Koichiro Shimoya

Post-ischemic hypothermia reduced IL-18 expression and suppressed microglial activation in the immature brain

Inflammation is an important factor for hypoxia-ischemia (HI) brain injury. Interleukin (IL)-18 is a proinflammatory cytokine which may be a contributor to injury in the immature brain after HI. To investigate the effects of post-HI hypothermia on IL-18 in the developing brain, 7-day-old rats were subjected to left carotid artery ligation followed by 8% oxygen for 60 min and divided into a hypothermia group (rectal temperature 32 degrees C for 24 h) and a normothermia group (36 degrees C for 24 h). The IL-18 mRNA was analyzed with real-time RT-PCR, and the protein level was analyzed by Western blot, and the location and source of IL-18 were assessed by immunohistochemistry. The significant increase of the IL-18 mRNA was observed in the ipsilateral hemispheres of the normothermia group at 24 h and 72 h after HI compared with controls, but the level in the ipsilateral hemispheres of the hypothermia group was significantly reduced at both time points, compared with the normothermia group, respectively. The IL-18 protein level in the ipsilateral hemispheres of the normothermia group significantly increased at 72 h after HI compared with controls, however, the protein level of the hypothermia group was significantly decreased, compared with the normothermia group. IL-18-positive cells were observed throughout the entire cortex, corpus callosum (CC) and striatum in the ipsilateral hemispheres of normothermia group at 72 h after HI, however, little positive cells were observed in the hypothermia group. Double labeling immunostaining found that most of the IL-18-positive cells were colocalized with lectin, which is a marker of microglia. The number of ameboid microglia (AM) in the normothermia group was significantly increased in cortex and CC, compared with the number in controls, but there were very few ramified microglia (RM) in these areas. In contrast, the number of AM in the hypothermia group was significantly decreased in cortex and CC, compared with the number in the normothermia group, and there were no significant differences in the number of AM and RM between the hypothermia group and controls. In conclusion, we found that IL-18 mRNA and the protein level were attenuated by post-HI hypothermia and that post-HI hypothermia may decrease microglia activation in the developing brain.

Use of uterine fundal pressure maneuver at vaginal delivery and risk of severe perineal laceration

ObjectiveOwing to the lack of evidence supporting the use of uterine fundal pressure maneuver in vaginal delivery, the role of the maneuver is undetermined and remains controversial. The aim of this study was to identify the prone factor of the use of uterine fundal pressure maneuver and to evaluate its obstetrical outcomes.MethodsAll vaginal delivery records between 1 January 2005 and 30 April 2006 were evaluated. Maternal and neonatal variables and obstetrical complications were analyzed for subjects underwent uterine fundal pressure maneuver.ResultsSix hundred sixty-one vaginal deliveries were evaluated. Fundal pressure maneuver was performed in 39 cases (5.9%, 95% CI 4.4–7.1). Primiparity (76.9 vs. 53.3%; odds ratio 2.92, 95% CI 1.36–6.25, Pxa0=xa00.004), larger maternal body weight gain during pregnancy (11.16xa0±xa00.4xa0kg vs. 10.05xa0±xa00.16xa0kg, Pxa0=xa00.013), and longer duration of labor (922.3xa0±xa0111.7 vs. 566.6xa0±xa018.3xa0min, Pxa0=xa00.003) were prone risk factors for the use of uterine fundal pressure maneuver at vaginal delivery. One case of shoulder dystocia following uterine fundal pressure maneuver was reported (2.5 vs. 0%). Episiotomy (76.9 vs. 44.9%, Pxa0<xa00.001) and vacuum extraction (41.0 vs. 3.8%, Pxa0<xa00.001) were frequently performed with uterine fundal pressure maneuver. Uterine fundal pressure maneuver increased the risk of severe perineal laceration (28.1 vs. 4.8%; odds ratio 2.71, 95% CI 1.03–7.15, Pxa0=xa00.045). The risk of severe perineal laceration was synergistically increased with the concurrent use of uterine fundal pressure maneuver with vacuum extraction and episiotomy.ConclusionUterine fundal pressure maneuver during the second stage of labor increased the risk of severe perineal laceration. The use of the maneuver must be cautioned and careful attention must be paid to its application.

Significance of histologic pattern of carcinoma and sarcoma components on survival outcomes of uterine carcinosarcoma

BACKGROUNDnTo examine the effect of the histology of carcinoma and sarcoma components on survival outcome of uterine carcinosarcoma.nnnPATIENTS AND METHODSnA multicenter retrospective study was conducted to examine uterine carcinosarcoma cases that underwent primary surgical staging. Archived slides were examined and histologic patterns were grouped based on carcinoma (low-grade versus high-grade) and sarcoma (homologous versus heterologous) components, correlating to clinico-pathological demographics and outcomes.nnnRESULTSnAmong 1192 cases identified, 906 cases were evaluated for histologic patterns (carcinoma/sarcoma) with high-grade/homologous (40.8%) being the most common type followed by high-grade/heterologous (30.9%), low-grade/homologous (18.0%), and low-grade/heterologous (10.3%). On multivariate analysis, high-grade/heterologous (5-year rate, 34.0%, P = 0.024) and high-grade/homologous (45.8%, P = 0.017) but not low-grade/heterologous (50.6%, P = 0.089) were independently associated with decreased progression-free survival (PFS) compared with low-grade/homologous (60.3%). In addition, older age, residual disease at surgery, large tumor, sarcoma dominance, deep myometrial invasion, lymphovascular space invasion, and advanced-stage disease were independently associated with decreased PFS (all, P < 0.01). Both postoperative chemotherapy (5-year rates, 48.6% versus 39.0%, P < 0.001) and radiotherapy (50.1% versus 44.1%, P = 0.007) were significantly associated with improved PFS in univariate analysis. However, on multivariate analysis, only postoperative chemotherapy remained an independent predictor for improved PFS [hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.27-0.43, P < 0.001]. On univariate analysis, significant treatment benefits for PFS were seen with ifosfamide for low-grade carcinoma (82.0% versus 49.8%, P = 0.001), platinum for high-grade carcinoma (46.9% versus 32.4%, P = 0.034) and homologous sarcoma (53.1% versus 38.2%, P = 0.017), and anthracycline for heterologous sarcoma (66.2% versus 39.3%, P = 0.005). Conversely, platinum, taxane, and anthracycline for low-grade carcinoma, and anthracycline for homologous sarcoma had no effect on PFS compared with non-chemotherapy group (all, P > 0.05). On multivariate analysis, ifosfamide for low-grade/homologous (HR 0.21, 95% CI 0.07-0.63, P = 0.005), platinum for high-grade/homologous (HR 0.36, 95% CI 0.22-0.60, P < 0.001), and anthracycline for high-grade/heterologous (HR 0.30, 95% CI 0.14-0.62, P = 0.001) remained independent predictors for improved PFS. Analyses of 1096 metastatic sites showed that carcinoma components tended to spread lymphatically, while sarcoma components tended to spread loco-regionally (P < 0.001).nnnCONCLUSIONnCharacterization of histologic pattern provides valuable information in the management of uterine carcinosarcoma.

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.

Change of salivary stress marker concentrations during pregnancy: Maternal depressive status suppress changes of those levels

Aim:u2002 The aim of the present study was to show changes in salivary cortisol and chromogranin A/protein concentrations as stress markers during pregnancy and to clarify the effect of chronic stress on stress markers.

Association Between Sexual Health and Delivery Mode

Introduction Female sexual function changes considerably during pregnancy and the postpartum period. In addition, womens physical and mental health, endocrine secretion, and internal and external genitalia vary during these times. However, there are limited studies on the relationship between delivery and sexual function. Aim The present study aimed to demonstrate the association between sexual function and delivery mode. Methods Mothers who delivered a single baby at term were recruited for the study, and 435 mothers were analyzed. Main Outcome Measures The Female Sexual Function Questionnaire (SFQ28) scores and mothers backgrounds were assessed at 6 months after delivery. Results The delivery mode affected the SFQ28 partner domain. Episiotomy affected the arousal (sensation) domain. Multiple regression analysis revealed that maternal age and cesarean section were significantly associated with several SHQ28 domains. Conclusion This study suggests that routine episiotomies at delivery should be avoided to improve postpartum maternal sexual function. Maternal age and cesarean section were found to affect postpartum sexual health.

Is 38 weeks late enough for elective cesarean delivery

L1 and L2 compression fractures. the γ-globulin region that was identified as an IgGλ protein by immunoelectrophoresis. Bone marrow examination showed a remarkable increase in the number of plasma cells (50%). Serum β-microglobulin level was increased to 4.68 mg/L. The patient was diagnosed with multiple myeloma stage IIIa. Two weeks after surgery the patient began chemotherapy with 2 cycles of vincristine, doxorubicin (Adriamycin; Pfizer, New York, NY, USA), and dexamethasone. This caused leucopenia and general weakness; it was replaced by a secondary therapy with bortezomib (Velcade; JanssenCilag, High Wycombe, UK), thalidomide, and dexamethasone. The patient responded well with no aggravating signs of multiple myeloma. The prognosis for women with multiple myeloma is poor, with a relative survival rate of 25% and 9% for 5 and 10 years, respectively [2]. The offspring of patients appear to be unaffected by the maternal disease [3].

Maternal Blood Serum and Plasma Human Tumor-Associated Antigen RCAS1 During the Course of Uncomplicated Pregnancies: A Prospective Study

Citation Tskitishvili E, Sharentuya N, Tsubouchi H, Kinugasa‐Taniguchi Y, Kanagawa T, Shimoya K, Tomimatsu T, Kimura T. Maternal blood serum and plasma human tumor‐associated antigen RCAS1 during the course of uncomplicated pregnancies: a prospective study. Am J Reprod Immunol 2010; 64: 218–224

The effect of tumor-associated protein RCAS1 gene silencing on blood pressure and urinary protein excretion in pregnant mouse: a pilot study.

OBJECTIVEnThe level of tumor-associated receptor-binding cancer antigen that is expressed on SiSo cells (RCAS1) is decreased significantly in preeclamptic pregnancies. We hypothesized that RCAS1 protein gene silencing might affect blood pressure and proteinuria in pregnant mice.nnnSTUDY DESIGNnOn postcoital day 7.5, pregnant imprinting control region mice were subjected to the transfer of small interfering RNA (siRNA) against RCAS1 protein into the uterine cavity with the use of a hemagglutinating virus Japan envelope. Scramble siRNA was used as a negative control. Blood pressure and urine albumin/creatinine measurements were performed. The effect of the transferred siRNA was examined in uterine samples on postcoital day 8.5 with the use of Western blotting and immunohistochemistry analyses.nnnRESULTSnIn the RCAS1 siRNA group, blood pressure significantly raised on postcoital days 9.5, 10.5, 11.5, and 15.5, whereas urine albumin/creatinine ratio was significantly increased on postcoital day 9.5nnnCONCLUSIONnOur results suggest the importance of RCAS1 protein in the pathophysiologic condition of preeclampsia.

Effects of 4-Hydroxy-2-Nonenal, a Major Lipid Peroxidation-Derived Aldehyde, and N-Acetylcysteine on the Cyclooxygenase-2 Expression in Human Uterine Myometrium

Background: Chorioamnionitis is one of the important causes of preterm labor. Preterm labor with chorioamnionitis is associated with oxidative stress. We reported that 4-hydroxy-2-nonenal (4-HNE), a major end product of oxidative fatty acid metabolism, is accumulated in the placenta with chorioamnionitis. The aim of this study was to confirm the effect of 4-HNE on cyclooxygenase-2 (COX-2) and prostaglandin (PG) induction in the uterine myometrial tissues. We also examined the effect of N-acetylcysteine (NAC) on 4-HNE-induced COX-2 expression. Methods: Uterine myometrial tissues were obtained from 5 patients. One of them underwent elective cesarean section without labor, and 4 of them underwent hysterectomy because of placental previa or atonic bleeding. We stimulated the uterine myometrial tissues with 4-HNE. In addition, the tissues were pretreated with NAC before 4-HNE treatment. The expression of COX-2 mRNA was observed by real-time PCR. PGE2 and prostacyclin release into the supernatants of the tissue cultures was measured by ELISA. Results: 4-HNE induced the COX-2 mRNA expression and PGE2 production in the uterine myometrial tissue culture in a dose-dependent and time-dependent manner. NAC inhibited 4-HNE-induced COX-2 expression. Conclusion: 4-HNE may play an important role in preterm labor. NAC might be protective against preterm labor under oxidative stress.