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J Moan

Publications and source records attributed to J Moan.

202 records · Page 12Linked to original sources
PubMedDate not supplied

Acid-base properties of chlorin e6: relation to cellular uptake.

Chlorins are attractive compounds for photodynamic therapy because of their high absorption in the red spectral region. In this study, the absorbance, fluorescence excitation and fluorescence emission spectra of chlorin e6 have been recorded as functions of pH in phosphate-buffered saline (PBS) solution with and without fetal calf serum (FCS). For pure PBS solutions, variation of the pH of the solution results in a shift of both the absorption and the fluorescence spectrum as well as in a decrease of the fluorescence intensity. Spectrophotometric and fluorimetric titration curves, based on observed changes, have been plotted. There is an indication of aggregate formation at low pH values (pH < 5). The presence of 5% FCS results in a shift of the titration curve, from an inflection point at about 6.5 to one at about 7.6. Pronounced spectral changes of the fluorescence emission spectra of protein-bound chlorin e6 (change of spectral shape, decrease of peak intensity) are also observed. The partition coefficients in the 1-octanol-water system increase with decreasing pH. Thus, relatively more of the drug is incorporated in the octanol phase at low pH. Cellular uptake of chlorin e6 in the presence of serum is significantly higher at pH 6.7 as compared with that at 7.3 and 7.6. We conclude that a change in the pH value of the surrounding medium leads to a change in the lipophilicity of chlorin e6. Such a change is likely to influence its binding to the serum proteins as well as its interaction with the plasma membrane of cells and may also be related to the selective tumor uptake of the drug.

Breast Neoplasms↗
PubMedDate not supplied

Correlation of subcellular and intratumoral photosensitizer localization with ultrastructural features after photodynamic therapy.

Photodynamic therapy (PDT) of cancer typically involves systemic administration of tumor-localizing photosensitizers followed 48-72 h later by exposure to light of appropriate wavelengths. Knowledge about the distribution of photosensitizers in tissues is still fragmentary. In particular, little is known as to the detailed localization patterns of photosensitizers in neoplastic and normal tissues as well as the relationship between such patterns and the actual targets for the photosensitizing effect. This review focuses on ultrastructural features seen in treated cells and tumors. An attempt is made to correlate these findings with the subcellular/intratumoral localization pattern of the photosensitizers in tumor cell lines in vitro and in tumor models in vivo. Several subcellular sites are main targets of PDT with different sulfonated aluminum phthalocyanines (AIPcSn) in the human tumor cell line LOX. Nuclei are not among the primary targets. Overall, the ultrastructural changes correlate well with the data about the subcellular localization patterns for each analogue of AIPcSn in the same cell line. Similar findings are also obtained for the family of sulfonated mesotetraphenylporphines (TPPSn) in the NHIK 3025 cell line. The mechanisms involved in the killing of tumors by PDT seem to be a complex interplay between direct and indirect (via vascular damage) effects on neoplastic cells according to the intratumoral localization pattern of the applied dye. Several factors can affect the localization pattern of a drug, such as its chemical character, the mode of drug delivery, the time interval between drug administration and light exposure, and tumor type. Furthermore, whether local immune reactions (such as macrophages) and apoptosis (programmed cell death) are involved in the destruction of neoplastic cells by PDT in vivo is still an enigma. A general model for PDT-induced tumor destruction is suggested.

Animals↗
PubMedDate not supplied

Phototoxicity to sulphonamide derived oral antidiabetics and diuretics. Comparative in vitro and in vivo investigations.

The oral antidiabetics chlorpropamide, glibenclamide, glipizide, gliquiudone, glymidine, tolazamide and tolbutamide, and the diuretics bemetizide, bendroflumethiazide, benzylhydrochlorothiazide, bumetanide, butizide, chlortalidone, furosemide, hydrochlorothiazide, hydroflumethiazide, indapamide, piretanide, polythiazide, trichlormethiazide, and xipamide were investigated for potential phototoxicity in vitro using a cell culture model, and in vivo in hairless mice. After exposure to broad band UVA, the majority of the substances tested in vitro yielded a phototoxic action leading to loss of culture forming ability. In vivo, all tested substances induced edema or ulceration, and lead to a significantly increase in skin fold thickness of the mouse skin. In all, a number of substances not described to induce clinical photosensitivity nor phototoxicity in vitro or in vivo were detected in our testing. When determining potential photosensitizers, it seems important to utilize different test methods, as not all substances will exhibit action in a given assay.

Administration, Oral↗