Biomedical subjects

C Abels

Publications and source records attributed to C Abels.

At least 19 recordsLinked to original sources

PubMed2006

[Therapy of atopic dermatitis].

Atopic eczema is one of the most common diseases in dermatology. Patients suffer from both the chronic relapsing skin disease and the associated emotional stress. Itching and visible lesions on the face and hands are the most unpleasant features for many often young patients, seriously reducing their quality of life. New therapeutic approaches have changed the management of atopic eczema in recent years. Relatively potent new drugs with fewer side effects than corticosteroids help to control the disease. This review focuses on the basic principles of modern atopic eczema treatment, emphasizing basic emollient therapy and topical therapy with calcineurin inhibitors.

Adolescent↗

PubMed2005

[Antibacterial photodynamic therapy. A new treatment for superficial bacterial infections?].

The basis of "antibacterial photodynamic therapy" involves the killing of bacteria by reactive oxygen species in the presence of a photosensitizer and light. Possible dermatologic indications include inactivation of bacteria in skin and wound infections and reduction in density of nosocomial multi-resistant infections. The chief advantage of antibacterial photodynamic therapy is that regardless of the resistance pattern of a bacteria, inactivation can be achieved, analogous to the use of antiseptics. The aim of the present review is to describe the physicochemical and biological mechanisms of antibacterial photodynamic therapy as well as possible clinical indications in dermatology.

Anti-Bacterial Agents↗

PubMed2005

Photodynamic effects of novel XF porphyrin derivatives on prokaryotic and eukaryotic cells.

The worldwide rise in the rates of antibiotic resistance of bacteria underlines the need for alternative antibacterial agents. A promising approach to the killing of gram-positive antibiotic-resistant bacteria of the skin uses light in combination with a photosensitizer to induce a phototoxic reaction. Different concentrations (0 to 100 microM) of porphyrin-based photosensitizers (CTP1, XF70, and XF73) and different incubation times (5 min, 1 h, and 4 h) were used to determine phototoxicity against two methicillin-resistant Staphylococcus aureus strains, one methicillin-sensitive S. aureus strain, one methicillin-resistant Staphylococcus epidermidis strain, one Escherichia coli strain, and human keratinocytes and fibroblasts. Incubation with 0.005 microM XF70 or XF73, followed by illumination, yielded a 3-log10 (> or = 99.9%) decrease in the viable cell numbers of all staphylococcal strains, indicating that the XF drugs have high degrees of potency against gram-positive bacteria and also that the activities of these novel drugs are independent of the antibiotic resistance pattern of the staphylococci examined. CTP1 was less potent against the staphylococci under the same conditions. At 0.005 microM, XF70 and XF73 demonstrated no toxicity toward fibroblasts or keratinocytes. No inactivation of E. coli was detected at this concentration. XF73 was confirmed to act via a reactive oxygen species from the results of studies with sodium azide (a quencher of singlet oxygen), which reduced the killing of both eukaryotic and prokaryotic cells. When a quencher of superoxide anion and the hydroxyl radical was used, cell killing was not inhibited. These results demonstrate that the porphyrin-based photosensitizers had concentration-dependent differences in their efficacies of killing of methicillin-resistant staphylococcal strains via reactive oxygen species without harming eukaryotic cells at the same concentrations.

Anti-Bacterial Agents↗

PubMed2004

Structure-activity relationships of three differently substituted 2,7,12,17-tetrakis-(beta-methoxyethyl) porphycene derivatives in vitro.

The subcellular localization, efficacy and photooxidative mechanism of three new photosensitizing porphycenes (HexoTMPn, PeloTMPn, CpoTMPn) for photodynamic therapy with different substituents at position 9 of the tetrapyrrole macrocycle were investigated in vitro using different human skin-derived cell lines (HaCaT, SCL I, SCL II) with the aim of customizing the side-chain chemistry to accelerate cellular uptake and so enhance photodynamic activity. Cells were incubated with a porphycene and costained with organelle-specific markers. Subcellular localization was determined by fluorescence microscopy. Also, cells were incubated with different sensitizer concentrations (0-1000 nmol/l) and irradiated by an incoherent light source (lambda(em) = 600-750 nm, 40 mW/cm(2), 24 J/cm(2)) with/without quenchers or enhancers (NaN(3), histidine, mannitol or D(2)O). Cell viability was assessed. All porphycenes were localized in perinuclear lysosomes and induced a decrease in mitochondrial activity following irradiation. HexoTMPn was the most efficient in all three cell lines (EC(50) in HaCaT cells: HexoTMPn 14 nmol/l, CpoTMPn 62 nmol/l, PeloTMPn 89 nmol/l). Addition of either NaN(3) or histidine reduced the phototoxicity significantly. Due to the short lifetime of singlet oxygen, the sites of sensitizer localization are the initial subcellular targets. The cytotoxicity of each sensitizer varied depending on singlet oxygen quantum yield and cell line. Despite the different chemical structures, the biological effects were not very distinct, since they seemed to be mostly determined by the tetrapyrrole ring and only slightly modified by the substituent at position 9. Also, there was only a narrow margin between biological compatibility and efficacy.

Cell Line↗

PubMed2003

Effects of light fractionation and different fluence rates on photodynamic therapy with 5-aminolaevulinic acid in vivo.

To improve efficacy of photodynamic therapy (PDT) with intravenously administered 5-aminolaevulinic acid (ALA) fractionating the light dose or reducing the light intensity may be a possibility. Therefore, Syrian Golden hamsters were fitted with dorsal skinfold chambers containing an amelanotic melanoma (n=26). PDT was performed (100 mW cm(-2), 100 J cm(-2), continuously or fractionated, and 25 mW cm(-2), 100 J cm(-2); continuously or fractionated) using an incoherent light source following i.v. application of ALA. Following fractionated irradiation, the light was paused after 20 J cm(-2) for 15 min. Prior to and up to 24 h after PDT tissue, pO(2) was measured using luminescence lifetime imaging. The efficacy was evaluated by measuring the tumour volume of amelanotic melanoma cells grown subcutaneously in the back of Syrian Golden hamsters (n=36). Only high-dose PDT resulted in a significant decrease of pO(2). Irrespective of the mode of irradiation only high-dose PDT induced complete remission of all tumours (13 out of 13). It could be shown that low-dose PDT failed to induce a significant decrease of pO(2). No significant effect of fractionated irradiation was shown regarding the therapeutic efficacy 28 days after PDT. Thus performing a fractionated PDT with ALA or reducing the light intensity seems not to be successful in clinical PDT according to the present data.

Aminolevulinic Acid↗

PubMed2003

Histopathological diagnosis of onychomycosis by periodic acid-Schiff-stained nail clippings.

BACKGROUND: The current laboratory methods for diagnosing fungal infections of the nails are the potassium hydroxide (KOH) scraping technique and fungal culture. However, due to the long incubation period required for fungal culture and the reported rate of approximately 30% false negative results observed when using these methods, a quick and highly specific screening test for diagnosing onychomycosis is urgently needed. OBJECTIVES: In a prospective study, to compare the traditional mycological diagnostics using culture medium and KOH preparation with the histopathological diagnosis of onychomycosis by periodic acid-Schiff (PAS)-stained nail clippings. METHODS: Material from 387 nails of 350 patients suspected of having onychomycosis was obtained and a KOH stain as well as two fungal cultures (Kimmig agar with and without cycloheximide) were prepared. In addition, the same specimen was histopathologically examined (PAS stain). RESULTS: Culture medium and KOH preparation respectively revealed 100 and 156 cases of onychomycosis, as compared with 182 cases by histological examination. Histological examination gave a significantly higher rate of positive results (P < 0.05). Considering the total number of positive results given by at least one of the three methods (total = 438), histological evaluation was found to give the highest rate of successful recognition of mycotic infection (41.6%). CONCLUSIONS: The histopathological evaluation of PAS-stained nail clippings is very quick and easy to perform, and will increase the frequency of diagnosing onychomycotic disease above that achieved by culture and KOH preparation alone. However, because information concerning the vitality of the fungi and accurate identification of the specific pathogen is not available through this investigation alone, mycological culture continues to remain the indisputable 'gold standard' of mycological diagnostics.

Adolescent↗

PubMed2002

[Cutaneous microdialysis. Use in dermatology].

The determination of concentrations of exogenous or endogenous substances in the dermis, e.g. for pharmacokinetic studies, is technically difficult. Performing skin biopsies or inducing suction blisters results in the disintegration of the tissue and allows only single measurements. Recently, cutaneous microdialysis, a new simple and minimally invasive technique for continuously measuring of substances in the dermis in vivo, has been introduced in dermatological research. According to the principle of dialysis, a semipermeable membrane is inserted in the dermis and due to a concentration gradient between the interstitial space and a perfusate, substances diffuse through the pores of the membrane and can be analyzed in the dialysate. Cutaneous microdialysis represents a useful technique for pharmacokinetic or pharmacodynamic studies as well as for investigations regarding cutaneous physiology and pathophysiology.

Biological Availability↗

PubMed2001

[Photochemotherapy of cutaneous AIDS-associated Kaposi sarcoma with indocyanine green and laser light].

BACKGROUND AND OBJECTIVE: Indocyanine green (ICG) is a clinically approved dye for diagnostic purposes, which has an absorption peak in the near infrared and remains intravascular due to a high plasma protein binding. Its therapeutic potential in combination with a diode laser was studied for well vascularized cutaneous tumors. PATIENTS/METHODS: Six male patients (mean age 49.2 years) with AIDS-related Kaposi sarcomas (n = 30) received ICG (2 x 2 mg/kg i.v.) followed directly by irradiation with a diode laser (lambda = 805 nm, 100 J/cm2, 3 W/cm2). RESULTS: All macular and plaque-type lesions (n = 27) showed primarily blister- and crust formation and healed within 14 days. Only one out of the 3 nodular lesions treated showed complete remission. The only side effect recognized was a mild burning sensation during irradiation. Nineteen lesions resolved completely leaving a slight atrophic scar, in three lesions a transient postinflammatory hyperpigmentation occurred. Within the follow-up period of 2 years no recurrence was detected. CONCLUSIONS: The ICG-mediated photochemotherapy is an effective palliative therapeutic modality with a low rate of side effects in the treatment of macular or plaque-type cutaneous Kaposi sarcomas.

Acquired Immunodeficiency Syndrome↗

PubMed2001

[Truss-induced macular amyloidosis].

A 80-year-old male presented with a long time history of a localized red-brown macule with superficial lichenification and slight scaling in the right groin. An earlier skin biopsy revealed the presence of amyloid deposits. The patient therefore had a complete internal checkup including a rectal biopsy for exclusion of systemic amyloidosis. However, the laboratory data did not reveal any specific abnormalities including immunoglobulins and Bence-Jones protein. The rectal biopsy was also nonspecific. After skin examination, a rebiopsy was performed at our department showing acanthosis and spongiosis of the epidermis with parakeratosis. A homogenous eosinophilic deposit was present in the upper dermis and stained positive with thioflavine. At the second visit the patient wore a truss for a right inguinal hernia, perfectly matching the area of the skin lesion. Thus, the diagnosis of a localized macular amyloidosis was confirmed very likely due to permanent local friction. The classification of localized cutaneous amyloidoses should include local trauma as a cause to avoid unnecessary and exhausting internal checkups to exclude systemic involvement.

Aged↗

PubMed2000

[Fluorescence-assisted biopsy of basal cell carcinomas].

BACKGROUND AND OBJECTIVE: The diagnosis of precancerous and cancerous skin lessons in pretreated or scarred skin can be difficult. The determination of the right biopsy site in a suspected area depends largely on the physician's experience. PATIENTS/METHODS: The possibility of using a CCD-camera system and measuring tumor fluorescence following topical application of 5-aminolevulinic acid was employed in a single case to facilitate accurate choice of biopsy site. RESULTS: An user-independent evaluation of the induced fluorescence intensity was achieved by means of the described optical system and digital imaging. The contrast of the acquired fluorescence images can be significantly enhanced and allows the determination of a threshold. As result an initial, clinically not visible basal cell carcinoma was detected and excised by a punch biopsy in toto. CONCLUSIONS: Using the described optical system the early recognition of a superficial basal cell carcinoma and the determination of the exact biopsy site was achieved in pretreated skin. The routine employment of the system will be assessed in a prospective study.

Administration, Topical↗

PubMed2000

Indocyanine green (ICG) and laser irradiation induce photooxidation.

The cellular uptake and subcellular localization of indocyanine green (ICG; absorption band 700-850 nm), and cell survival and ultrastructural changes following ICG-mediated phototherapy were investigated in vitro in four different cell lines derived from human skin (SCL1 and SCL2 squamous cell carcinoma, HaCaT keratinocytes and N1 fibroblasts). The cellular uptake of ICG (1-50 microM, incubation times 1, 4, 24 h) was saturable, highly cumulative and could be inhibited by the addition of 250 microM bromosulphophthalein indicating the involvement of the organic anion transporting polypeptide (OATP). For HaCaT cells, the maximum cellular uptake (Vmax) and the Michaelis constant (K(m)) were 9.9 +/- 1.1 mM and 47 +/- 16 microM, respectively, following a 24-h incubation with ICG. Fluorescence microscopy revealed a cytoplasmic distribution of ICG, probably bound to glutathione S-transferase. Following irradiation with a cw-diode laser (805 nm, 80 mW/cm2) at doses of 24 or 48 J/cm2, the phototoxicity was determined using the MTT assay as a measure of cell viability. For all cell lines, ICG concentrations above 25 microM produced a significant phototoxic effect. The EC50, of ICG for HaCaT cells following irradiation at 24 J/cm2 was 20.1 +/- 3.9 microM. Growth curves showed that even HaCaT cells treated at the EC50 were killed within a week following treatment. Electron microscopy 1 h after ICG-mediated phototherapy revealed cytoplasmic vesiculation, dilation of the rough endoplasmic reticulum, the Golgi complex and the perinuclear cisternae and the beginning of chromatin condensation in the nucleus. These ultrastructural findings are not consistent with a photothermal action of ICG-mediated phototherapy. Taken together with those of previous studies by our group these results support photooxidation as a major cell-killing mechanism.

Cell Line↗

PubMed2000

Characterization and prevention of phototoxic effects in intravital fluorescence microscopy in the hamster dorsal skinfold model.

Intravital microscopy is widely used to study the microcirculation. However, the use of fluorescent dyes can induce phototoxic effects which may affect the measurements, particularly in tissue exposed to oxidative stress. The aim of the study was to determine the threshold light dose at which fluorescent microscopy is associated with phototoxic effects in the hamster dorsal skinfold chamber under normal and pathological conditions. The extent of phototoxicity in the microcirculation in the hamster skinfold chamber was investigated using intravital fluorescent microscopy during 60 min of illumination (1048 mW/cm2) applying two different concentrations of fluorescein isothiocyanate dextran under baseline conditions (groups A and B) and following 4 h of ischemia (groups C and D). In the second part of the study the microvasculature was analyzed regarding phototoxic effects during a standardized intravital microscopic examination after 4 h of pressure induced ischemia. Groups I and II (n=7) were studied using epiillumination after injection of fluorescein isothiocyanate dextran plus rhodamine 6G or rhodamine 6G only. In group III (n=7) only transillumination was used. Arteriolar vasospasm, microvascular perfusion failure, thrombus formation, and enhanced leukocyte endothelium interaction were observed as signs of a phototoxic effect in normal tissue. However, the light doses needed to induce these effects clearly exceeded those during standard examinations. The induction of a 4-h ischemia and reperfusion further enhanced these effects. Despite the predamage by ischemia/reperfusion the comparison of epiillumination and transillumination microscopy using a standard protocol showed no differences regarding the parameters analyzed at any time. This indicates that epiillumination and the fluorescent dyes per se did not affect the experimental results. These results show that ischemia/reperfusion studies in the dorsal skinfold chamber of the Syrian golden hamster can be carried out safely without the risk of inducing phototoxic effects by fluorescent microscopy. Nevertheless every laboratory using epiillumination and fluorescent dyes should take precautions to avoid these effects by the use of sensitive cameras to lower the light dose.

Animals↗

PubMed2000

Leukocyte-endothelium-interaction in pial vessels following global, cerebral ischaemia.

BACKGROUND: Investigations have shown an increase of leukocyte-endothelium-interaction in a variety of organs following an ischaemic insult. To elucidate the role of leukocyte-endothelium-interaction following global, cerebral ischaemia the present study was performed. METHODS: Global, cerebral ischaemia was induced for twenty minutes by four-vessel-occlusion (PULSINELLI). Leukocyte-endothelium-interaction was studied in the cerebral microcirculation using a rat closed cranial window and intravital microscopy. Leukocytes were stained intravenously using rhodamine 6G. Diameters of pial vessels, leukocyte centreline velocity and number of rolling or adhering leukocytes were determined off-line up to 2 h following global cerebral ischaemia. To confirm these results immunohistochemistry of the brain was performed. FINDINGS: Four-vessel-occlusion induced an iso-electric EEG, venular stasis and minimal rest flow in arterioles. Reperfusion yielded a significant increase of the arteriolar (p < 0.001) and a smaller increase of the venular diameters (p < 0.01). Up to 2 h after ischaemia no significant increase of the number of rolling or adhering leukocytes was measured which was confirmed by immunohistochemistry. INTERPRETATION: In contrast to other studies, in particular regarding focal cerebral ischaemia, an increase of leukocyte-endothelium-interaction in rat brain following 20 min of global cerebral ischaemia was not observed despite histological evidence of ischaemic damage. Thus in our model leukocytes seem not to contribute to the brain damage following global ischaemia.

Animals↗

PubMed2000

Does smoking influence the efficacy of bath-PUVA therapy in chronic palmoplantar eczema?

Bath-PUVA therapy has been described as successful treatment for palmoplantar eczema. However, our own observations showed that patients with palmoplantar eczema of the dyshidrotic or hyperkeratotic type responded only partially to bath-PUVA therapy. In order to evaluate environmental influences possibly having an impact on the efficacy of this therapy, smokers and non-smokers suffering from palmoplantar eczema treated with bath-PUVA therapy were compared. A retrospective study was conducted involving 62 patients, 39 non-smokers and 23 smokers, with palmar and/or plantar eczema resistant to local corticosteroids. Bath-PUVA therapy was performed according to the European standard regimen for oral PUVA therapy. The total number of treatments and the cumulative UVA-dose were similar in smokers and non-smokers (smokers 24+/-17.7 (mean+/-SD) and 67.6+/-51.3 J/cm2 vs. non-smokers 25.7+/-16.3 and 68.5+/-49.3 J/cm2). In the group of non-smokers, 31% showed complete remission (CR; 100% clearance), 33% partial remission (PR; more than 50% clearance) and 36% no change after treatment (NC; less than 50% clearance). In contrast, the group of smokers showed only 13% CR and 22% PR, whereas 65% exhibited NC. The differences regarding complete or partial remission between the groups were statistically significant (Student t-test for paired samples; P<0.05). Regarding the different type of eczema, bath-PUVA proved to be more successful in the dyshidrotic type of eczema as compared to the hyperkeratotic type in non-smokers (P<0.05). In the group of smokers no CR was achieved in patients suffering from the dyshidrotic form of eczema. Smoking is likely to be a reason for the failure of bath-PUVA therapy in the treatment of chronic palmoplantar eczema, in particular regarding smokers with eczema of the dyshidrotic type where no complete remission was achieved.

Adult↗

PubMed2000

Overexpression of melanoma inhibitory activity (MIA) enhances extravasation and metastasis of A-mel 3 melanoma cells in vivo.

The secreted MIA protein is strongly expressed by advanced primary and metastatic melanomas but not in normal melanocytes. Previous studies have shown that MIA serum levels correlate with clinical tumour progression in melanoma patients. To provide direct evidence that MIA plays a role in metastasis of malignant melanomas, A-mel 3 hamster melanoma cells were transfected with sense- and antisense rhMIA cDNA and analysed subsequently for changes in their tumorigenic and metastatic potential. Enforced expression of MIA in A-mel 3 cells significantly increased their metastatic potential without affecting primary tumour growth, cell proliferation or apoptosis rate in hamsters, compared with control or antisense transfected cells. Additionally, MIA overexpressing transfectants showed a higher rate of both tumour cell invasion and extravasation. Cells transfected with MIA antisense generally exerted an opposite response. The above changes in function attributed to the expression of MIA may underlie the contribution of MIA to the malignant phenotype.

Animals↗

PubMed1999

Long-pulse dye laser for photodynamic therapy: investigations in vitro and in vivo.

BACKGROUND AND OBJECTIVE: Continuous wave lasers or incoherent lamps are used effectively for photodynamic therapy (PDT). As the mechanism of action of pulsed lasers in PDT is not known, we investigated the efficacy of PDT with 5-aminolevulinic acid (ALA) using a long-pulse (1.5 ms) tunable flashlamp-pumped pulsed dye laser (LPDL) in vitro and in vivo. STUDY DESIGN/MATERIALS AND METHODS: HaCaT human keratinocytes were incubated with ALA (3 mmol/l) and irradiated (0-50 J/cm(2)) using the LPDL at 585 nm, 595 nm, or 600 nm vs. an incoherent light source (580-740 nm). Topical ALA-PDT was performed on 24 patients with actinic keratoses (AK) on the head (n = 200) after incubation with a 20% ALA emulsion and irradiation by either an incoherent light source (160 mW/cm(2), 60-160 J/cm(2)) or the LPDL (585 nm, 18 J/cm(2)). RESULTS: Maximal cytotoxic effects in vitro were achieved using the LPDL at 585 nm or the incoherent lamp (50 J/cm(2)). Sodium azide, a quencher of singlet oxygen, significantly reduced cell killing, suggesting that the cytotoxic effects are mainly mediated by singlet oxygen. This is supported by an increase of lipid peroxides as determined by malondialdehyde after adding D(2)O. Complete remission was achieved in 79% of 100 AK treated by ALA and the LPDL and in 84% of 100 AK treated by ALA and the incoherent lamp. Pain during light treatment was significantly reduced by using the LPDL. Control lesions (LPDL without ALA) did not clear. CONCLUSION: These results show the in vitro and in vivo efficacy of ALA-PDT using a pulsed light source mediated by singlet oxygen.

Adolescent↗

PubMed1999

Photosensitization of human skin cell lines by ATMPn (9-acetoxy-2,7,12,17-tetrakis-(beta-methoxyethyl)-porphycene) in vitro: mechanism of action.

9-Acetoxy-2,7,12,17-tetrakis-(beta-methoxyethyl)-porphycene (ATMPn) is a promising new photosensitizer characterized by high absorption around 640 nm and high singlet oxygen yield. To study the mechanism of action in vitro we have investigated uptake, intracellular localization, cell survival and ultrastructural changes following photodynamic treatment in human cell lines derived from the skin (SCL1 and SCL2, squamous cell carcinoma; HaCaT keratinocytes; N1 fibroblasts). Using flow cytometry we have determined the cellular fluorescence as a marker for the uptake of ATMPn after incubation for 60 min. Co-staining with ATMPn and fluorescent dyes specific for cell organelles reveals an intracellular localization of ATMPn in lysosomes. Following irradiation using an incoherent light source (580-740 nm) and a light fluence of 24 J cm-2, phototoxicity is determined by means of the 3-4.5 dimethylthiazol-2,5 diphenyl tetrazolium bromide (MTT) assay. For all cell lines ATMPn concentrations above 15 nM yield a significant phototoxic effect. The 50% effective concentration, EC50, for SCL1 cells is 11.2 +/- 2.9 nM ATMPn. ATMPn uptake and phototoxicity are more effective for HaCaT and SCL1 as compared to SCL2 and N1 cells. Growth curves confirmed the results of the MTT assay. Because of the high lysosomal accumulation of ATMPn, already low photosensitizer concentrations without dark toxicity yield a high photodynamic effect. Immunofluorescence and electron microscopy reveal damage to tonofilaments, plasma membrane and mitochondria, indicating a mechanism unrelated to apoptosis. A dose yielding complete cell killing, as needed for oncological indications, might lead to necrosis, whereas lower sub-lethal doses result in induction of apoptosis.

Cell Line↗

PubMed1999

Photo-oxidative killing of human colonic cancer cells using indocyanine green and infrared light.

Despite of the approval of Photofrin in various countries, chemically defined sensitizers for photodynamic therapy (PDT) are still needed for the absorption of light in the infrared spectrum, which provides a maximal penetration of light into tissue. Therefore, both the efficacy and the mechanism of action of the clinically approved dye indocyanine green (ICG) and laser irradiation were investigated in vitro. For the investigation of phototoxic effects, HT-29 cells were incubated 24 h prior to irradiation by using different concentrations of ICG (10-500 microM). In each experiment, cells were irradiated using a continuous wave (cw)-diode laser (lambda(ex) = 805 nm, 30 J cm(-2), 40 mW cm(-2)). After laser irradiation, cell viability of dark control and of cells incubated with 500 microM ICG was 1.27+/-0.11 or 0.28+/-0.05 respectively. Using 100 microM ICG and D2O, cell viability was further decreased from 0.46+/-0.03 (H2O) to 0.11+/-0.01 (D2O). Using D2O and 100 microM ICG, the concentration of malondialdehyde, a marker of lipid peroxidation, increased from 0.89+/-0.10 nmol 10(-6) cells to 11.14+/-0.11 nmol 10(-6) cells. Using 100 microM ICG and laser irradiation sodium azide or histidine (50 mM), quenchers of singlet oxygen reduced the cell killing significantly. In contrast, when using mannitol, a quencher of superoxide anion and hydroxyl radical, cell killing was not inhibited. According to the present results, photoactivated ICG seems to kill colonic cancer cells due to the generation of singlet oxygen and the subsequent formation of lipid peroxides. Therefore, ICG might present a promising photosensitizer for PDT; first clinical results confirm these findings.

Cell Death↗