissolved oxygen in the solvent. In more polar solvents such as acetonitrile or ethanol, photodecomposition is extremely slow and inefficient. Phosphorescence of IN at 77 K shows strong solvent dependence and its emission is greatly reduced as polarity of solvent is increased. Flash excitation of In in degassed ethanol or acetonitrile products no transients. A weak transient is observed at 375 nm in degassed benzene, which is not quenched by oxygen.(ABSTRACT TRUNCATED AT 250 WORDS)

Free Radicals↗
PubMed1998

Eradication of Acinetobacter baumannii by photosensitized agents in vitro.

The photodynamic effects of photosensitizers on Acinetobacter baumannii were studied. These Gram negative bacteria have recently been implicated in various infections, mainly acquired in hospitals. They have outstanding characteristics of multidrug high resistance to antimicrobial agents. The best photodynamic effect was obtained when A. baumannii cultures were treated with light activated deuteroporphyrin (Dp) at a concentration of 34 mumoles l-off and polymyxin nonapeptide (PMNP) at a concentration of 200 mumoles l-1. At these concentrations the culture in brain heart infusion (BHI) broth was found to be sterile after l h of treatment. Some inhibition was also obtained under the same conditions with Cd-texaphyrin (Cd-Tx) in the presence of PMNP. Treatment with various other photosensitizers in the presence of PMNP exhibited only marginal antibacterial activity. The cationic photosensitizer tetra-methylpyridyl porphine (TMPyP) did not exhibit any photodynamic effect on A. baumannii when illuminated during its growth in BHI broth. Bacteria grown in nutrient broth or suspended in saline and treated by TMPyP resulted in a significant photoinactivation by the sensitizer alone even in the absence of PMNP. It was found that a high concentration of the proteins present in BHI or in serum prevent TMPyP from acting as a photosensitizer against A. baumannii. Bovine serum albumin at the same high protein concentration prevents Dp (in the presence of PMNP) to act as a photosensitizer. The anionic photosensitizer tetra-sulfonatophenyl porphine (TPPS4) did not show any photodynamic effect in high or low protein media. In this study it was found that despite the high resistance of the Acinetobacter baumannii to antibiotics, these bacteria can be significantly photoinactivated by treatment with either Dp + PMNP or TMPyP in low protein content environments. When the protein concentration is high photoinactivation efficiency depends on the type of protein present in the medium.

Acinetobacter↗
PubMed1993

[Anthracycline derivatives as photosensitizing agents in photodynamic laser therapy: an in vitro study with squamous epithelial cancer cells of the mouth cavity].

Photodynamic laser therapy performed with hematoporphyrin derivatives has become increasingly important in the treatment of well-defined tumors in superficial sites. Limitations of this procedure result from the side effects of hematoporphyrin derivatives. In searching for possible alternatives to the usual photosensitizing agents, we studied the cytostatic drugs adriamycin and epirubicin. In order to evaluate the photodynamic effects of these agents we conducted in vitro studies on isolated cells from a squamous cell carcinoma of the oral cavity. The light source employed was an argon laser with wavelengths at 488/514 nm. Comparison of the cytostatic effect achieved by these anthracycline derivatives with and without laser light treatment showed a pronounced photodynamic effect. These results may herald new photodynamic therapeutic modalities.

Antibiotics, Antineoplastic↗
PubMed1978

Identification of topical photosensitizing agents in humans.

A method is described for the detection of topical photosensitizers in humans. Test agents were applied to the untanned midback under an occlusive dressing for 6 hr and then exposed to broad-spectrum radiation containing UV-A and visible wavelengths from a Xenon arc source. Well-known topical photosensitizers were readily identified. It was found that with certain poorly-penetrating substances, such as water-soluble dyes, applications to scarified skin were necessary to reveal phototoxic activity. In addition, these dyes were activated by wavelengths in the visible region of the spectrum.

Administration, Topical↗
PubMed1992

Pyrene butanol--an efficient, selective and non-metabolized photosensitizing agent for human myeloid leukemia cells.

Methods for ex vivo purging of neoplastic cells from harvested marrow are being developed to increase the efficacy of autologous transplantation. One approach is selective photosensitization, using sensitizing compounds and light radiation. Pyrene-containing fatty acids and lipids are potent photosensitizers, e.g. 12-(1-pyrene)dodecanoic acid (P12), is taken up preferentially by leukemic cells and undergo photoexcitation when exposed to long wave ultra-violet light, resulting in selective killing of leukemic cells. These compounds are incorporated into the neutral- and phospho-lipids of the cells. The presence of intracellular pyrene-linked lipids might present a potential hazard in applying these agents for clinical use. We have, therefore, studied a series of other pyrene-linked compounds with the objective of finding a non-metabolizable photosensitizing agent that can be easily removed from the cells. In the present paper we report the results with pyrene butanol (P4-OH), a pyrene linked short-chain alcohol. When compared to P12, P4-OH was found to be taken up by cells most rapidly and reached saturation within minutes. It did not undergo any metabolism and washing the cells with serum-containing salt solutions removed practically all the P4-OH. This compound was found to be an efficient photosensitizer (in terms of concentrations and time of incubation with the cells) and selective to leukemic cells--it caused a 99% reduction in leukemic clonogenic cells under conditions that normal hemopoietic progenitors remained almost intact. These properties make P4-OH a potential photosensitizer for clinical application.

Acute Disease↗