Jinro Komura

Inhibitory effect of azelaic acid on neutrophil functions: a possible cause for its efficacy in treating pathogenetically unrelated diseases

SummaryIt has been shown that acne, hyperpigmentation and lentigo malignant are more or less related pathogenetically to reactive oxygen species (ROS). It has recently been reported that azelaic acid is effective in treating these conditions and that it possesses anti-enzymatic and anti-mitochondrial activity, including cytochrome-P450 reductase and 5α-reductase in microsomal preparations with nicotinamide adenine dinucleotide phosphate (NADPH). We therefore investigated the effects of azelaic acid on human neutrophil functions, such as chemotaxis, phagocytosis and ROS generation. ROS generation in a cell-free system was also assessed. The results revealed that neutrophil chemotaxis and phagocytosis as well as ROS generated in a xanthine — xanthine-oxidase system were not significantly changed in the presence of azelaic acid. However, azelaic acid markedly decreased O2−and OH generated by neutrophils. It may be concluded that the reported clinical effectiveness of azelaic acid is partly due to its inhibitory action on neutrophil-generated ROS, leading to a reduction both in oxidative tissue injury at sites of inflammation and in melanin formation.

The effect of aging on cutaneous lipid peroxide levels and superoxide dismutase activity in guinea pigs and patients with burns

Cutaneous lipid peroxide levels and superoxide dismutase (SOD) activity in non-aged and aged guinea pigs were measured between 15 min and 7 days after experimental infliction of burns. Skin burns on non-aged and aged patients were also subjected to these assays. In non-aged guinea pig skin burns, lipid peroxide levels increased from 24 hr to the fourth day after the burn infliction, while SOD activity did not increase but showed a slight decrease 12 hr and 24 hr post-burn. On the other hand, while the aged group showed a more increase in skin lipid peroxide levels compared to that seen in non-aged mice, skin SOD activity began to decrease from 30 min post-burn, the maximum decrease being reached on the second day. The activity did not return to normal by the 7th day. In non-aged patients skin burns showed increases in both lipid peroxide levels and SOD activity, while in aged patients, though they showed a marked increase in lipid peroxide levels, SOD activity remained unchanged. The present study indicated that, although in our recent study, skin SOD activity of healthy elderly people was found to be comparable to that in non-aged individuals, the capacity for induction of SOD activity under oxygen stress differed with age in both guinea pig and human burn sufferers. Furthermore, this induction capacity seemed to vary from species to species.

Experimental burn-induced changes in lipid peroxide levels, and activity of superoxide dismutase and glutathione peroxidase in skin lesions, serum, and liver of mice

SummaryThe lipid peroxide levels and the activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in skin lesions, liver, and serum of mice were measured from the 15th min to 6th day after burns were inflicted on their skin. The lipid peroxide levels in the skin lesions were increased at the 24th h and on the 3rd day after the burns were inflicted. However, the SOD activity did not increase but was significantly decreased from the 30th min to 24th h. GSH-Px activity was almost undetectable in both skin and serum. The lipid peroxide levels in the serum were significantly increased and SOD activity slightly increased at the 4th h. The lipid peroxide levels in the liver were elevated at the 4th h and on the 3rd day although a slight decrease was observed at the 8th h. SOD and GSH-Px activities in the liver increased from the 4th to 24th h. The present study illustrates the changes in both burn-induced lipid peroxides in each organ and the induction mechanisms of the activities of oxygen radical scavenging enzyme, SOD, and lipid peroxide processing enzyme, GSH-Px, which responded to oxygen stress.

Dyskeratotic degeneration of epidermal cells in pityriasis rosea: light and electron microscopic studies

We studied biopsies from twenty‐nine patients with pityriasis rosea. All specimens showed features of subacute or chronic dermatitis as previously reported, but sixteen cases (55%) had dyskeratotic cells within the epidermis. Ultrastructurally, these cells contained an aggregation of tonofilaments, many vacuoles and intracytoplasmic desmosomes. Previously, only non‐speci fic histological changes had been described in pityriasis rosea, but the presence of dyskeratotic cells seems to be a significant feature.

Auto-oxidative damage in cement dermatitis

SummaryOxygen intermediates (OIs) generated by stimulated polymorphonuclear leukocytes (PMNs) are known to induce auto-oxidative tissue damage at the site of inflammation. PMNs from five patients with severe and chronic cement dermatitis generated markedly increased levels of OIs. However, only a slight increase in OI generation by PMNs was observed in cement workers without cement dermatitis. Dapsone, which has recently been shown to decrease OI levels, was found to be clinically effective in the treatment of cement dermatitis in these five patients. After treatment, a significant decrease in OI generation was observed in all patients studied. In skin tissues from the cement workers without cement dermatitis, enhanced superoxide-dismutase (SOD) activities as well as increased OI generation by PMNs were noted. In spite of the greatly increased OI generation by PMNs, the SOD activities in the patients were comparable to those in healthy controls. These findings suggest that the severe skin manifestations in patients with cement dermatitis can partly be explained by a defective capacity for enhancing SOD activity which removes increased PMN-derived OIs and thus prevents subsequent tissue injury by OIs at the site of inflammation.

Effects of Cepharanthin on Neutrophil Chemotaxis, Phagocytosis, and Reactive Oxygen Species Generation

The effects of cepharanthin on inflammatory parameters such as neutrophil chemotaxis, phagocytosis and reactive oxygen species (ROS) generation, were examined. Cepharanthin significantly decreased the levels of O2−, H2O2, and OH. generated by neutrophils. H2O2 and OH. generated in a cell‐free, xanthine‐xanthine oxidase system were also reduced in the presence of cepharanthin. However, the drug did not affect neutrophil chemotaxis or phagocytosis. The present study indicates that cepharanthin is an effective ROS scavenger, exerting its anti‐inflammatory action by reducing the potent ROS species excessively generated in tissues and organs, especially at the sites of inflammation.

Ultrastructural studies of epidermis in acute radiation dermatitis

SummaryFine structural changes of keratinocytes by X-ray were examined in normal skin area around a lesion of Bowens disease. The area was exposed to about 6000 r over 28 days. The findings were: a decreased number of desmosomes and microvilli, formation of cytoplasmic vacuoles with or without membrane, perinuclear aggregation of tonofibrils, intracytoplasmic desmosomes and gap junction, cytoplasmic occurrence of dense bodies, lipid droplet and glycogen particles, changes in mitochondria, endoplasmic reticulum and Golgi complex, and deep invagination of the nuclear membrane. Besides these, conspicuous in the present study were, changes in the basal lamina which consisted of multiplication, thickening and occasional detachment from basal cells, and frequent occurrence of coated vesicles along with the basal lamina alteration. Possible exocytotic nature of coated vesicles in X-ray irradiated keratinocytes is discussed.ZusammenfassungÄnderungen in der Feinstruktur von Keratinocyten durch Röntgenstrahlung im gesunden Umfeld von Hautschädigungen durch Morbus Bowen wurden untersucht. Die Hautpartie wurde mit einer Gesamtdosis von 6000 r innerhalb von 28 Tagen bestrahlt. Gefunden wurde im einzelnen: verminderte Anzahl von Desmosomen und Mikrovilli, Bildung von cytoplasmatischen Vacuolen mit oder ohne Membran, Ansammlung von Tonofibrillen in der Umgebung des Kerns, Desmosomen im Cytoplasma und “gap junction”, Auftreten von “dense bodies”, Lipidtröpfchen und Glykogenpartikel im Cytoplasma, Veränderungen der Mitochondrien, des endoplasmatischen Reticulum und des Golgi-Apparats, tiefe Einschnürungen der Kernmembran. Weiterhin fanden sich bemerkenswerte Änderungen in der mehrschichtigen Basallamina, nämlich Verdickungen und gelegentliche Ablösung von den basalen Zellen sowie häufiges Auftreten von “coated vesicles” verbunden mit der Änderung in der Basallamina. Ein möglicher Exocytose-Charakter der “coated vesicles” in Keratinocyten, die Röntgenstrahlen ausgesetzt worden sind, wird diskutiert.