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ObjectivesThis study aimed to evaluate the internal cesium (Cs) level among pregnant women in Minamisoma City (the area straddling the evacuation zones) over a 5-year period after Japan’s 2011 Fukushima nuclear accident and assess the status and transition of their food-acquiring preferences during this period.DesignA retrospective observational study of a screening along with a questionnaire survey.SettingThis study was conducted in an obstetrics and gynaecology service in Minamisoma City in Fukushima, Japan.ParticipantsParticipants included pregnant women who applied for the voluntary internal radiation exposure screening programme.Primary and secondary outcome measuresInternal radiation exposure was evaluated using the whole-body counter (WBC) in the screening programme. Data from a food acquisition preference questionnaire administered to the participants were analysed and compared across the 5-year period after adjusting for covariates.ResultsOverall, 804 screening programmes were conducted with 579 participants during the study period. All participants had internal contamination levels below the detection limit of the WBC unit (220 and 250 Bq/body for Cs-134 and Cs-137, respectively). Based on the most conservative assumption, their maximum annual effective doses by Cs-134 and Cs-137 together were estimated at 16 µSv/year. Contrary to limited internal contamination risks and counter-dose initiatives by the government, a considerable number of pregnant women were still concerned about consuming potentially contaminated local food products when purchasing them at supermarkets between 2012 (78.4%) and 2015 (75.0%).ConclusionsHealth effects from post-accident internal radiation exposure were likely to be insignificant in pregnant women. National/local action is urgently needed to promote scientific understanding in pregnant women regarding limited internal exposure risks from local food products in the market. However, few mothers chose to participate in the internal radiation exposure screening programme, and thus, caution is required in interpreting the results of analyses.

Changes in population birth outcomes, including increases in low birthweight or preterm births, have been documented after natural and manmade disasters. However, information is limited following the 2011 Fukushima Daiichi Nuclear Power Plant Disaster. In this study, we assessed whether there were long-term changes in birth outcomes post-disaster, compared to pre-disaster data, and whether residential area and food purchasing patterns, as proxy measurements of evacuation and radiation-related anxiety, were associated with post-disaster birth outcomes. Maternal and perinatal data were retrospectively collected for all live singleton births at a public hospital, located 23 km from the power plant, from 2008 to 2015. Proportions of low birthweight (

AIM To evaluate the effect of progesterone on interleukin (IL)-6, prostaglandin (PG) E2 and nitric oxide (NO) metabolite (NOx) production and contractile activity by NO in pregnant mice treated with lipopolysaccharide (LPS). METHODS Pregnant C57BL mice on day 14 of gestation were killed 6 h after i.p. injection of LPS (400 microg/kg) or vehicle. Progesterone (2 mg) was subcutaneously injected 2 h before LPS treatment. Uterine rings were equilibrated in Krebs-Henseleit solution (37 degrees C) bubbled with 20% O2 and 5% CO2 (pH 7.4) for sampling and isometric tension recording. IL-6, PGE2 and NOx productions were measured from the bathing solution. Changes in spontaneous contractile activity in response to cumulative concentrations of l-arginine, diethylamine/nitric oxide (DEA/NO, the NO donor), and 8-bromo-cGMP (8-br-cGMP) were compared. Integral contractile activity over 10 min after each concentration was calculated and expressed as percentage change from basal activity. Statistical analyses were performed using one-way anova followed by Dunnett's test (significance was defined as P < 0.05). RESULTS Interleukin-6 (34.7 +/- 6.0 pg/g tissue), PGE2 (66.8 +/- 6.7 pg/g tissue) and NOx (51.0 +/- 5.4 pmol/2 mL/g wet tissue) production were significantly stimulated by LPS treatment (138.2 +/- 23.2, 147.0 +/- 29.0, 98.6 +/- 16.2, respectively; P < 0.05). L-arginine, DEA/NO and 8-br-cGMP concentration-dependently inhibited spontaneous contractions in uterine rings both in LPS-treated and -untreated animals. Treatment with LPS significantly attenuated the maximal inhibition induced by l-arginine, DEA/NO and 8-br-cGMP in uterine rings from pregnant mice. Progesterone significantly decreased the levels of IL-6 production (74.9 +/- 12.1, P < 0.05), but not PGE2 and NOx production, and contractile responses by l-arginine, DEA/NO and 8-br-cGMP. CONCLUSIONS The administration of LPS is associated with increases in IL-6, PGE2 and NO, and these increases may or may not have a role to play in LPS-induced preterm labor. Progesterone reduced the LPS-induced increase in IL-6 production and this may be one of the ways that progesterone reduces the risk of preterm labor.

S-1 is a novel oral fluoropyrimidine that combines tegafur with CDHP and oxonic acid. To decrease the incidence of late onset, severe diarrhea observed in a previous study, a phase I study was conducted to determine the maximum tolerated dose (MTD) of S-1 utilizing a 14-day schedule, repeated every 21 days, in patients with chemotherapy-refractory upper gastrointestinal malignancies.S-1 was administered orally, twice-daily, at an initial dose level of 30 mg/m2/dose; doses were escalated by 5 mg/m2 at each level. A minimum of three patients were enrolled at each dose level. S-1 toxicity, antitumor activity, and pharmacokinetics were assessed. The MTD was based on the dose limiting toxicity (DLT) during the first treatment cycle.At 30 mg/m2 no DLT was observed in the first three evaluable patients. Two of the first three patients at the 35 mg/m2 dose level developed DLTs (grade 3 rash and dehydration). An additional nine patients were subsequently treated at 30 mg/m2 without DLT and this dose was established as the MTD. Common toxicities at 30 mg/m2 included diarrhea, nausea, skin rash, anorexia, and fatigue. No grade 4 toxicities were observed. One partial response was seen in a patient with gemcitabine-refractory pancreatic adenocarcinoma and ten patients with pancreatic, gastric, or gallbladder carcinomas achieved stable disease as their best response to therapy. The AUC(0-8) of 5-FU at the 30 and 35 mg/m2 dose levels were 875 +/- 212 and 894 +/- 151 h ng/ml, respectively.In a 14-day dosing schedule, the MTD of S-1 was 30 mg/m2 and preliminary evidence of antitumor activity was seen in a North American population with refractory upper gastrointestinal malignancies.

Purpose The conversion rate of tegafur (a component of S-1) to fluorouracil (FU) differs in Asians and whites because of polymorphic differences in the CYP2A6 gene. S-1 with cisplatin is considered highly active in Japanese gastric cancer patients. Therefore, we initiated a phase I pharmacokinetic study of this combination in our gastric cancer patients. Patients and Methods Patients received cisplatin intravenously on day 1 and S-1 orally, twice daily, on days 1 to 21 every 28 days. At level 1, the S-1 dose was 25 mg/m2/dose (50 mg/m2/d), but it was increased by 5 mg/m2/dose for the next level. Cisplatin was administered at 75 mg/m2 (for levels 1 and 2) but was then reduced to 60 mg/m2 (level 1A). At every level, a cohort of three patients, which could be expanded to six patients, was studied. Maximum-tolerated dose (MTD) was determined based on the dose-limiting toxicity (DLT) in the first cycle. Patients with histologic proof of gastric adenocarcinoma and near-normal organ function were studied. Results Sixteen patients were enrolled. No DLTs occurred at level 1. However, DLTs occurred at levels 2 and 1A. The area under the curve for FU correlated significantly with DLT (P = .006) and grade 3 to 4 diarrhea (P = .004). Six partial responses were confirmed, including three at the MTD. Conclusion At the established MTD of S-1 plus cisplatin, the S-1 dose (50 mg/m2/d for 21 days) is lower in our study than in the Japanese study (80 mg/m2/d for 21 days). A multi-institutional phase II study of this active combination is currently accruing patients.

We studied the expression of inducible nitric oxide (NO) synthase (iNOS) and soluble guanylate cyclase (sGC) mRNAs in pregnant rat myometrium. Expression of iNOS and sGC alpha1, beta1 and beta2 mRNA was analyzed in non-pregnant and pregnant (days 10, 14, 17 and 21) Wistar rats by reverse transcription-polymerase chain reaction. Expression of iNOS mRNA increased during pregnancy but decreased on day 21 of gestation. Expression of GC alpha1 mRNA was greater than GC beta1 mRNA at all time points. Expression of uterine GC alpha1 and GC beta1 mRNA did not change significantly during pregnancy and did not differ significantly from non-pregnant levels. The values of sGC beta2 mRNA were below the limit of detection. In conclusion, the expression of iNOS mRNA increased during pregnancy in the myometrium and decreased at term, while the expression of sGC mRNA was not affected by pregnancy. Thus, it is the changes in NO production, rather than changes in its target, that are responsible for uterine quiescence during pregnancy and initiation of labor.

Our purpose was to investigate whether the local or systemic factors of pregnancy are associated with inducible nitric oxide synthase (iNOS) mRNA expression and to determine the inhibitory effects of pharmacological agents that increase cGMP levels in rat myometrium. iNOS mRNA expression was determined in uterine tissues from nonpregnant rats and on day 17 of gestation in the pregnant and non-pregnant uterine horns by RT-PCR. In addition, uterine rings from the pregnant and non-pregnant uterine horns were placed in Krebs-Henseleit solution for isometric recordings of spontaneous contractions. Concentration-inhibition relationships to diethylamine/nitric oxide complex, 8-bromo-cGMP, and the selective phosphodiesterase V inhibitor were obtained. Compared to nonpregnant rats, expression of iNOS mRNA in myometrium increased during pregnancy, which was maximal on day 17, followed by a decrease on day 21 of gestation. Expression of iNOS mRNA at day 17 of gestation was greater in pregnant uterine horns than in nonpregnant ones. Maximal inhibition of phosphodiesterase V and increasing cGMP induced similar inhibition of spontaneous contractions in nonpregnant and pregnant uterine horns, while NO induced less inhibition in the former. The results suggest that the local pregnancy factor is needed for signal transduction from NO to soluble guanylate cyclase at a time when maximal expression of iNOS mRNA is evident. Keywords:: iNOS mRNA, nitric oxide, contractility, pregnancy, uterus

s / Placenta 35 (2014) A1eA23 A22 risk of stillbirth at GWNwas defined as a number of womenwith stillbirth at GW. N divided by number of women giving birth at GW N. Results: A total of 32 (29.4%) women experienced stillbirth at median GW of 31 (range, 24±38). Preterm birth (GW37) occurred in 52 (67.5%) of the 77 live born infants. Only 25 (22.9%) women had full-term (GW37) live-born infants. The prospective risk of stillbirth was 29.4% (32/109), 27.5% (25/91), 20.9% (14/67) and 13.0% (6/46) for womenwho reached GW 24, 28, 32, and 36, respectively. Conclusions: As womenwith PMD faces at an extraordinary higher risk of IUFD, early admission to the hospital and intensive monitoring of foetal status should be considered, although whether this policy improves outcome has not been validated. O-097. RADIOACTIVE CESIUM AND POTASSIUM LEVELS IN HUMAN PLACENTA: AFTER THE FUKUSHIMA NUCLEAR POWER PLANT ACCIDENT Makoto Kawamur , Hiroshi Anbe , Fujimori Keiya . a Fukushima Medical University, Department of Obstetrics and Gynecology, Japan; Minamisoma City General Hospital, Department of Obstetrics and Gynecology, Japan Background: The Great East Japan earthquake (followed by large-scale tsunamis) struck Northeastern Pacific Coast of Japan on Mar 11, 2011. It caused TEPCO's Fukushima Daiichi Nuclear Power Plant (NPP) accident, accompanied by radioactive pollution in Fukushima prefecture. Minamisoma City General Hospital, just 23km away from the NPP, restarted the Obstetric services in April 2012. We examined the placental radioactive Cesium and Potassium levels. Methods: We measured the radioactive contents of the 40samples of placenta after the delivery, using high-purity Germanium detectors for Gamma-ray spectrometry (at National Institute of Public Health, Wako, Saitama). All the parturients underwent the Whole-Body Counting (WBC) test of radioactivity. Results: The radioactive content levels are as follows. 134Cs: 0.36Bq/kg, 137Cs: 0.58Bq/kg, total-Cs: 0.94Bq/kg, 40K (natural radioactive): 53.1Bq/kg. Radioactive Cs (from the NPP accident) levels were about 1/50 of the natural radioactive, and much lower than the '87 Italian data, 2years after the Chernobyl NPP accident (total-Cs:11.5Bq/kg). All of the parturients were negative on the WBC test (with cut-off value of 250Bq/body). Conclusion: The Cs levels were much lower than natural radioactive (40K) level, which suggests the efforts to reduce external/internal radioactive exposure in the area has been successful. O-102. DENTAL INFECTION OF PORPHYROMONAS GINGIVALIS INDUCES PRETERM BIRTH Mutsumi Miyauchi , Hisako Furusho , Atsuhiro Nagasaki , Satoshi Urabe , Haruhisa Konishi , Hiroshi Miyoshi , Yoshiki Kudo , Takashi Takata . Department of Oral and Maxillofacial Pathobiology, Institute of Biomedical and Health Sciences, Hiroshima University, Japan; Department of Obstetrics and Gynecology, Hiroshima University, Japan Objectives: Epidemiological studies revealed a link between periodontal disease and preterm delivery, however, the mechanism of the link remains unclear. The present study was aimed to examine the influence of Porphyromonas gingivalis (Pg): one of main periodontal pathogens) on preterm birth with a Pg dental infection mouse model and in vitro analyses with trophoblasts and related cells Methods: In vivo experiment: 8-wksold\C57Bl/6J mice were infected with Pg-w83-strain (108 CFU) from the pulp chamber (Pg group). Mating was started at 6-wks post-infection when a periapical granuloma was established. Gestational day (gd) and birth weight were examined.; At gd15, placental tissues were harvested for IHC staining and PCR. Serum, placental tissue and amniotic fluid were collected for ELISA of cytokines. Uninfected mice were used as negative control (NC). In vitro experiment: HTR-8 (trophoblast), HuhT1 (endothelial cell) and THP1 (monocyte) cell lines were used to assess the effects of Pg and Pg-LPS. Results: Pg group showed 2 days of preterm birth (p

4066 Background: S-1 is a novel oral fluoropyrimidine drug that combines tegafur, CDHP, and oxonic acid (Oxo). A previous phase I study of S-1 bid for 28 days in a 35-day cycle had late onset grade 3/4 diarrhea as the major DLT. In an attempt to decrease this toxicity and reduce the impact of food intake on Oxo stability, we conducted the following phase I study. Methods: S-1 was administered orally one hour before or after a meal bid for 14 days, followed by a 7-day recovery period. MTD, Pharmacokinetics (PKs) and antitumor activity were evaluated. Key eligibility criteria included adult patients with refractory AUGIC, KPS ≥ 50%, and adequate organ function. Results: Sixteen patients were evaluated at two dose levels (30 mg/m2 and 35 mg/m2): median age = 56, Male/Female = 12/4, KPS 100/90/80/70/50 = 6/3/3/3/1. At 30 mg/m2 dose level, no DLT was observed in the first 3 patients. However, two of the three patients developed DLTs (Grade 3 rash and dehydration) on the 35 mg/m2 dose level. An additional 10 pa...

496 ADENYLYL CYCLASE MRNA EXPRESSION AND EFFECTS OF ADENYLYL CYCLASE CASCADE ON CONTRACTILITY IN UNILATERAL PREGNANT RAT MYOMETRIUM KIMISATO ASANO 1, TOSHIAKI OKAWA t, HIDENORI TAKAHASHI 1, SATOSHI HASHIMOTO 1, HIROSHI ANBE t, AKIRA SATO I, YURI VEDERNIKOV~, GEORGE SAADE 2, ROBERT GARFIELD 2, YOSUKE SUZUKI t , ISAO MATSUOKA3; ]Fukushima Medical University, Obstetrics and Gynecology, Fukushima; 2University of Texas Medical Branch, Obstetrics and Gynecology, Galveston, TX; 3Fukushima Medical University, Pharmacology, Fukushima OBJECTIVE: To determine the effect of gestation on adenylyl cyclase (AC) mRNA expression, and on the response to protein kinase C (PKC) and a2 adrenergic agonists in gravid and non-gravid uterine horns of pregnant rats. STUDY DESIGN: Non-pregnan t and day 17 p regnan t Wistar rats were used (n = 6 per group) . In the p regnan t animals, one of the oviducts was ligated before mating in order to result in pregnancy in only one uterine horn. mRNA levels of AC2, AC4, AC6 ad AC9 were determined in the uterine horns with (fetus+) and without (fetus-) fetuses by semi-quantitive reverse transcription-polynaerase chain react ion (RT-PCR). In addit ion, strips of myometr ium fi-om the fetus+ and fetussides were p repa red for isometric tension recording in F-a'ebs-Ringer solution (37°C). The strips were treated with PK-C st inmlant (phorbol myristate acetat: PMA; 1 ~tM) or an a 2 adrenerg ic agonis t (UK-14304; 1 IxM). The changes of contracti l i ty were determined as %change from basal contractile activity. RESULTS: mRNA levels of AC4, AC6 and AC9 were no t significantly different between fetus+ and fetussides on day 47 of gestation. AC2's mRNA levels on the fetusside was significantly lower than the fetus+ side, and were not significantly different than the mRNA levels in the uteri of non-pregnant animals. Uterine contractil i ty was significantly decreased by PMA and UK14304 on the fetus+ side, but was not affected on the fetusside. CONCLUSION: Pregnancy increases AC4, AC6 and AC9 mRNA expression in the uterus by systenfic factors, but the gestational increase in AC2 is dependent on the local presence of pups. AC2 inhibits uterine contractility via a PKC and an ~2 adrenergic receptor in preglmnt myometrium. O f the various adenylyl cyclases, AC2 appears to play the d o m i n a n t role in mainta ining uter ine quiescence in pregnancy. Local factors affecting AC2's expression or function may initiate term or pre term labor. SMFM Abstracts S217

1. 1. The collagen content in different parts of body muscle of fishes with different swimming modes, including anguilliform swimmers, Japanese eel and stone flounder; subcarangiform swimmer, red sea bream; carangiform swimmer, chub mackerel; thunniform swimmer, bluefin tuna, was examined in order to elucidate the biological significance of the muscle collagen of fish. 2. 2. The results indicate that the collagen content and its distribution pattern in body muscle are closely related to swimming modes of fishes and that the flexible body musculature comprises a high proportion of collagen.