Internal exposure risk due to radiocesium and the consuming behaviour of local foodstuffs among pregnant women in Minamisoma City near the Fukushima nuclear power plant: a retrospective observational study.

OBJECTIVES: This 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. DESIGN: A retrospective observational study of a screening along with a questionnaire survey. SETTING: This study was conducted in an obstetrics and gynaecology service in Minamisoma City in Fukushima, Japan. PARTICIPANTS: Participants included pregnant women who applied for the voluntary internal radiation exposure screening programme. PRIMARY AND SECONDARY OUTCOME MEASURES: Internal 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. RESULTS: Overall, 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%). CONCLUSIONS: Health 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.

Birth Outcomes after the Fukushima Daiichi Nuclear Power Plant Disaster: A Long-Term Retrospective Study.

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 (<2500 g at birth) and preterm births (<37 weeks gestation at birth) were compared pre- and post-disaster, and regression models were conducted to assess for associations between these outcomes and evacuation and food avoidance. A total of 1101 live singleton births were included. There were no increased proportions of low birthweight or preterm births in any year after the disaster (merged post-disaster risk ratio of low birthweight birth: 0.98, 95% confidence interval (CI): 0.64-1.51; and preterm birth: 0.68, 95% CI: 0.38-1.21). No significant associations between birth outcomes and residential area or food purchasing patterns were identified, after adjustment for covariates. In conclusion, no changes in birth outcomes were found in this institution-based investigation after the Fukushima disaster. Further research is needed on the pathways that may exacerbate or reduce disaster effects on maternal and perinatal health.

Influence of progesterone on myometrial contractility in pregnant mice treated with lipopolysaccharide.

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.

Phase I and pharmacokinetic study of S-1 administered for 14 days in a 21-day cycle in patients with advanced upper gastrointestinal cancer.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Phase I pharmacokinetic study of S-1 plus cisplatin in patients with advanced gastric carcinoma.

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.

Expression of iNOS mRNA and inhibitory effect of NO on uterine contractile activity in rats are determined by local rather than systemic factors of pregnancy.

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.