Seiichi Morokuma

Serum Uric Acid Levels Correlate With Plasma Hydrogen Peroxide and Protein Carbonyl Levels in Preeclampsia

BACKGROUND Increased serum uric acid has been postulated to directly promote oxidative stress. The aim of this study was to investigate whether serum uric acid level correlated with superoxide generation and oxidative stress in preeclampsia. METHODS We assessed serum uric acid levels, plasma hydrogen peroxide levels, and plasma protein carbonyl levels in normal pregnant (n = 14) and preeclamptic women (n = 17). Serum uric acid and plasma hydrogen peroxide levels were determined by the uricase-peroxidase method, a combined enzymatic-colorimetric method. Plasma carbonyl levels were measured by ELISA. RESULTS The mean serum uric acid values were significantly elevated in preeclampsia (6.6 +/- 1.5 mg/dl) compared with normal pregnancy (4.0 +/- 0.7 mg/dl) (P < 0.001). Plasma protein carbonyl levels were also significantly elevated in preeclampsia (7.72 +/- 4.10 nmol/mg) compared with normal pregnancy (2.85 +/- 3.06 nmol/mg) (P = 0.0011). In addition, the plasma hydrogen peroxide levels were significantly higher in preeclampsia (66.9 +/- 10.9 micromol/l) compared with normal pregnancy (50.1 +/- 5.6 micromol/l) (P < 0.001). Serum uric acid levels correlated significantly and positively with plasma hydrogen peroxide levels (r(2) = 0.2965, P = 0.0027) and plasma protein carbonyl levels (r(2) = 0.2011, P = 0.0129). CONCLUSION The increased serum uric acid levels correlated closely with plasma hydrogen peroxide levels and plasma protein carbonyl levels in preeclampsia. Therefore, the serum uric acid level serves as an indicator of the underlying oxidative stress in preeclampsia.

Fetal habituation correlates with functional brain development

In this study, we divided 26 fetuses at 32-37 weeks of gestation into three groups using combined criteria of gestational age and behavioral indicators. We investigated fetal habituation to vibroacoustic stimulation (VAS). Fetuses showed habituation from at least 32 weeks of gestation. Furthermore, fetuses less developed from behavioral standpoint took significantly more trials to achieve habituation than developed fetuses even in the same gestational age. Taken together with these data, it was proved that there was a relationship between aspects of behavioral development and habituation.

Short-term and long-term outcomes of 214 cases of non-immune hydrops fetalis.

Despite advances in diagnosis and management, non-immune hydrops fetalis (NIHF) has a high mortality rate. Perinatal survival depends on the underlying disorder and the gestational age at diagnosis. As prognostic information is limited, this study acquired data regarding the neurological development of perinatal survivors. We performed a retrospective chart review of 214 cases in which NIHF was diagnosed antenatally. We recorded maternal demographic characteristics and interventions and their effectiveness, as well as the short-term outcome (survival) and long-term outcome including developmental quotients. Among the affected fetuses, 91 (42.5%) survived the perinatal period. Fetuses with chylothorax, chyloascites, or meconium peritonitis, and those in whom therapy was effective, had high survival rates irrespective of the type of intrauterine intervention. The subsequent intact survival rate was 28/56 (50.0%), with intact defined as ratio of the number of infants with normal development to the number of all infants followed. In contrast to the perinatal survival rate, the intact survival rate decreased as gestational age at diagnosis advanced. These findings suggest that the long-term intact survival rate depends on the underlying cause of NIHF. Additionally, while survival was improved with intensive perinatal care during the perinatal period, aggressive perinatal intervention was not a prognostic factor for neurological outcome.

Characterization of placental transfer of polychlorinated dibenzo-p-dioxins, dibenzofurans and polychlorinated biphenyls in normal pregnancy

Aim:  Prenatal exposure to dioxins may result in many adverse health effects. However, the mechanisms by which dioxins are transferred from mother to fetus through the placenta are not well understood. The aim of this study was to investigate the differences in dioxin concentrations between maternal blood, the placenta, and cord blood in normal pregnant women, and to identify which individual congeners of these compounds are transferred from mother to fetus through the placenta.

Cervical length predicts placental adherence and massive hemorrhage in placenta previa

Aim:  To evaluate the relationship between cervical length (CL) and obstetrical outcome in women with placenta previa.

Prognosis and long-term neurodevelopmental outcome in conservatively treated twin-to-twin transfusion syndrome

BackgroundAmnioreduction remains a treatment option for pregnancies with twin-to-twin transfusion syndrome (TTTS) not meeting criteria for laser surgery or those in which it is not feasible. Amnioreduction is a relatively simple treatment which does not require sophisticated technical equipment. Previous reports of conservative management have indicated that major neurodevelopmental impairment occurs in 14.3-26% of survivors. The purpose of this study was to investigate long-term neurodevelopmental outcome in conservatively treated TTTS.MethodsDuring the nine-year study period from January 1996 to December 2004, all pregnancies with TTTS who were admitted to our center were investigated. TTTS was diagnosed by using standard prenatal ultrasound criteria, and staged according to the criteria of Quintero et al. We reviewed gestational age at diagnosis, gestational age at delivery, the stage of TTTS at diagnosis, and diagnosis to delivery interval. Neonatal cranial ultrasound findings were reviewed and the neurodevelopmental outcomes were evaluated.ResultsTwenty-one pregnancies with TTTS were included. Thirteen pregnancies (62%) were treated with serial amnioreduction. The mean gestational age at delivery was 28 weeks (22 - 34 weeks). The perinatal mortality rate was 42.9%. Twenty survivors were followed up until at least 3 years of age. The mean age at follow-up was 6.3 years (3 - 12 years). Six children (30%) had neurodevelopmental impairment. Four children (20%) had major neurodevelopmental impairment and two children (10%) had minor neurodevelopmental impairment. Children with neurodevelopmental impairment were delivered before 29 weeks of gestation.ConclusionsOur study showed a high rate of perinatal mortality and a high rate of major neurodevelopmental impairment in conservatively treated TTTS. The long-term outcomes for the survivors with TTTS were good when survivors were delivered after 29 weeks of gestation.

Inhibition of AHR transcription by NF1C is affected by a single-nucleotide polymorphism, and is involved in suppression of human uterine endometrial cancer

Involvement of the aryl hydrocarbon receptor (AHR) in carcinogenesis has been suggested in many studies. Upregulation of AHR has been reported in some cancer species, and an association between single-nucleotide polymorphisms (SNPs) of AHR and cancer risk or cancer development has also been reported. This evidence suggests the involvement of some specific SNPs in AHR transcriptional regulation in the process of carcinogenesis or cancer development, but there have been no studies to elucidate the mechanism involved. In this study, we identified the transcription factor Nuclear Factor 1-C (NF1C) as a candidate to regulate AHR transcription in a polymorphism-dependent manner. SNP rs10249788 was included in a consensus binding site for NF1C. Our results suggested that NF1C preferred the C allele to the T allele at rs10249788 for binding. Forced expression of NF1C suppressed the activity of the AHR promoter with C at rs10249788 stronger than that with T. Moreover, expression analysis of human uterine endometrial cancer (HEC) specimens showed greater upregulation of AHR and downregulation of NF1C than those of normal endometrium specimens. Sequence analysis showed HEC patients at advanced stages tended to possess T/T alleles more frequently than healthy women. We also demonstrated that NF1C suppressed proliferation, motility and invasion of HEC cells. This function was at least partially mediated by AHR. This study is the first to report that a polymorphism on the AHR regulatory region affected transcriptional regulation of the AHR gene in vitro. Because NF1C is a tumor suppressor, our new insights into AHR deregulation and its polymorphisms could reveal novel mechanisms of genetic susceptibility to cancer.

Developmental Change in Fetal Response to Repeated Low-Intensity Sound.

The aim of this study was to investigate developmental changes in heart rate response to repeated low-intensity (85 dB) sound stimulation in fetuses between 32 and 37 weeks of gestation. We measured amplitude changes in heart rate as our index of fetal response. At 35 to 37 weeks of gestation, the majority of fetuses showed a deceleratory response at the first trial. Amplitude decreased with further trials using the same stimulus before recovering when exposed to another type of stimulation. In contrast, responses in fetuses at 32 to 34 weeks of gestation were variable across trials and there was no recovery with exposure to another type of stimulation. Our results suggest that fetal habituation of cardiac response changes with developmental age.

Prenatal three-dimensional images of proximal focal femoral deficiency produced by helical computed tomography.

Introduction: Proximal focal femoral deficiency (PFFD) is a rare skeletal disorder characterized by failure in development of the subtrochanteric region of the femoral shaft, with varying degrees of shortening of the proximal femur. Objective: To investigate the potential of helical computed tomography as a prenatal diagnostic tool for bony abnormalities. Case: A 37-year-old Japanese woman was referred to our hospital at 32 weeks of gestation for the evaluation of fetal growth restriction with short femurs. An ultrasound examination revealed the fetus to have short femurs bilaterally with normal echogenicity, and a normal facial profile. Assessment by 3D CT confirmed the absence of the femoral heads bilaterally and also revealed bilateral hip dislocations and oligodactyly of the right hand. The baby was delivered by cesarean section at 37 weeks of gestation, whereupon the diagnosis of PFFD was confirmed. Conclusion: Helical CT is a useful prenatal diagnostic alternative for bony abnormalities that is superior to the conventional sonographic approach.

Spontaneous Resolution of Cystic Hygroma and Hydrops in a Fetus with Noonan’s Syndrome

Many studies have shown that the prognosis of cystic hygroma associated with hydrops fetalis is poor. We report a rare case of fetal cystic hygroma and hydrops fetalis that spontaneously resolved with subsequent delivery at 37 weeks of a living female infant with Noonan’s syndrome. The prognostic significance of prenatal resolution of cystic hygroma and hydrops is uncertain. Serial evaluation of affected fetuses with ultrasound imaging may help clarify pathogenesis of cystic hygroma with associated hydrops, as well as mechanisms underlying spontaneous resolution.