Zinc coproporphyrin I derived from meconium has an antitumor effect associated with singlet oxygen generation.

INTRODUCTION: Zinc coproporphyrin I (ZnCP-I) is a photosensitive molecule and a major component of meconium. Here, we examined the effects of ZnCP-I as a potential photosensitizer in photodynamic therapy for tumors. MATERIALS AND METHODS: (1) Aqueous ZnCP-I was irradiated with a pulsed YAG-SHG laser (wavelength: 532 nm)/YAG-SHG dye laser (wavelength: 566 nm). (2) HeLa cells were incubated in 200 mM ZnCP-I, and accumulation of ZnCP-I in HeLa cells was evaluated with ZnCP-I-specific fluorescence over 500 nm. (3) Aqueous ZnCP-I was administered intravenously to HeLa tumor-bearing mice at a dose of 10.2 mg/kg body weight. The tumors were irradiated with a filtered halogen lamp (wavelength: 580 nm) at 100 J/cm(2) 20 min after administration. RESULTS: (1) An intense near-infrared emission spectrum was observed at around 1,270 nm after irradiation. The emission intensity was proportional to the laser power between 10 and 80 mW and was completely inhibited by addition of NaN3, a singlet oxygen scavenger. (2) ZnCP-I-specific fluorescence was detected in the HeLa cell cytoplasm. (3) Irradiated tumors treated with ZnCP-I were mostly necrotized. CONCLUSION: ZnCP-I accumulated in tumor cells, produced singlet oxygen upon irradiation, and necrotized the tumor cells. These results suggest that ZnCP-I may be an effective photosensitizer.

Congenital blood coagulation factor XIII deficiency and successful deliveries: a review of the literature.

Congenital deficiency of blood coagulation factor XIII is an uncommon, inherited disorder characterized by hemorrhagic diathesis, habitual abortions and defective wound healing. We analyzed 8 reported successful pregnancies in women with a congenital deficiency of A-subunit of factor XIII (XIIIA), in which the plasma level of maternal factor XIIIA and/or the precise replacement therapies are described. Because decidual bleeding usually begins from 5 to 6 weeks' gestation and, without replacement therapy, spontaneous abortion always occurs, we herein offer the following prenatal and peripartum management guidelines and observations: i) the level of plasma A-subunit of factor XIII antigen (XIIIA-Ag) or factor XIII activity (XIII-act) must be at least 2%-3%, and, if possible, higher than 10% to prevent decidual bleeding and miscarriage during the pregnancy; ii) factor XIIIA concentrate is better than fresh frozen plasma or cryoprecipitate for replacement therapy; iii) the administration of 250 international units (IU) every 7 days is sufficient to maintain the level of plasma XIIIA-Ag or XIII-act more than 10% in the early period of gestation (through 22 weeks' gestation); however, 500 IU every 7 days is indicated in the later period (from 23 weeks' gestation) to maintain that level; iv) during labor, the desired level of plasma XIIIA-Ag or XIII-act should be higher than 20%, and, if possible, higher than 30% in order to make ready for any risk of severe obstetrical hemorrhagic complications; thus a booster dose of 1000 IU is indicated before labor; v) no replacement therapy is necessary in the puerperium because it is usually uneventful without it.

Congenital blood coagulation factor XIII deficiency and perinatal management.

Transglutaminases are at least 9 enzymes which cross-link a number of proteins. This type of reaction not only enhances the original functions of substrate proteins, but also adds new functions to them. Factor XIII (FXIII) is a plasma transglutaminase circulating in blood as a heterotetramer and consisting of two catalytic A subunits and two non-catalytic B subunits. It is a proenzyme activated by thrombin in the blood coagulation cascade. It plays an important role(s) in hemostasis, wound healing, and maintenance of pregnancy. Accordingly, a lifelong bleeding tendency as well as abnormal wound healing and recurrent spontaneous miscarriage are common symptoms of FXIII deficiency. Genetic and molecular mechanisms of congenital deficiencies have been analyzed in vitro. The mechanisms of these defects have also been studied in detail by using FXIII gene knock-out mice in vivo. We analyzed eight successful outcomes of pregnancy in patients with congenital deficiency of FXIIIA, in which the plasmatic level of maternal FXIIIA and/or the precise substitute therapies were mentioned. Then we propose the following guidelines for the perinatal management: (i) decidual bleeding usually begins from 5 weeks of gestation and spontaneous abortion always occurs subsequently without substitute therapy; (ii) the plasma level of FXIIIA must be at least 2 approximately 3%, however, if possible, higher than 10% to prevent bleeding and miscarriage; (iii) the administration of 250 IU of FXIIIA concentrate each 7 days is enough to keep the level of plasma FXIIIA more than 10% in the early gestation, however 500 IU each 7 days is adequate in the later period to keep that level; (iv) during labor, the desired level is higher than 20%, if possible, higher than 30% to avoid any risk of strong obstetrical bleeding.

Morphological analyses of interleukin-8 effects on rat ovarian follicles at ovulation and luteinization in vivo.

The aim of the present study was to elucidate functions of the interleukin (IL)-8 at ovulation and luteinization in vivo. To compare the morphological differences between human chorionic gonadotropin (hCG) and IL-8 stimulation, scanning electron microscopy was employed to study rat ovarian vascular corrosion casts. Follicular growth and increased capillary vessel densities around the follicles were seen in vascular corrosion casts after IL-8 injection, similar to the result of hCG administration. This result indicated that exogenous IL-8 could play a role in the neovascularization during follicular development as an angiogenetic factor. Many fenestrations were observed in the vascular endothelium by hCG administration. In contrast, no fenestrations were observed with IL-8 injection, indicating that IL-8 may not be sufficient to increase the vascular permeability directly. Although germinal vesicle breakdown (GVBD) occurred at rates of 82% after the hCG injection, only 20% GVBD was observed after the IL-8 injection. The present study indicated that IL-8 might have important effects on rat follicles at ovulation and luteinization via vascularization in a similar manner to hCG. However, IL-8 was not effective on vascular permeability and oocyte maturation, which were different from hCG. Thus, we can conclude that IL-8 can participate in follicular development in part and may play important roles in ovulation and luteinization as one of some mediators induced by endogenous luteinizing hormone.