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Biomedical subjects

I Matsuo

Publications and source records attributed to I Matsuo.

At least 91 records · Page 5Linked to original sources

Afloqualone phototoxicity--photosensitized lipid peroxidative potency and its biological significance.

Photosensitivity due to afloqualone (AQ), a muscle relaxant acting on the central nervous system, has tended to increase with increasing clinical use of this drug by orthopedists. The initial step leading to drug photosensitivity is a photochemical reaction between photo excited phototoxic compounds (drugs) or their metabolites and target molecules in skin. The present study was an attempt to determine whether unsaturated lipids are one of the target molecules of AQ-photosensitivity. Squalene, an unsatulated model lipid, was subjected to UVA irradiation in the presence of AQ and production of squalene hydroperoxides was confirmed. AQ-photosensitized peroxidation of squalene was repressed in the presence of 2.5-dimethylfuran, a singlet oxygen acceptor. Production of singlet oxygen by UVA irradiation of AQ was also observed in aqueous solution. These findings suggested participation of singlet oxygen in the AQ photosensitized peroxidation of squalene. Although photohemolysis was not observed by UVA irradiation in the presence of AQ, We propose that lipids can be a target molecule of AQ-phototoxicity, and lipid peroxidation might be one of the important factors responsible for induction of the AQ phototoxic reaction.

Hemolysis↗

UV-A induced DNA nicking activities of skin photosensitive drugs: phenothiazines, benzothiadiazines and afloqualone.

Plasmid pBR 322 was subjected to UV-A irradiation in the presence of photosensitive drugs, i.e., phenothiazines [chlorpromazine hydrochloride (CPZ), promethazine hydrochloride (PMZ) and mequitazine (MQZ)], benzothiadiazines [penflutizide (PFZ), hydrochlorothiazide (HCT) and methyclothiazide (MCT)] and afloqualone (AQ). The distribution of the closed-circular and the open-circular form of the plasmid DNA was analyzed by means of neutral agarose gel electrophoresis. All the drugs used induced more or less DNA nicking to yield the open-circular form. The nicking activities of the phenothiazines were in the order: CPZ greater than PMZ greater than MQZ. CPZ elicited extensive degradation of the DNA by photosensitization. The nicking activities of the benzothiadiazines and AQ were much weaker than CPZ and PMZ.

Benzothiadiazines↗

Adult T-cell leukemia/lymphoma in pregnancy.

Adult T-cell leukemia/lymphoma, a lymphocytic leukemia caused by human T-cell lymphoma virus-I (HTLV-I), is prevalent in southwestern Japan. A Japanese woman with adult T-cell leukemia/lymphoma in the third trimester of pregnancy was delivered of an infant by cesarean section. She did not breast-feed the child, who has remained free from HTLV-I infection.

Adult↗

Phototoxic potential of afloqualone, a quinazolinone derivative, as determined by photosensitized inactivation of bacteriophage.

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.

Amino Acids↗

Chlorpromazine-sensitized photooxidation of squalene.

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.

Chlorpromazine↗

A case of clear cell adenocarcinoma of the uterine cervix in pregnancy.

An extremely rare case of clear cell adenocarcinoma of the uterine cervix in pregnancy is reported. The primary lesion was first found at 34 weeks of pregnancy in a 34-year-old patient, and was cytologically suspected to be malignant. At 39 weeks of pregnancy, the patient underwent abdominal cesarean section concomitantly with removal of huge right ovarian tumor (3050 g) and delivered a normal male baby weighing 3590 g. Histological findings for cone biopsy at 22 days postpartum revealed invasive adenocarcinoma, and abdominal radical hysterectomy and pelvic lymphoadenectomy were performed at 36 days postpartum. Microscopically, the tumor tissue was composed of clear and hobnail-type cells. It showed a considerable amount of PAS-positive diastase-labile glycogen but was only weakly positive for immunoperoxidase staining of carcinoembryonic antigen.

Adenocarcinoma↗

Phototoxic potential of mequitazine, a phenothiazine derivative, as determined by the photosensitized action on microbiological systems.

In order to determine phototoxic potential of mequitazine (MQZ), a phenothiazine derivative, in vitro tests were attempted using microbiological systems. When Escherichia coli was irradiated with ultraviolet-A light in the presence of MQZ, the surviving fraction was decreased with increasing fluence. Irradiation of bacteriophage lambda in the presence of the drug decreased the surviving fraction as well. Possible targets for the photosensitized action in these systems were discussed.

Bacteriophage lambda↗

Lipid peroxidative potency of photosensitized thiazide diuretics.

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.

Benzothiadiazines↗

Effects of PUVA therapy on skin surface lipids: skin surface lipid peroxidation in psoriasis vulgaris and its biological significance.

PUVA therapy (Psoralen + UVA irradiation) is an effective mode of photochemotherapy for psoriasis vulgaris. The biological significance of PUVA therapy for psoriasis vulgaris has mainly been considered to be based on DNA, especially the formation of DNA crosslinks between complementary DNA stands. On the other hand, we have already reported that skin surface lipids were oxidized by UVA irradiation in vitro and this reaction was enhanced in the presence of 8-methoxy-psoralen by a singlet oxygen mechanism. Keeping this in mind, we conducted an experiment to determine whether lipid peroxide can be formed in skin surface lipids following systemic PUVA therapy in psoriasis patients and the following results were obtained: 1) a marked increase of lipid peroxide values in skin surface lipids occurred following PUVA therapy; and 2) the amount of squalene in skin surface lipids was decreased by this treatment. These results indicate that skin surface lipids can be oxidized by PUVA therapy in vivo and this lipid peroxidation on the skin surface may be related to the effects of PUVA therapy on psoriasis vulgaris.

Adult↗

A case of meconium peritonitis: the pathological findings.

An autopsy case of meconium peritonitis is described. This baby was born at 24 weeks of gestation. The pathological findings were generalized peritonitis and this inflammation spread to the umbilical cord. It can be thought that the cause of premature labor may be in part some inflammatory process.

Female↗

Activities of glycogen synthetase and glycogen phosphorylase in the human endometrium: relative distribution in isolated glands and stroma.

The activities of glycogen synthetase and glycogen phosphorylase were studied in endometrial samples obtained from 51 premenopausal women during the menstrual cycle. The total activities of glycogen synthetase and glycogen phosphorylase and the activity of the active form of glycogen phosphorylase increased gradually from the proliferative phase to the secretory phase and reached a maximum during the midsecretory phase, while the activity of the active form of glycogen synthetase increased slightly. In 30 of the 51 women, the relative distribution of glycogen synthetase and glycogen phosphorylase activities in isolated glands and stromal cells was determined following collagenase digestion of the endometrial specimens. The results indicated that the activities of the active form of glycogen synthetase and glycogen phosphorylase in the isolated glands during the secretory phase were more than threefold and twofold, respectively, greater than those present in the isolated stromal cells and that the levels of these enzymes in the glands and stromal cells changed in parallel with those in the undissociated endometrium observed during the menstrual cycle. In addition, histochemical studies revealed the presence of glycogen phosphorylase activity in both the glands and the stromal cells, whereas the glycogen synthetase activity was present only in the glands. These findings suggest that the stromal cells of the human endometrium as well as the glands may play an important role in the nutrition of the implanting blastocyst.

Cell Separation↗