Takuji Tomimatsu

Reliable predictors of neonatal immune thrombocytopenia in pregnant women with idiopathic thrombocytopenic purpura

Of infants born to women with idiopathic thrombocytopenic purpura (ITP), about 10–15% have transient neonatal immune thrombocytopenic purpura (NITP). Of concern is the lack of a reliable predictor for NITP. We conducted a retrospective study of all pregnancies with ITP at Osaka University Hospital over the past 16 years analyzing a total of 127 pregnancies in 88 women with ITP to assess the predictive value of various clinical factors regarding neonatal platelet count in the current pregnancy. We also reviewed the literature concerning ITP in pregnancy and NITP prediction. Neonatal platelet counts were less than 100 × 109/L in 20 of 130 neonates (15.4%), less than 50 × 109/L in 11 neonates (8.5%), and less than 20 × 109/L in three neonates (2.3%). There was a strong correlation between the first and second sibling regarding the occurrence and the severity of NITP with Spearman correlation coefficient of 0.55 (P = 0.001) at birth and 0.63 (P < 0.0001) at nadir after birth. A maternal platelet count less than 100 × 109/L at delivery showed a statistical trend for an association with the occurrence of NITP (P = 0.043). Moreover, maternal ITP refractory to splenectomy correlated with a higher risk for fetal or neonatal ICH according to the review of the literature. In conclusion, pregnant women who have had a previous offspring with NITP or who have ITP refractory to splenectomy may be at particular risk of delivering an offspring with significant NITP. Management decisions, including mode of delivery, may be altered by the degree of risk for potentially severe NITP. Am. J. Hematol., 2012.

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.

Central aortic blood pressure and augmentation index during normal pregnancy

The current study tested the hypothesis that pregnancy-related changes are more pronounced in central hemodynamics, and both central aortic systolic blood pressure (cSBP) and augmentation index (AIx) are independent from brachial systolic blood pressure (bSBP) in normal pregnant subjects. In 830 healthy pregnant women from 12 to 36 weeks gestation, we measured cSBP and AIx-75 (AIx at heart rate of 75 beats per minute) non-invasively by pulse waveforms of the radial artery using an automated applanation tonometric system. In 69 pregnant women, we recorded these data longitudinally. cSBP and AIx-75 significantly declined during pregnancy, reaching its nadir in mid-pregnancy and rising towards term. Pregnancy-related changes were more pronounced in AIx-75 compared with cSBP, but less evident in bSBP. AIx-75, but not cSBP, was independent from bSBP throughout pregnancy. cSBP and AIx-75, but not bSBP, were significantly increased in healthy pregnant women older than 35 years. This study established normal values for pulse wave analysis parameters throughout pregnancy, and indicated that pulse wave analysis might offer additional and independent information about maternal arterial compliance to conventional brachial blood pressure measurements. These data may be used as the basis for further investigation into the role of pulse wave analysis in the assessment, management and prediction of disorders, which might interfere with pregnancy-related cardiovascular adaptations.

Nicotine restores endothelial dysfunction caused by excess sFlt1 and sEng in an in vitro model of preeclamptic vascular endothelium: a possible therapeutic role of nicotinic acetylcholine receptor (nAChR) agonists for preeclampsia.

OBJECTIVE In this study we tested the hypothesis that nicotine restores proangiogenic functions to endothelial cells pretreated with soluble fms-like tyrosine kinase 1 and/or soluble endoglin. STUDY DESIGN Wound healing assay and tube formation assay were performed using human umbilical vein endothelial cells treated with nicotine (10(-9) to 10(-6) M), and with various combinations of soluble fms-like tyrosine kinase 1 (100 ng/mL), soluble endoglin (100 ng/mL), and nicotine (10(-7) M). Enzyme-linked immunosorbent assay was performed to measure vascular endothelial growth factor, placental growth factor, and transforming growth factor-beta1 concentrations in the conditioned media treated with nicotine (10(-9) to 10(-6) M). RESULTS Nicotine significantly facilitated endothelial migration and tube formation. By contrast, soluble fms-like tyrosine kinase 1 and/or soluble endoglin suppressed these endothelial functions. Nicotine restored these soluble fms-like tyrosine kinase 1 and/or soluble endoglin-reduced endothelial functions. Placental growth factor, but not transforming growth factor-beta1, production was significantly stimulated by the presence of nicotine. Vascular endothelial growth factor was undetectable. CONCLUSION Our results suggest a possible mechanism for the protective effects of cigarette smoking against preeclampsia, thus proposing a therapeutic potential of nicotine or other nicotinic acetylcholine receptor agonists for preeclampsia.

Spinal subarachnoid hematoma following spinal anesthesia in a patient with HELLP syndrome

A case of subarachnoid hematoma following spinal anesthesia for cesarean section in a patient with HELLP syndrome is reported. A 39-year-old woman underwent cesarean section under spinal anesthesia for worsening preeclampsia with HELLP syndrome. Despite full recovery from the spinal anesthetic, on the second postoperative day she felt numbness on the posterior aspect of her right leg, noticed she was insensitive to bladder fullness and had mild flaccid paraparesis. Magnetic resonance imaging revealed a spinal subarachnoid hematoma with cauda equina compression. With conservative management she made an almost complete recovery within three months. Serial magnetic resonance imaging showed spontaneous regression of the hematoma. The risk of spinal subarachnoid hematoma following obstetric regional anesthesia is exceedingly small even in a patient with coagulopathy and, to our knowledge, this is only the second reported case following obstetric regional anesthesia. Anesthesia for HELLP syndrome in patients with an adequate platelet count but without disseminated intravascular coagulation is controversial. It is therefore important for clinicians to recognize the symptoms and signs of spinal subarachnoid hematoma to avoid delay in treatment that might result in severe neurological deficit.

Balloon tamponade during cesarean section is useful for severe post-partum hemorrhage due to placenta previa

Aim:  Severe post‐partum hemorrhage during cesarean section due to placenta previa is still one of the leading causes of maternal mortality. The aim of this study was to evaluate the efficiency of intrauterine tamponade with a Sengstaken‐Blakemore tube (SB‐tube) for the treatment of severe post‐partum hemorrhage in cases of placenta previa.

Oxidative stress-induced S100B protein from placenta and amnion affects soluble Endoglin release from endothelial cells.

Oxidative stress with elevated intracellular Ca(2+) concentration as well as endothelial dysfunction is a component of pre-eclampsia. Our aim was to investigate the oxidative stress-dependent expression of Endoglin and Ca(2+)-binding S100B protein from villous and amniotic tissue cultures, and to assess sEng expression from S100B protein-stimulated endothelial cells. We initially examined Endoglin and Hydroxy-nonenal-(HNE)-modified proteins in the placentas and amnion obtained from women with pre-eclampsia (n = 8), and healthy controls (n = 8) by immunohistochemistry. To examine oxidative stress and the S100B protein effect on sEng expression from endothelial cells, normal villous and amniotic tissue cultures were stimulated by 4-HNE, sodium fluoride and xanthine/xanthine oxidase, whereas human umbilical vein endothelial cell cultures were treated with S100B protein in a dose- and time-dependent manner at 37 degrees C in an environment of 95% air and 5% of CO(2). Culture supernatants were assessed using ELISA. Cell viability was determined using MTS assay. The concentrations of sEng and S100B protein were significantly increased in the villous and amniotic tissue culture supernatants under oxidative stress. S100B protein-stimulated endothelial cells released sEng into conditioned media with a significantly higher expression levels at a concentration of 200 pM-20 nM S100B by 2 h, whereas treated with 200 nM of S100B endothelial cells significantly expressed sEng by 12 h and stimulated the cell proliferation by the same period of time. Our findings show that oxidative stress affects sEng and S100B protein expression from villous and amniotic tissues, and picomolar and low nanomolar concentrations of S100B protein significantly up-regulate sEng release from endothelial cells leading to endothelial dysfunction.

Ceftriaxone preconditioning confers neuroprotection in neonatal rats through glutamate transporter 1 upregulation.

Objective: This study investigated the hypothesis that ceftriaxone preconditioning ameliorates brain damage in neonatal animals through glutamate transporter 1 (GLT-1) upregulation. Study design: Sprague Dawley rats were pretreated with ceftriaxone, erythromycin, minocycline, or saline for 5 consecutive days starting from postnatal day 2 (P2), and GLT-1/glutamate-aspartate transporter (GLAST) messenger RNA (mRNA) and protein levels were examined in the P7 brains. After ceftriaxone or saline preconditioning, the P7 rats underwent hypoxic-ischemic (H-I) procedure or sham operation. One week after the procedure (P14), hematoxylin-eosin staining, microtubule-associated protein 2 (MAP-2) immunostaining, and transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) assay were used to examine neuronal damage and possible neurotoxicity. Results: Repeated ceftriaxone injections significantly increased GLT-1 mRNA and protein levels but not GLAST. Following such treatment and H-I procedure, the MAP-2-positive area increased and TUNEL-positive cells decreased. Conclusion: Antenatal ceftriaxone may help to provide neuroprotection in the immature brain and become a new prophylactic strategy to reduce neonatal encephalopathy in clinical perinatal medicine.

Postischemic Hyperthermia Induced Caspase-3 Activation in the Newborn Rat Brain after Hypoxia-Ischemia and Exacerbated the Brain Damage

The effects of postischemic hyperthermia were investigated in the newborn rat brain after hypoxia-ischemia (HI). Seven-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 30 min, and divided into a hyperthermia group (rectal temperature at 39°C for 6 h) and a normothermia group. Hyperthermia resulted in an approximately 5-fold increase in activated caspase-3 24 h after HI when compared with the normothermia group, and gross loss of brain tissue was observed only in the hyperthermia group at 7 and 30 days after HI. Our results show that postischemic hyperthermia exacerbates HI injury in immature brains, and that the mechanism is strongly associated with activation of an apoptotic pathway.

Umbilical Cord Ulcer Associated with Fetal Jejunal Atresia: Report of 2 Cases

We report 2 cases of umbilical cord ulcer associated with fetal jejunal atresia. Both of them developed a severe intrauterine hemorrhage, followed by fetal heart rate decelerations, and underwent emergency cesarean section. Bloody amniotic fluid and umbilical cord ulcers were observed in both cases. Although both cases were successfully resuscitated, neurological impairment and renal failure developed in 1 case due to prolonged asphyxia. In a review of the literature, umbilical cord ulcer was associated only with congenital duodenal atresia or jejunal atresia, but not with ileal atresia. Although the prenatal diagnosis of duodenal or upper jejunal atresia has been established, the prenatal diagnosis of this complication has not been reported. In such cases, detailed examination of the umbilical cord by ultrasonography may be useful for the prenatal diagnosis of this disease.