Biomedical subjects

Johan Moan

Publications and source records attributed to Johan Moan.

57 records · Page 4Linked to original sources

PubMedDate not supplied

In vitro and in vivo photosensitization by protoporphyrins possessing different lipophilicities and vertical localization in the membrane.

Photodynamic therapy (PDT) is being evaluated in clinical trials for treatment of various oncologic and ophthalmic diseases. The main cause for cell inactivation and retardation of tumor growth after photoactivation of sensitizers is very short-lived singlet oxygen molecules that are produced and have limited diffusion distances. In this paper we show that the extent of biological damage can be modulated by using protoporphyrin, which was modified to increase its lipophilicity, and which also places the tetrapyrrole core deeper within the membrane by the carboxylate groups being anchored at the lipid:water interface. The uptake of the parent molecule (PPIX) and its diheptanoic acid analogue (PPIXC6) by WiDR and CT26 cells was investigated by fluorescence microscopy and by fluorescence intensity from the cells. The uptake of PPIXC6 increased almost linearly with incubation length for over 24 h, whereas for PPIX only 1 h was needed to reach maximal intracellular concentration. Fluorescence microscopy of both cell lines indicated that both drugs were distributed diffusely in the plasma membrane and cytoplasm, but remained outside the nucleus. The efficiency of in vitro inactivation of WiDr and CT26 cells increased with the length of the alkylcarboxylic chain. Tumors in mice that were treated with PPIX-PDT grew more slowly than control tumors. However, tumors that were given PPIXC6 followed by light exposure showed a significant delay in their growth.

Biological Transport↗

PubMedDate not supplied

Photodegradation of 5-methyltetrahydrofolate: biophysical aspects.

5-methyltetrahydrofolate (5MTHF) absorbs UV radiation and has an absorption coefficient of 24250+/-1170 M(-1) cm(-1) at 290 nm. It has a weak fluorescence emission in the wavelength region around 360 nm. Our data demonstrated induction of 5-methyldihydrofolate by exposure to UVB and, after continues irradiation, p-aminobenzoyl-L-glutamic acid was found. The photodegradation of 5MTHF follows a first order kinetic with a degradation rate constant of 9.2 x 10(-3) min(-1) under our conditions (fluence rate of 2.15 mW cm(-2), exposure wavelengths from 280 to 350 nm). Our results indicate that a direct degradation of 5MTHF by UV exposure in humans in vivo is rather unlikely. 5MTHF mainly absorbs, and is degraded by, UVB and UVC, radiation that does not penetrate the earth's atmosphere and the human skin well.

Folic Acid↗

PubMedDate not supplied

An outline of the hundred-year history of PDT.

Photosensitizing drugs have been known and applied in medicine for several thousand years. However, the scientific basis for such use was vague or non-existent before about 1900. Photodynamic therapy, PDT, has now become an established treatment modality for several medical indications. Notably, in the cases of skin actinic keratosis, several forms of cancer and blindness due to age-related macular degeneration, PDT has been successful. PDT is the combined application of a lesion-localizing photosensitizer and light. PDT with porphyrin derivatives as photosensitizing drugs was developed from about 1960. The basic, underlying mechanisms for tumour localization of photosensitizers and processes explaining the effect of PDT on tumours were elucidated from about that time. It has become clear that PDT is efficient only in the presence of oxygen, and that the oxygen dependency of PDT is similar to that of X-rays. Singlet oxygen, 1O2, a short-lived product of the reaction between an excited sensitizer molecule and oxygen, plays a key role. In contrast to radiation therapy and chemotherapy, PDT has a low mutagenic potential and, except for skin phototoxicity, few adverse effects. Approvals for clinical use of PDT now exist in many countries. The annual number of scientific articles on PDT, clinical as well as basic, steadily increases and new aspects and applications of it continue to be discovered. Many of the new investigators are obviously not aware of the early work in the field and repeat many of the experiments that had been reported before the Internet and modern data bases were established. Therefore, in the present historical review, the early work is weighted more heavily than recent work that is more easily accessible to the readers.

Animals↗