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C Abels

Publications and source records attributed to C Abels.

47 records · Page 3Linked to original sources
PubMed1995

[Use of photodynamic laser therapy in gynecology].

OBJECTIVE: Dysplasia of the vulva and uterine cervix are often multicentric, tend to recur and have mostly to be treated by surgical procedures. The photodynamic laser therapy (PDT) may be an alternative, which selectively destroys neoplastic tissue after topical delta-aminolevulinic acid (ALA) used as a photosensitizer. METHODS: We measured the distribution of fluorescence in dysplastic and nondysplastic tissue after topical application of ALA in 27 patients with dysplasia. In 3 vulvar and 2 cervical dysplasias, PDT was performed. RESULTS: We could show a selective enrichment of endogenous porphyrins in dysplastic tissues, whereas benign tissue showed no fluorescence. The fluorescence was limited to the mucosa. The heterogeneous fluorescence pattern was influenced by the duration of ALA application. In the treated patients, cytological and clinical parameters showed improvement after use of PDT. The longest recurrence-free interval from treatment up to date is 15 months (range 3-15 months). CONCLUSIONS: After first results of penetration studies and clinical follow-up, PDT after topical ALA application seems to be a good alternative to surgical procedures in dysplastic changes of the genital tract.

Adult↗
PubMed1994

Leukocyte/endothelial interactions and blood-brain barrier permeability in rats during cerebral superfusion with LTB4.

The experimental study analyses the vasomotor response (change of diameter of pial arterioles and venules), and blood-brain barrier function of the pia-arachnoidea at the rat brain surface before, during and after cerebral superfusion with 1.5 or 15.0 nM LTB4 in mock CSF. Leukocyte dynamics were studied by assessment of their centerline velocity, of rolling along ("roller") and attachment to ("sticker") the venular wall of white blood cells intravitally stained by Rhodamin 6G. Superfusion of the brain with LTB4 at both dose levels led to dilation of arterioles to 130% (p < 0.001), while of venules to 117% (p < 0.001) of control. The centerline velocity of leukocytes increased from 0.7 to 0.9 mm/s, however, only after superfusion with LTB4 at the high dose level. LTB4 induced a dose-dependent rolling (p < 0.01) and sticking of leukocytes (p < 0.001). Yet, a delay of about 60 min between cerebral administration of LTB4 and the maximal response of leukocyte rolling and sticking was observed. Whereas the blood-brain barrier was not opened by cerebral superfusion with 1.5 or 15.0 nM LTB4, for i.v. Na(+)-fluorescein, barrier leakage was promptly induced by 30.0 nM. The present findings demonstrate that cerebral administration of LTB4 by superfusion of the exposed brain surface is eliciting a pronounced vasomotor response, whereas the induction of leukocyte/endothelial interactions is less impressive.

Animals↗
PubMed1994

In vivo kinetics and spectra of 5-aminolaevulinic acid-induced fluorescence in an amelanotic melanoma of the hamster.

For successful photodynamic diagnosis (PDD) and effective photodynamic therapy (PDT) with the clinically used 'photosensitiser' 5-aminolaevulinic acid (ALA), knowledge of the maximal fluorescence intensity and of the maximal tumour-host tissue fluorescence ratio following systemic or local application is required. Therefore, time course and type of porphyrin accumulation were investigated in neoplastic and surrounding host tissue by measuring the kinetics and spectra of ALA-induced fluorescence in vivo. Experiments were performed in the amelanotic melanoma A-Mel-3 grown in the dorsal skinfold chamber preparation of Syrian golden hamsters. The kinetics of fluorescent porphyrins was quantified up to 24 h after i.v. injection of 100 mg kg-1, 500 mg kg-1 or 1,000 mg kg-1 body weight ALA by intravital fluorescence microscopy and digital image analysis (n = 18). In separate experiments fluorescence spectra were obtained for each dose by a simultaneous optical multichannel analysing device (n = 3). A three-compartment model was developed to simulate fluorescence kinetics in tumours. Maximal fluorescence intensity (per cent of reference standard; mean +/- s.e.) in the tumour arose 150 min post injection (p.i.) (1,000 mg kg-1, 109 +/- 34%; 500 mg kg-1, 148 +/- 36%) and 120 min p.i. (100 mg kg-1, 16 +/- 8%). The fluorescence in the surrounding host tissue was far less and reached its maximum at 240 min (100 mg kg-1, 6 +/- 3%) and 360 min p.i. (500 mg kg-1, 50 +/- 8%) and (1,000 mg kg-1, 6 +/- 19%). Maximal tumour-host tissue ratio (90:1) was encountered at 90 min after injection of 500 mg kg-1. The spectra of tissue fluorescence showed maxima at 637 nm and 704 nm respectively. After 300 min (host tissue) and 360 min (tumour tissue) additional emission bands at 618 nm and 678 nm were detected. These bands indicate the presence of protoporphyrin IX (PPIX) and of another porphyrin species in the tumour not identified yet. Tumour selectivity of ALA-induced PPIX accumulation occurs only during a distinct interval depending on the administered dose. Based on the presented data the optimal time for PDD and PDT in this model following intravenous administration of 500 mg kg-1 ALA would be around 90 min and 150 min respectively. The transient selectivity is probably caused by an earlier and higher uptake of ALA in the neoplastic tissue most likely as a result of increased vascular permeability of tumours as supported by the mathematical model.

Aminolevulinic Acid↗
PubMed1990

Effect of stimulation of leukocyte chemotaxis by fMLP on white blood cell behaviour in the microcirculation of rat brain.

The role of white blood cells in acute cerebral disorders such as ischemia or stroke is still unclear. Therefore, in the present study we investigated the effects of the leukotaxin n-formyl-methionyl-leucyl-phenylalanine (fMLP) on white blood cell endothelial-cell interactions in the rat brain surface microcirculation. An improved closed cranial window technique was applied. Superfusion of fMLP in rising concentrations (10(-8) - 10(-5) M) was seen to induce rolling and adherence of leukocytes to teh endothelium of small venules. Rolling was more effectively stimulated than firm attachment. fMLP-induced vasodilation was more pronounced in arterioles than in venules. In this study it has been shown that the hydrophilic fMLP is effectively stimulating neutrophil chemotaxis across the blood-brain barrier. Further, the closed cranial window preparation is useful to analyze quantitatively properties of activated leukocytes, which may be pertinent in injury to the blood-brain barrier and induction of microcirculatory disturbances.

Animals↗
PubMedDate not supplied

Topical photodynamic therapy for localized scleroderma.

Therapy of localized scleroderma is unsatisfactory, with numerous treatments being used that have only limited success or considerable side-effects. The aim of this trial was to determine whether topical photodynamic therapy would be effective in patients with localized scleroderma. Five patients with progressive disease, in whom conventional therapies had failed, were treated by application of a gel containing 3% 5-aminolevulinic acid followed by irradiation with an incoherent lamp (40 mW/cm2, 10 J/cm2). The treatment was performed once or twice weekly for 3-6 months. In all patients the therapy was highly effective for sclerotic plaques, as measured by a quantitative durometer score and a clinical skin score. The only side-effect was a transient hyperpigmentation of the treated lesions. These cases document the beneficial effect of topical photodynamic therapy in localized scleroderma. Controlled trials are now necessary to confirm these preliminary results.

Adult↗
PubMedDate not supplied

Photosensitization of skin-derived cell lines by Dimegin [2,4-di-(alpha-methoxyethyl)-deuteroporphyrin IX] in vitro.

The deuteroporphyrin-IX derivative Dimegin [2,4-di-(alpha-methoxyethyl)-deuteroporphyrin IX] was investigated with respect to cellular uptake, intracellular localization and cell survival 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 determined the cellular fluorescence as a marker of the uptake of Dimegin after incubation for 24 h. The intracellular localization of Dimegin was analysed using fluorescence microscopy and co-staining with fluorescent dyes specific for cell organelles. Following irradiation with an incoherent light source (580-740 nm) using a light dose of 24 J/cm2, phototoxicity was determined by means of trypan blue dye exclusion, MTT assays and growth curves. The relative Dimegin fluorescence of the different cell lines declined as follows: SCL1 > HaCaT > N1 > SCL2. Intracellular localization of Dimegin was found in the mitochondria. For all cell lines Dimegin concentrations above 15 microM yielded a significant phototoxic effect. The EC50 for SCL1 cells was 8.9 +/- 2.0 microM Dimegin. The EC50 for the cell lines increased as follows: SCL1 < HaCaT < N1 < SCL2, thus correlating with the cellular fluorescence of Dimegin. The results of the MTT assay were confirmed by trypan blue dye exclusion assay and growth curves. In conclusion, the study shows that Dimegin is an effective photosensitizer with a rapid mechanism of action in vitro, resulting in an immediate loss of plasma membrane integrity following irradiation.

Carcinoma, Squamous Cell↗
PubMedDate not supplied

Measurement of neutrophil content in brain and lung tissue by a modified myeloperoxidase assay.

Myeloperoxidase (MPO) activity is assessed for the quantification of neutrophil accumulation in tissues. In particular, it may be used to support in vivo data on leukocyte kinetics obtained by intravital microscopy and to clarify whether phenomena observed on the organ surface reflect the situation of the whole organ microcirculation. Previous measurements of MPO activity were limited by interference with other peroxidases and by inhibition of MPO activity by specific enzymes. To circumvent these limitations, a modified assay was devised that combined a two-step tissue homogenization technique with heat incubation in a continuous photometric measurement. MPO activity was quantified in neutrophils isolated from rat and rabbit whole blood, rat brain and rabbit lung and compared with intravital microscopic data on leukocyte accumulation. The modified assay is characterized by high reproducibility, strong correlation of MPO activity with number of neutrophils and full recovery of neutrophils added to tissue homogenate. MPO activity per neutrophil was 342.9 +/- 11.7 mU/10(6) cells in rats and 40.3 +/- 0.8 mU/10(6) cells in rabbits. MPO activity in tissue was significantly lower in rat brains (18.9 +/- 29.7 mU/g) as compared to rabbit lungs (741 +/- 67 mU/g). Whereas global cerebral ischemia/reperfusion did not increase MPO activity in rat brain (18.1 +/- 26.1 mU/g), intravenous infusion of cobra venom factor (1,447 +/- 407 mU/g) or endotoxin (1,439 +/- 285 mU/g), enhanced MPO activity in rabbit lung. These results parallel microcirculatory data from the organ surface. Therefore they supplement the intravital microscopic observations by demonstrating that these are indeed representative of deeper parenchymal tissue areas.

Animals↗