Prenatal exposure to bisphenol-A is associated with Toll-like receptor-induced cytokine suppression in neonates.

BACKGROUND: Despite widespread human exposure to biphenol A (BPA), limited studies exist on the association of BPA with adverse health outcomes in young children. This study aims to investigate the effect of prenatal exposure to BPA on toll-like receptor-induced cytokine responses in neonates and its association with infectious diseases later in life. METHODS: Cord bloods were collected from 275 full-term neonates. Production of TNF-α, IL-6, and IL-10 were evaluated after stimulating mononuclear cells with toll-like receptor ligands (TLR1-4 and 7-8). Serum BPA concentrations were analyzed by enzyme-linked immunosorbent assay. Bacteria from nasopharyngeal specimens were identified with multiplex PCR and culture method. RESULT: Result showed significant association between cord BPA concentration and TLR3- and TLR4-stimulated TNF-α response (P = 0.001) and that of TLR78-stimulated IL-6 response (P = 0.03). Clinical analysis did not show prenatal BPA exposure to be correlated with infection or bacterial colonization during the first year of life. CONCLUSION: This is the first cohort study that indicated prenatal BPA exposure to play a part in TLR-related innate immune response of neonatal infants. However, despite an altered immune homeostasis, result did not show such exposure to be associated with increased risk of infection during early infancy.

Maternal Vitamin D Level Is Associated with Viral Toll-Like Receptor Triggered IL-10 Response but Not the Risk of Infectious Diseases in Infancy.

Reports on the effect of prenatal vitamin D status on fetal immune development and infectious diseases in childhood are limited. The aim of this study was to investigate the role of maternal and cord blood vitamin D level in TLR-related innate immunity and its effect on infectious outcome. Maternal and cord blood 25 (OH)D level were examined from 372 maternal-neonatal pairs and their correlation with TLR-triggered TNF-α, IL-6, and IL-10 response at birth was assessed. Clinical outcomes related to infection at 12 months of age were also evaluated. The result showed that 75% of the pregnant mothers and 75.8% of the neonates were vitamin deficient. There was a high correlation between maternal and cord 25(OH)D levels (r = 0.67, p < 0.001). Maternal vitamin D level was inversely correlated with IL-10 response to TLR3 (p = 0.004) and TLR7-8 stimulation (p = 0.006). However, none of the TLR-triggered cytokine productions were associated with cord 25(OH)D concentration. There was no relationship between maternal and cord blood vitamin D status with infectious diseases during infancy. In conclusion, our study had shown that maternal vitamin D, but not cord vitamin D level, was associated with viral TLR-triggered IL-10 response.

Paraurethral striated muscular structures and pelvic floor muscles contribute to resting urethral closure pressure in rats.

INTRODUCTION AND HYPOTHESIS: We investigated physiological functions of the extraordinary muscular structure in the paraurethral area with pelvic floor muscle and the impact of these muscular structures on the resting maximal urethral closure pressure (MUCP) in rats. METHODS: Sixteen female Wister rats were divided into four groups: Groups I and II rats received 5 and 2.5 IU botulinum toxin A (BoNT-A), respectively, injected into the bilateral paraurethral striated muscles. Group III rats received 2.5 IU BoNT-A injected into the bilateral pelvic floor muscles, and group IV rats received 2.5 IU BoNT-A injected into the unilateral pelvic floor muscles. Measurements of MUCP were made at different time points after BoNT-A injection. RESULTS: All groups showed a rapid reduction in average MUCP by 70-80 % after BoNT-A injection, regardless of injection site or side. CONCLUSIONS: Paraurethral striated muscular structures and the pelvic floor muscles possess the function of maintaining resting MUCP in rats.

The alteration of placental-derived soluble MHC class I chain-related protein A and B during pregnancy.

OBJECTIVE: According to a novel mechanism for fetal evasion from maternal immune attack via the engagement and down-regulation of the maternal natural killer cell receptor NKG2D by soluble MHC class I chain-related proteins (sMIC) A and B derived from placenta, we aimed to measure whether the sMICA/B level altered during pregnancy. DESIGN AND SETTING: Healthy women undergoing routine antepartum examination at Kee-Lung Chang Gung Memorial Hospital from December 2006 to December 2007 were prospectively registered for this study. SAMPLES: We collected 337 serum specimens and 10 amniotic fluid samples from 300 normal pregnant women for sMICA/B analysis. METHODS: Capture ELISA procedures were used to determine sMICA/B concentration in serum and amniotic fluid specimens. MAIN OUTCOME MEASURES: We hypothesized that the sMICA/B level would increase in proportion to the gestational age to protect the fetus from maternal immune rejection in the normal pregnancy. Results. The serum sMICA/B level rose gradually with the progression of gestation and decreased after the second trimester, with the lowest level appearing before delivery. In addition, we found that levels of soluble MICA/B were extremely low in amniotic fluid. CONCLUSIONS: We suggest that, as delivery approaches, the reduced production of soluble MICA/B by the aged placenta may be playing a role in parturition. Furthermore, we suggest that the effect of soluble MICA/B on natural killer cells of pregnant women is limited to the maternal placental surface, but not transferred through the placenta into the amniotic cavity.

Microencapsulated rhEGF to facilitate epithelial healing and prevent scar formation of cesarean wound: A randomized controlled trial.

OBJECTIVE: Cesarean section (CS) is a major surgical intervention that affects women at childbearing age. Scarring from CS potentially causes discomfort and psychological distress. Emerging evidence indicates that epidermal growth factor (EGF) plays crucial roles in wound healing with the potential of minimizing scar formation. This study aims to investigate the effect of microencapsulated recombinant human EGF (Me-EGF) in scar prevention. Silicone gel was incorporated as part of the routine scar treatment. MATERIALS AND METHODS: Healthy women scheduled for cesarean delivery were enrolled and randomized to three groups: (1) no scar treatment, (2) silicone gel only, or (3) silicone gel plus Me-EGF. Vancouver Scar Scale (VSS: vascularity, pigmentation, elasticity, and height) was used for scar assessment at the 6th month and 9th month after CS. RESULTS: A total of 60 women were enrolled, but one patient withdrew due to noncompliance with the follow-up visit requirement. Me-EGF-containing treatment group consistently scored the lowest on every parameter in the VSS scale, followed by silicone gel group, and the group with no scar treatment. Kruskal-Wallis tests indicated significant differences (p < 0.05) between Me-EGF-containing treatment group and the other two groups in vascularity, pigmentation, elasticity, and the VSS total score, at either 6th month, 9th month, or both time points. The only parameter not showing any significant between-group difference was scar height, but the pattern still remained the same, in which Me-EGF group scored better in both month 6 and 9. CONCLUSION: Surgical incisions in lower abdomen posed challenge in scar management. Our findings suggest that Me-EGF is a potential therapeutic option for better wound healing and scar prevention.

Extraordinary muscular structure leads to urethral injury after vaginal delivery in animal study.

INTRODUCTION AND HYPOTHESIS: The aim of this study is to explore causality of birth trauma after vaginal delivery and anatomical findings. METHODS: A total of 28 virgin mice were studied. Treatment groups received vaginal distention. Specimens were collected and subjected to the following fluorescence stains: progenitor cell (c-kit), smooth muscle (SMA), fibroblast (vimentin), and skeleton muscle (Masson's trichrome). Confocal microscopy was used to screen all of the urogenital tissue to localize the stained cells. RESULTS: Fibroblasts were spread all over perivaginal and urethral surroundings. Progenitor cells appeared at urethral-vagina intersection and urethral circle. They were noticeable only within smooth muscle layer. Two extraordinary skeleton muscle bands appeared on the urethra bilaterally. CONCLUSIONS: Our study demonstrates existence of muscle bands at the bilateral urethra. They can limit the mobility of urethra during vaginal delivery and thereby cause urethra injury. Progenitor cells are located only in the smooth muscle of the urethral circle.

Inhibitory effect of indigo naturalis on tumor necrosis factor-α-induced vascular cell adhesion molecule-1 expression in human umbilical vein endothelial cells.

The use of indigo naturalis to treat psoriasis has proved effective in our previous clinical studies. The present study was designed to examine the anti-inflammatory effect of indigo naturalis in primary cultured human umbilical vein endothelial cells (HUVECs). Pretreatment of cells with indigo naturalis extract attenuated TNF-α-induced increase in Jurkat T cell adhesion to HUVECs as well as decreased the protein and messenger (m)RNA expression levels of vascular cell adhesion molecule-1 (VCAM-1) on HUVECs. Indigo naturalis extract also inhibited the protein expression of activator protein-1 (AP-1)/c-Jun, a critical transcription factor for the activation of VCAM-1 gene expression. Since the reduction of lymphocyte adhesion to vascular cells by indigo naturalis extract could subsequently reduce the inflammatory reactions caused by lymphocyte infiltration in the epidermal layer and help to improve psoriasis, this study provides a potential mechanism for the anti-inflammatory therapeutic effect of indigo naturalis extract in psoriasis.

Improvement of overactive bladder symptoms: Is correction of the paravaginal defect in anterior vaginal wall prolapse necessary?

BACKGROUND: To explore the relationship between overactive bladder (OAB) symptoms and paravaginal defects (PVDs), and to identify the necessity of PVD repair by transvaginal mesh (TVM) for the treatment of OAB symptoms. METHODS: A retrospective clinical study of 30 women with advanced cystocele with limited apical and posterior vaginal wall prolapse was conducted to identify any changes in OAB symptoms following a single Perigee procedure. Prolapse was assessed using the pelvic organ prolapse quantification (POP-Q) system, and paravaginal defects were identified by sonography. Complete urodynamic examination was performed prior to and one year after operation. All patients completed the overactive bladder questionnaire pre- and postoperatively for a quantitative assessment of OAB symptoms. RESULTS: All patients showed a significant improvement at points Aa and Ba in the POP-Q system. The results of the administered questionnaire revealed statistically significant improvement postoperatively. The difference of OAB symptoms between the group with PVDs and that with central defects was not statistically significant (p = 0.67). Moreover, no statistically significant improvement of OAB symptoms in the group with repaired PVDs was observed postoperatively (p = 0.42). CONCLUSION: Statistical improvements of symptoms exist after Aa and Ba points recovery as evaluated by POP-Q system regardless of PVD existence identified by sonography. Repairing PVD did not show significantly improve the severity of OAB symptoms in objective urodynamic data or subjective questionnaire data. The superiority of TVM in PVD repair to manage OAB symptoms seems not manifest.

Exploring the dynamics of progenitor cells in the urethra after simulated birth trauma in mice.

OBJECTIVE: To examine the alteration in the cellular dynamics of the urethral tissue after a simulated birth trauma in a mouse model. MATERIALS AND METHODS: A total of 36 B6 mice received vaginal distention treatment, and four untreated mice were used as controls. Specimens were collected every 24 hours after the injury for 9 consecutive days and examined using immunofluorescent staining for cell markers including c-kit, smooth muscle actin (SMA), and vimentin. Confocal microscopy was used to localize the stained cells and determine the cell number. RESULTS: The number of c-kit positive cells increased after the 1st day and peaked on the 3rd day. The amount of SMA positive cells rapidly reduced to its lowest count on the 1st day and maintained a statistically significant low cell number than that at the basal level for 4 days after vaginal distension. The cell number finally returned to basal level on the 9th day. The amount of vimentin positive cells increased dramatically after the 1st day and plateaued from the 3rd day to the 9th day. The number of vimentin positive cells in the plateau phase was significantly higher than that of the control group. CONCLUSION: Our study confirmed that the dynamic change in different cell types after the urethral injury was dependent on the nature and physiology of the wound repairing cells during the tissue healing process. It might be a simple animal model to study birth trauma repair; however, the varied progenitor cell activity in different species should also be considered.

Detection of the subendometrial vascularization flow index by three-dimensional ultrasound may be useful for predicting the pregnancy rate for patients undergoing in vitro fertilization-embryo transfer.

OBJECTIVE: To obtain quantitative data on endometrial volume and subendometrial blood flow by three-dimensional ultrasound clue to endometrial receptivity. DESIGN: A prospective, nonrandomized clinical study. SETTING: One tertiary center for assisted reproduction. PATIENT(S): Fifty-four patients aged <38 years with normal basal serum FSH level experiencing their first IVF cycle, whose uteri were morphologically normal as confirmed by 3-dimensional (3-D) ultrasound, were studied. INTERVENTION(S): Ultrasound evaluation was performed for all patients with 3-D facility by a single operator on the day of hCG administration. MAIN OUTCOME MEASURE(S): Ultrasonographic parameters and conception rates. RESULT(S): Subendometrial vascularization flow index (VFI) in predicting the pregnancy rate of IVF was superior to that using vascularization index, flow index, or endometrial volume in the receiver operating characteristics curve analysis. The best prediction rate was achieved by a VFI cutoff value of >0.24. CONCLUSION(S): The detection of subendometrial blood flow by 3-D power Doppler ultrasound may be a useful ultrasound parameter in the prediction of pregnancy rate of IVF, especially subendometrial VFI.

Concentration of non-steroidal anti-inflammatory drugs in the pelvic floor muscles: an experimental comparative rat model.

PURPOSE: The aim of this study is to explore non-steroid anti-inflammation drugs (NSAIDs) potency for pelvic floor muscle pain by measuring local concentration in a rat model. MATERIALS AND METHODS: We used nine NSAIDs, including nabumetone, naproxen, ibuprofen, meloxicam, piroxicam, diclofenac potassium, etodolac, indomethacin, and sulindac, and 9 groups of female Wister rats. Each group of rats was fed with one kind of NSAID (2 mg/mL) for three consecutive days. Thereafter, one mL of blood and one gram of pelvic floor muscle were taken to measure drug pharmacokinetics, including partition coefficient, lipophilicity, elimination of half-life (T1/2) and muscle/plasma converting ratio (Css, muscle/Css, plasma). RESULTS: Diclofenac potassium had the lowest T1/2 and the highest mean Css, muscle/Css, plasma (1.9 hours and 0.85±0.53, respectively). The mean Css, muscle/Css, plasma of sulindac, naproxen and ibuprofen were lower than other experimental NSAIDs. CONCLUSION: Diclofenac potassium had the highest disposition in pelvic floor muscle in a rat model. The finding implies that diclofenac potassium might be the choice for pain relief in pelvic muscle.

Prospective assessment of overactive bladder symptoms in women who have undergone transvaginal surgery for advanced vaginal wall prolapse: a preliminary report.

AIM: To evaluate the changes in symptoms of overactive bladder (OAB) on the advanced cystocele after restoration of prolapse using the Perigee system. METHODS: This prospective clinical study recorded 16 women for the Perigee procedure due to advanced cystocele with OAB symptoms. Prolapse assessment was measured according to the pelvic organ prolapse quantization system. Complete urodynamic examination was performed before and six months after the operation. Subjects were also asked to fill in a questionnaire before and after the operation for a quantitative assay of OAB symptoms. Additional pelvic reconstructive surgeries including the Apogee procedure, retropubic tension-free vaginal tape and posterior colporrhaphy with tension-free vaginal tape were performed concurrently on 10 patients. RESULTS: Eleven cases were available for data analysis. Results showed significant improvement at points Aa and Ba after the operation. The Perigee procedure could restore the advanced cystocele adequately, with points Aa and Ba almost back to their normal physiological and anatomical positions. However, urodynamics showed two subjects with motor urgency and one with sensory urgency having objective improvement in urge sensation. Questionnaire results of postoperative subjective symptoms revealed a significant improvement with respect to coping, concern and sleep as compared to preoperative symptoms. CONCLUSION: This preliminary report reveals that the Perigee procedure is an efficient and effective surgical approach for the treatment of anterior vaginal wall prolapse. It can also improve the subjective symptoms of OAB.

Intrapartum spontaneous uterine rupture following uncomplicated resectoscopic treatment of Asherman's syndrome.

Since Asherman first published his series of intrauterine synechiae in 1948, only a few physicians have described the obstetric complications of patients who conceived following surgical treatment of intrauterine synechiae. We present a woman with a history of resectoscopic resection of intrauterine adhesions with a term pregnancy and spontaneous uterine rupture that occurred during the intrapartum period. At emergent cesarean section, hemoperitoneum of approximately 1500 mL was noted and a 10-cm defect was present in the lateral uterine wall; the edges of the defect were bleeding actively. Because of the potential for a disastrous outcome in the rupture of the pregnant uterus, patients treated for Asherman's syndrome should be identified early and appropriate precautions should be taken in their obstetric management.

Meigs' syndrome in a young woman with a normal serum CA-125 level.

We report on a 27-year-old woman who presented with an ovarian solid tumor (20 x 15 cm) and massive ascites. A physical examination and chest X-ray revealed a moderate amount of pleural effusion on the right side. Cytologic study of the pleural effusion showed reactive mesothelial cells without evidence of malignancy. Gram's stain was negative. The blood chemistry was within normal limits. The serum CA-125 level was 22 (normal, < 35) U/ml, the alpha-fetoprotein (AFP) level was 8 (normal, < 20) ng/ml, and the carcinoembryonic antigen (CEA) was 0.5 (normal, < 5) ng/ml. An explorative laparotomy revealed approximately 1500 ml of serous ascites and a very large multilobulated left adnexal mass (20 x 15 cm) with no malignant cytology in the ascitic fluid. Postoperatively, the pleural effusion spontaneously resolved, and the microscopic examination revealed a benign fibroma-thecoma, confirming the diagnosis of Meigs' syndrome. The symptoms resolved after removal of this pelvic tumor. This is an unusual case of a young female with Meigs' syndrome and a normal serum CA-125 level.

Ovarian endometrioma associated with very high serum CA-125 levels.

CA-125 is a 220-kD cell surface glycoprotein present in over 80% of non-mucinous epithelial ovarian carcinomas and it occurs in the serum of healthy males and females at low concentrations (< 35 U/mL). Serum CA-125 concentration may also be moderately elevated in several benign conditions, such as pelvic inflammatory disease, uterine fibroids, pregnancy, spontaneous abortion with chromosomal abnormality, and especially in endometriosis. However, serum CA-125 concentration is seldom > 100 IU/ml in endometriosis. In this paper, we present a patient with unilateral ovarian endometrioma associated with abnormally high serum CA-125 level (> 6000 U/mL) and after excision of the ovarian tumor, the CA-125 levels returned to normal. Our case further emphasizes the association of high levels of CA-125 with benign gynecologic conditions and we discussed the possible explanations for this abnormal elevation of CA-125 levels.

Severe ovarian hyperstimulation syndrome coexisting with a bilateral ectopic pregnancy.

Management of severe ovarian hyperstimulation syndrome (OHSS) includes hospitalization for fluid and electrolyte management. Abdominal paracentesis is also used as minimally invasive form of management in selected cases of severe OHSS following ovulation induction. However, if pregnancy ensues, the syndrome persists for a longer period, and the clinical manifestations of severe OHSS could mask the picture of a bleeding gestational sac. It could be easily overlooked unless the possibility of an ectopic pregnancy is kept in mind in cases of severe OHSS exacerbated by early pregnancy with or without a previous ectopic pregnancy history. We report a case of severe OHSS with simultaneous bilateral tubal pregnancy following intrauterine insemination (IUI). A 31-year-old woman with polycystic ovarian disease developed severe OHSS during the therapeutic course of IUI. An emergent exploratory laparotomy was performed 14 days after admission, and the operative findings showed persistent profuse bleeding from the bilateral fimbrial ends with marked enlargement of the ampullary portions. A linear salpingotomy was performed by a longitudinal incision along the area of maximal distension of the dilated fallopian tubes to preserve her fertility. We recommend that in cases of severe OHSS exacerbated by early pregnancy, serial serum beta-hCG and transvaginal ultrasound follow-up may be necessary due to the potential association of severe OHSS in pregnancy with an ectopic pregnancy.

Preliminary normal reference values of nuchal translucency thickness in Taiwanese fetuses at 11-14 weeks of gestation.

BACKGROUND: To investigate normal reference values of nuchal translucency (NT) thickness in normal Taiwanese fetuses between 11 and 14 weeks of gestation. METHODS: A prospective study of ultrasound measurements of fetal NT and crown-rump length (CRL) at 11-14 weeks of gestation was conducted in 724 consecutive Taiwanese fetuses between 1998 and 2001. The relationship between NT and 5-mm intervals of the CRL of the fetus was analyzed. NT thickness was converted into multiple of median (MoM) values for the proper CRL. The estimated risk of trisomy 21 was calculated in combination with maternal age and NT MoM. RESULTS: NT thickness increased with increasing CRL and gestational week in the first trimester. The mean (median) of NT thickness at 11-14 weeks was 1.56 (1.50) mm. Values of NT logMoM showed a normal Gaussian distribution with a mean of -0.0062 and standard deviation of 0.1146. The overall frequency of NT thickness of > 2.5 mm and > 3.0 mm was 1.7% (12/724) and 0.7% (5/724), respectively. There were 18 (2.5%) of 724 normal fetuses with the eseimated risk of trisomy 21, based on maternal age and NT thickness higher than 1:300. CONCLUSIONS: Because of weekly variations and racial differences in NT measurements, normal reference values should be established to convert NT thickness into MoM values for calculating the estimated risk of trisomy 21 in first-trimester NT screening.