Eriko Fujii

Post-ischemic hypothermia blocks caspase-3 activation in the newborn rat brain after hypoxia–ischemia

The effects of hypothermia on caspase-3 activation were investigated in the newborn rat brain after hypoxia-ischemia (HI). Intense caspase-3 activation was observed in the control brains after HI, but this activation was significantly reduced by postischemic hypothermia. These findings suggest that the inhibition of caspase-3 activation may be an interventional point underlying the neuroprotective effect of hypothermia in neonates.

Effects of neonatal hypoxic–ischemic brain injury on skilled motor tasks and brainstem function in adult rats

In an attempt to establish more sensitive long-term neurofunctional measurements for neonatal hypoxic-ischemic brain injury, we examined skilled motor task and brainstem functions in adult rats after neonatal cerebral hypoxia-ischemia (H-I), using a staircase test and auditory brainstem response (ABR), respectively. Seven-day-old rats underwent a combination of left common carotid artery ligation and exposure to 8% O(2) for 1 h (n=16). The control animals only received sham operation (n=16). At 3 months of age, the staircase test and ABR were performed. In the staircase test, H-I animals showed marked impairment of skilled forelimb use in the side contralateral to the occluded artery, and the degree of brain damage correlated significantly to skilled forelimb use. In the ABR, H-I animals showed brainstem dysfunction assessed by measuring interpeak latencies for waves III-V and I-V. We also examined the brainstem with antibodies specific for activated caspase-3, a protein involved in initiation of apoptosis, and observed that caspase-3 was activated in the ipsilateral inferior colliculus at 24 h after H-I. The present study shows that both the staircase test and ABR are sensitive and objective long-term neurofunctional measurements that can be used in future studies to assess therapeutic intervention in this neonatal cerebral H-I model.

Effects of hypothermia on neonatal hypoxic-ischemic brain injury in the rat: phosphorylation of Akt, activation of caspase-3-like protease

Neuroprotective mechanisms of hypothermia have not been clearly established especially in the immature brain. To investigate the effect of hypothermia on cell death and cell survival signal pathways, we studied caspase-3-like activity and activation of Akt in a rat model of neonatal hypoxic-ischemic (H-I) brain injury. Seven-day-old rats underwent a combination of left common carotid artery ligation and exposure to 8% O(2) for 1-h (n=32). During recovery, the body temperature was reduced to 30 degrees C for 24 h in 16 animals, but was kept at 37 degrees C in 16 animals. Post-ischemic hypothermia was shown to diminish the caspase-3-like activity compared to normothermia at 6 and 24 h after H-I. Phospho-Akt was increased during the early reperfusion period after H-I in the normothermia group, but hypothermia rather decreased this enhanced phosphorylation of Akt following H-I. These results indicated that hypothermia may have some depressant effects on both cell death and cell survival signal pathways, and that Akt conceivably may not play a major role in the neuroprotective effect of hypothermia in the immature brain.

The measurements of RAGE, VEGF, and AGEs in the plasma and follicular fluid of reproductive women: the influence of aging

OBJECTIVE To examine the advanced glycation end products (AGEs), the soluble isoform of the receptor for AGEs (sRAGE), and vascular endothelial growth factor (VEGF) concentrations in plasma and follicular fluid (FF) from reproductive-age women. DESIGN Clinical preliminary study based on the regulations of the ethical committee at National Center for Child Health and Development (NCCHD). SETTING Womens health clinical office at NCCHD and Aska clinic. PATIENT(S) Reproductive-age women, young group (<35 yrs) and old group (>or=35 yrs), who agreed to let us use plasma or FF samples for the measurements of AGEs, sRAGE, and VEGF. MAIN OUTCOME MEASURE(S) Measurements of AGEs, sRAGE, and VEGF in plasma and FF by ELISA to examine the difference by aging and reproductive dysfunction. RESULT(S) The plasma concentration of sRAGE was significantly higher in the young group; VEGF in FF was significantly higher in the old group. sRAGE in FF showed a tendency of positive correlation with the number of oocytes. The plasma sRAGE concentration was significantly correlated positively with FF sRAGE and inversely with FF VEGF at the time of egg collection. CONCLUSION(S) The measurement results suggest a possibility that RAGE-VEGF regulation may be related to reproductive dysfunction in aging women, and that plasma sRAGE might be a biologic marker of reproductive condition.

Concentrations of Receptor for Advanced Glycation End Products, VEGF and CML in Plasma, Follicular Fluid, and Peritoneal Fluid in Women With and Without Endometriosis

The etiology and pathogenesis of endometriosis is largely unknown. It has been reported that advanced glycation end products—receptor for advanced glycation end products regulation relates to oxidative stress, inflammatory reaction, apoptosis, and angiogenesis through vascular endothelial growth factor activation. The purpose of this study was to examine whether advanced glycation end products—receptor for advanced glycation end products regulation contributes to the pathogenesis of endometriosis. Plasma, follicular, and peritoneal fluid samples were collected from women with or without endometriosis, and soluble receptor for advanced glycation end products, vascular endothelial growth factor and carboxymethyl lysine levels were measured by enzyme-linked immunosorbent assay. Vascular endothelial growth factor and soluble receptor for advanced glycation end products concentrations were similar in plasma; however, their concentrations in follicular fluid were significantly increased in endometriosis patients (soluble receptor for advanced glycation end products was 132 + 31 pg/mg of protein vs. 105 + 27 pg/mg; vascular endothelial growth factor was 70 + 3 pg/mg vs. 49 + 18 pg/mg, expressed as the mean + standard deviation). Increased soluble receptor for advanced glycation end products and vascular endothelial growth factor levels in a local environment suggest that the advanced glycation end products—receptor for advanced glycation end products may contribute to the pathogenesis of endometriosis.

A Comparative Study of Intraplacental Villous Arteries by Latex Cast Model in vitro and Color Doppler Flow Imaging in vivo

Objective: The purpose of this study was to determine whether color Doppler sonogram can accurately depict the placental vascular structures using a latex cast model of the placental vessels, and to make a nomogram of several blood flow parameters according to the vascular structures.

Correlation of neuron-specific enolase and S100B with histological cerebral damage in fetal sheep after severe asphyxia

Experimental brain damage was induced in 16 fetal sheep by umbilical cord occlusion, and the correlation of neuron-specific enolase (NSE) or S100B with the damage grade was investigated in seven fetuses. Significant correlations of damage degree with NSE (p = 0.016) and S100B (p = 0.018) in serum 2 h after insult were shown by Spearmans test. These findings suggest that they represent potentially useful markers for detecting brain damage at early stage after ischemic insult.

Vaginal yolk sac (endodermal sinus) tumors in infancy presenting persistent vaginal bleeding.

Vaginal yolk sac (endodermal sinus) tumors were diagnosed in two girls (ages 12 and 46 months). In both, the only manifestation was persistent vaginal bleeding. Pelvic ultrasonography, computed tomography, and magnetic resonance imaging revealed solitary vaginal masses (diameter, 5 and 2 cm, respectively). Serum α‐fetoprotein was highly elevated in one patient and normal in the other. Biopsy was performed in the first patient, and a tumor excision, in the second. Combination chemotherapy with cisplatin, etoposide, and bleomycin or carboplatin was administered to the first patient, and shortly thereafter, the tumor size decreased by more than half; serum α‐fetoprotein was normalized after four chemotherapy cycles. After chemotherapy, magnetic resonance imaging revealed a small residual lesion, however the second biopsy revealed no viable tumor cells. In the second patient, no visible tumor was observed after chemotherapy by vaginoscopy. Both patients are well at 19 and 14 months after diagnosis, respectively.