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SummaryThe correlation between the amount of lipid peroxide and squalene in skin surface lipid was observed by statistical analysis. To investigate the mechanism of skin surface lipid peroxidation, es

Lipid peroxide in human skin surface lipids was investigated. The correlation between the amount of lipid peroxide and the total amount of lipids in skin surface lipids was determined by statistical analysis. Furthermore, the correlation between lipid peroxide and squalene in skin surface lipids was also proved. These results suggest that the major source of lipid peroxide in skin surface is squalene, and that lipid peroxidation is enhanced by external factors such as ultraviolet light irradiation.

We describe a case of photosensitivity due to pyridoxine hydrochloride (vitamin B6) in a heterozygote of hypophosphatasia. Photopatch tests using pyridoxine hydrochloride and pyridoxal 5′-phosphate, compounds referred to as vitamin B6, with ultraviolet light A irradiation were positive. Laboratory examination showed low serum alkaline phosphatase. Tissue-nonspecific alkaline phosphatase exon amplification from DNA of the patient’s lymphocytes detected deletion 1154–1156 hypophosphatasia mutation, indicating that this patient was diagnosed to be a heterozygote of hypophosphatasia. The seric pyridoxal 5′-phosphate level of this patient with hypophosphatasia was higher than in normals. Furthermore, after oral administration of vitamin B6 this level increased greatly and long-lastingly, and this might be related to the low level of alkaline phosphatase in this patient. Photosensitivity in this patient may have been caused by abnormal metabolism of vitamin B6 under the hypophosphatic condition.

To elucidate photosensitization potentials of new quinolone antibacterial agents, production of active oxygen species and peroxidation of squalene after ultraviolet A exposure were investigated. Production of singlet oxygen and/or hydrogen peroxide was estimated by bleaching of p-nitroso-N, N-dimethylaniline. Lomefloxacin showed the greatest ability to produce active oxygen species, and this ability was reduced by the addition of the singlet oxygen quencher sodium azide. Ciprofloxacin and fleroxacin also had strong activity. Photosensitized peroxidation of squalene was evaluated by measurement of thiobarbituric acid-reactive substances. Lomefloxacin was the strongest sensitizer, followed by fleroxacin and ciprofloxacin. These results suggest that certain new quinolones are involved in phototoxicity via the mechanism of active oxygen species.

医薬品として使用されているフェノチアジン誘導体には,長波長紫外線を吸収してヒト皮膚に光線過敏症を誘起するものがある.10位に3-dimethylaminopropyl基をもつクロルプロマジンおよび3-qUinuclidinylmethyl基をもつメキタジンによる皮表脂質スクアレンの光増感酸化反応を調べ,この反応は一重項酸素が関与するTypeII反応であることを明らかにした.両薬剤による不飽和脂質の光増感酸化反応と一重項酸素生成の量子収率に対する溶媒依存性を比較検討した.生体内で起こる光増感反応を生体外でシミュレートするには,反応基質や光増感剤をとりまくミクロな環境を十分に考慮する必要があることを明らかにした.

Human red blood cells (RBCs) were lysed by in vitro irradiation in the presence of the antifungal drug griseofulvin (GF). Effects of UVA fluence and GF concentration on photohaemolysis were examined under aerobic conditions. The photohaemolysis occurred at much lower fluence than that necessary for oxidation of the membrane lipids. UVA-irradiated solution of GF did not cause haemolysis. The photohaemolysis was colloid osmotic in nature because it was preceded by K+ leakage from the cells and was delayed in the presence of 30 mM sucrose in the medium. Even under anaerobic conditions, RBCs were lysed by irradiation with higher fluence than that required for aerobic photohaemolysis. Therefore, some phototoxic mechanism other than photosensitized oxidation is also involved in the photohaemolysis.

The mechanism and active species of drug-induced photosensitive reactions were investigated by measuring the absorption spectra of the transient species on photoexcitation as well as by determining the efficiency of singlet oxygen production on quenching by oxygen of the excited state of drugs. The quantum yields of singlet oxygen production were determined for chlorpromazine hydrochloride, mequitazine, and afloqualone as 0.27, 0.28, and 0.14, respectively. These rather high yields of singlet oxygen suggest its important role in photosensitivity of the drugs. On the basis of the transient-spectroscopic investigations the quenching mechanism of excited-state drugs by oxygen was discussed.

We report here a case of Bowen's disease that developed in the periungual area of the left ring finger of a 55-year-old Japanese male. Because the histology of the lesion mimicked in part the features of a common wart, a PCR-based analysis of human papillomavirus (HPV) DNA and sequencing of viral DNA of PCR-amplified fragments were performed. The lesion contained HPV11 and 16 DNA, and HPV was suspected to play a role in the development of the lesion.

We would like to respond to theArchivesarticles by O'Connor et al 1 and Cribier et al. 2 O'Connor et al reported on the porphyrin abnormalities found in the acquired immunodeficiency syndrome and suggested that the contribution of the hepatitis C virus (HCV) to abnormal porphyrin excretion patterns were characteristic of porphyria cutanea tarda (PCT). In 1994, we analyzed the urinary excretion patterns of porphyrin derivatives in patients with HCV-induced liver disease and HCV carriers using high-performance liquid chromatography. 3 The levels of urinary porphyrins of 63 HCV-positive patients who had liver diseases (including acute hepatitis, chronic hepatitis, liver cirrhosis, and hepatoma), 37 HCV carriers, and 32 healthy volunteers are summarized in the Table. The levels of uroporphyrin were below the detection limit and a coproporphyrin-predominant excretion pattern was observed in all these groups. Only secondary coproporphyria was observed and no PCT-like excretion pattern was observed. To clarify the

Skin surface is covered with very thin lipid film called as skin surface lipids. Skin surface lipids are the mixture of sebum originated from sebaceous gland and epidermal lipids. Epidermal lipid is the minor component of skin surface lipids and occupies less than 5 % of skin surface lipids. However, the epidermal lipids, especially ceramide, play an important role in water barrier function of the skin.

A woman who had ingested honeybee royal jelly as a nutrient, showed an exacerbation of dermatitis when it was applied to her feet. A topical fungicide also aggravated her skin lesions. Patch testing showed positive reactions to the royal jelly, pyrrolnitrin in the fungicide and urushiol. Positive reactions to the royal jelly were found in 2 out of 10 controls, 1 of whom was sensitive to propolis.

— Both DNA bacteriophage and RNA bacteriophage were inactivated when they were irradiated with near-UV light (black light) in the presence of chlorpromazine. The far-UV sensitive mutants of T4D, i.e. T4Dv, T4Dpx and T4Dy, were no more sensitive to near-UV light plus chlorpromazine than the wild type. Electron microscopic observations showed that adsorption of T4D was greatly influenced by the treatment. The present results may indicate that the inactivation of T4D is due to the loss of adsorption caused by impairment in the tail or the tail fiber protein rather than the inactivation of DNA.

— The relative photoinduced toxicity of five benzothiadiazine diuretics was assessed with respect to their potentiality to inactivate bacteriophage lambda by exposure to near-UV light in a semi-aqueous solution of 40% N,N-dimethylformamide. The results showed the following order for the toxicity on a quantum yield basis: penflutizide > trichlormethiazide > methichlothiazide > benzylhydrochlorothiazide > hydrochlorothiazide. Since the bacteriophage was inactivated even when mixed with preirradiated solutions of the diuretics, some photoproducts are responsible for the photoinduced toxicity of the diuretics. Although a lowered pH affected the infectivity, it was a minor factor.

Purine phosphoribosyltransferase activities in normal and experimental hyperkeratotic epidermis of guinea pig skin were demonstrated quantitatively by a new microassay method. The ratio of HGPRTase with hypoxanthine as a substrate to APRTase activity in normal and hyperkeratotic epidermis was found to be 0.94 and 0.60, respectively. The HGPRTase and APRTase activities expressed as μmoles per gram wet weight per min. were increased in experimental hyperkeratotic epidermis and it is suggested that the salvage pathway for purine nucleotide biosynthesis is activated in experimental hyperkeratotic epidermis. The pH optimum of these enzymes and their stability in the frozen state were also demonstrated.

Evidence is presented to show that in the skin of the neonatal rat, the enzyme adenylate kinase is associated with particles. We prepared a lysosomal fraction from neonatal rat skin and then further fractionated this material by the use of a density gradient which varied from 0–16% Ficoll and 0.88–1.4 M sucrose. Three bands were isolated which had acid phosphatase, β-glucuronidase and adenylate kinase activity. Each of these fractions was then resubjected to an expanded density gradient corresponding to the range in which it had previously sedimented. When equilibrium had been reached, the particles still exhibited acid phosphatase, β-glucuronidase and adenylate kinase activity. Repeatedly washed particles retained adenylate kinase activity.

A patient with phytosterolemia and type IIa hyperlipoproteinemia with tuberous xanthomas is described. The plant sterols, beta-sitosterol, campesterol, and stigmasterol, were identified in plasma and the xanthomas; to our knowledge, this is the first case of phytosterolemia and xanthomatosis in a Japanese.

We examined the lipid peroxidative potency and photohemolytic activity of thiazide diuretics, especially penflutizide (PFZ), to determine the molecular mechanism of thiazide phototoxicity. Ultraviolet A irradiation of squalene in the presence of PFZ, hydrochlorothiazide, methiclothiazide, benzylhydrochlorothiazide, or trichlormethiazide induced in vitro peroxidation as measured by production of the hydroperoxides and thiobarbituric acid-reactive substances. Among the thiazides, PFZ showed the highest potency to photooxidize lipids. PFZ-photosensitized peroxidation of squalene was repressed by the presence of sodium azide or 2,5-dimethylfuran and was accelerated in a D2O suspension. These findings suggest the participation of singlet oxygen in PFZ photoperoxidation of squalene (type II mechanism). PFZ-photosensitized lysis of red blood cells (RBC) accompanied by formation of hydroperoxides in RBC membrane lipids was also noted. These results suggest that membrane lipids can be one of the target molecules of thiazide phototoxicity.

Effect of UV-A irradiation on bacteriophage lambda in the presence of afloqualone (AQ) was examined to obtain in vitro evidence for phototoxic potential of AQ, a centrally acting muscle relaxant. Neither AQ itself nor the long-lived photoproducts affected viability of the phage, but the phage was inactivated when it was irradiated in the presence of the drug. Photosensitized inactivation was efficiently repressed by the presence of radical scavengers such as hydroquinone, cysteamine and cystein but not by D-mannitol, benzoate, formate and dimethyl sulfoxide ( • OH scavengers). Methionine also inhibited inactivation as well. Sodium azide and tryptophan followed them, but 1,4-diazabicyclo[2.2.2]octaine (DABCO) did not reduce the inactivation rate. Deuterium effect was not observed. AQ-sensitized photoinactivation occurred even under anoxic conditions although the rate was lower than under aerobic conditions. In view of these results, Type I process is more suitable for explanation of AQ-sensitized photoinactivation than Type II process.

Effects of chlorpromazine plus UVA-illumination on RNA were studied in vitro. Chlorpromazine-UVA treatment of RNA extracted from bacteriophages MS2 and Qβ reduced their infectivity to Escherichia coli spheroplasts. Extent of the inactivation was increased with increasing concentrations of chlorpromazine and with increasing fluence of UVA. In the light of our previous findings, chlorpromazine-adduct to purine residues is suggested as a possible source of damage leading to the inactivation of RNA.

In connection with chlorpromazine-induced skin photosensitivity, chlorpromazine-sensitized photooxidation of squalene was studied in vitro. When squalene (in ethanolic solution or in an aqueous suspension) was irradiated with UV-A light in the presence of chlorpromazine, the yield of peroxidation products was greatly increased. Lines of evidence for the peroxidation were obtained by the iodometric determination and the thiobarbituric-acid method. Gas chromatography indicated that squalene was decomposed by the photosensitized reaction and the remaining amount was decreased exponentially with increasing fluence. The quenching effects of NaN3 and 2,5-dimethylfuran and the enhancing effect of D2O showed participation of singlet oxygen in the photosensitized reaction.

To investigate the response of cells to one type of DNA damage — namely DNA crosslinks — cell-cycle progression and macromolecular synthesis were studied with cultured mouse FM3A cells. Treatment of the cells with low doses of 8-methoxypsoralen (8-MOP) plus near-UV radiation (0.1 μg/ml plus 5 kJ/m 2 or 1.0 μg/ml plus 1–2.5 kJ/m 2 )_halted the progression of cells through the cell cycle temporarily for the first several hours. Then the cells resumed progression through the cell cycle, and most of the cells reached, and were finally arrested at, the G2 phase of the cycle. There was a rapid decrease of incorporation of [ 3 H]thymidine into cellular DNA immediately after the treatment. Then, after 8 h of incubation, the incorporation of [ 3 H]thymidine recovered to some extent depending on the dose of 8-MOP plus near-UV radiation. Thus the decrease and recovery of the incorporation of [ 3 ]Hthymidine were correlated with the halt and resumption in the cell-cycle process. Synthesis of RNA and protein was measured by determination of the amounts in the cells or by the incorporation of radioactive precursors after treatment. RNA and protein synthesis were stimulated by low doses of 8-MOP plus near-UV radiation, but inhibited severely by high doses.

1) Urease solution shows a characteristic absorption in ultraviolet with a maximum at 278 mμ at pH from 6.0 to 8.0.2) The equation, 0 D at 278 mμ×F=Urease (mg/ml), F=1.25 was obtained when urease solution was completely free from acetone.