Histological changes and involvement of apoptosis after photodynamic therapy for actinic keratoses.

BACKGROUND: Photodynamic therapy (PDT), which employs a combination of a tumour-localizing photosensitizer and visible light, has been used to treat superficial malignancies in the epidermis. OBJECTIVES: To examine histological changes and the role of apoptosis in lesions of actinic keratosis (AK) after PDT using 5-aminolaevulinic acid (ALA) and excimer dye laser. METHODS: After topical ALA-PDT, biopsy specimens were collected from 18 skin lesions in 15 patients with AK. Paraffin-embedded sections of the skin specimens were stained with haematoxylin and eosin. The detection of apoptosis was performed using a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) method, antiactivated caspase-3 antibody and anti-Fas antibody. RESULTS: One hour after PDT, cells with eosinophilic cytoplasm and markedly stained nuclei were found, and vacuolation of some tumour cells was noted in the lower layer of the epidermis. An infiltrate of lymphocytes and neutrophils was observed in the upper layer of the dermis. One day after PDT, all layers of the epidermis exhibited slightly degenerative necrosis, with shadow cell formation and chromatin condensation around the nuclear membrane in the lower layer of the epidermis. Necrosis in all layers of the epidermis and lymphocyte infiltration in the dermis were found 3 days after PDT. Tumour cells had disappeared and regenerative thickening of the epidermis was observed 7 days after PDT. TUNEL staining revealed apoptosis-positive cells in the epidermis in 8 of 11 specimens obtained 1 day after PDT. Activated caspase-3 expression was noted in the lower layer of the epidermis in four of these eight TUNEL-positive specimens. CONCLUSIONS: Results suggested that apoptosis is involved in tumour cell death after PDT in patients with AK, and that it occurs within 1 day after PDT.

Toxicity of isopropyl alcohol exposure on the nasal mucociliary system in the guinea pig.

The toxicity of isopropyl alcohol (IPA) on the nasal mucosa in the guinea pig was experimentally studied, with special reference to the recovery process of the organ. The results showed that 400 ppm of IPA has an acute effect on the nasal mucosa and the recovery from such degeneration can occur in 2 weeks. When functional and morphological damages were induced by a higher level (5500 ppm) of IPA, it took over 2 weeks for complete recovery from such damage. The conclusion is that the present allowable level of IPA is reasonable from a viewpoint of the effect of short-term exposure to IPA on the nasal mucosa. In addition, a higher level of IPA exposure has a longer-term effect on the nasal mucociliary system in the guinea pig, and workers exposed to such a higher level of IPA should be given careful otolaryngological observation.

An experimental study on the respiratory toxicity of isopropyl alcohol.

Guinea-pigs were exposed to 400 ppm or 5500 ppm of isopropyl alcohol (IPA) for 24 successive hours, and they were killed immediately after the exposure period. The ciliary activities of the nose and trachea were examined. In addition, the epithelium of the nose and trachea was observed by scanning and transmission electron microscopy. The present study showed that exposure to 400 or 5500 ppm of IPA vapor caused deterioration of the ciliary activity and also some pathological changes. Although our study revealed that exposure to 400 ppm of IPA vapor can affect the mucosa of the nose and trachea, the ciliary activity of the 400-ppm exposure group was not too poor and morphological changes were rather mild. Recovery from such degeneration might be rapid. Therefore, our study supports the justification of the allowable IPA level recommended by ACGIH.

Acute effects of isopropyl alcohol exposure on the middle ear mucosa.

Guinea pigs were exposed to 400 ppm or 5500 ppm of isopropyl alcohol (IPA) for 24 successive hours, and then middle ear mucosal samples in both proximal and distal sites to the eustachian tube were obtained for functional and morphological examinations. The ciliary activity was examined according to the photoelectric method of Ohashi and Nakai. The morphology of the middle ear lining was examined by transmission electron microscopy. The results showed that IPA at the allowable level of 400 ppm has an acute effect on the mucociliary system of the middle ear mucosa. Recovery from damage occurs within two weeks. At higher levels of exposure to IPA (more than 10 times the allowable level) moderate deterioration of the ciliary activity and severe damage of epithelial cells were observed and recovery within two weeks was not seen. It is concluded that IPA at the allowable level of 400 ppm does not cause significant middle ear disorders, but workers exposed to higher levels of IPA should be given careful otolaryngological examinations and follow-up observations.

Recovery process of tracheal mucosa of guinea pigs exposed to isopropyl alcohol.

The toxicity of isopropyl alcohol (IPA) on the tracheal mucosa was studied experimentally with special reference to the recovery process of the organ. The results showed that 400 ppm IPA has an acute effect on the mucociliary system in the tracheal mucosa, and that recovery from such degeneration can occur in 2 weeks. When functional and morphological damage was induced by a higher level (5500 ppm) of IPA, recovery did not occur in 2 weeks. The conclusion is that the present allowable level of IPA is reasonable from the viewpoint of the effects of short-term exposure to IPA on the tracheal mucosa. In addition, a higher level of IPA exposure has longer-term effects on the tracheal mucosa, and workers exposed to such a higher level of IPA vapor should be given careful otolaryngological follow-up observations.