Sang-Joon Choi

Effects of myricetin on the bioavailability of doxorubicin for oral drug delivery in Rats: Possible role of CYP3A4 and P-glycoprotein inhibition by myricetin

The purpose of this study was to investigate the effect of oral myricetin on the bioavailability and pharmacokinetics of orally and intravenously administered doxorubicin (DOX) in rats for oral delivery. The effect of myricetin on the P-glycoprotein (P-gp) and CYP3A4 activity was also evaluated. Myricetin inhibited CYP3A4 enzyme activity with 50% inhibition concentration of 7.8 μM. In addition, myricetin significantly enhanced the cellular accumulation of rhodamine 123 in MCF-7/ADR cells overexpressing P-gp. The pharmacokinetic parameters of DOX were determined in rats after oral (40 mg/kg) or intravenous (10 mg/kg) administration of DOX to rats in the presence and absence of myricetin (0.4, 2 or 10 mg/kg). Compared to the control group, myricetin significantly (p < 0.05, 2 mg/kg; p < 0.01, 10 mg/kg) increased the area under the plasma concentration-time curve (AUC, 51–117% greater) of oral DOX. Myricetin also significantly (p < 0.05, 2 mg/kg; p < 0.01, 10 mg/kg) increased the peak plasma concentration of DOX. Consequently, the absolute bioavailability of DOX was increased by myricetin compared to that in the control group, and the relative bioavailability of oral DOX was increased by 1.51- to 2.17-fold. The intravenous pharmacokinetics of DOX were not affected by the concurrent use of myricetin in contrast to the oral administration of DOX. Accordingly, the enhanced oral bioavailability in the presence of myricetin, while there was no significant change in the intravenous pharmacokinetics of DOX, could be mainly due to the increased intestinal absorption via P-gp inhibition by myricetin rather than to the reduced elimination of DOX. These results suggest that the increase in the oral bioavailability of DOX might be mainly attributed to enhanced absorption in the gastrointestinal tract via the inhibition of P-gp and to reduced first-pass metabolism of DOX due to inhibition of CYP3A in the small intestine and/or in the liver by myricetin.

P12.06: Indications for fetal echocardiography and diagnosis of congenital heart disease in Chosun University Hospital 1997 to 2008

first trimester. We aimed at describing key features of tetralogy of fallot (TOF) on real-time volumetric 3D reconstruction of fetal heart anatomy and Doppler angiography of great vessels at first trimester scan. Methods: In our center, second line ultrasound examinations of fetal heart is routinely offered at first trimester in all patients with a NT measurement > 99th centile. In cases with a diagnosis of TOF 3D volumes were retrospectively reviewed in order to define key features of this defect at first trimester. Results: During the study period, 3 cases of TOF was suspected and later confirmed. Fetal karyotype was performed allowing for the diagnosis of aneuploidy in all 3 cases. TOP was performed according to parents decision and local laws and pathological examination confirmed the diagnosis all 3 cases. 3 D volumes analysis allowed to pick up two major findings as early as first trimester. The axis of the heart which is in a left lateral deviation and abnormal three vessels view with a large aortic root and a small pulmonary artery. Conclusions: Our findings suggest that TOF might be suspected as early as first trimester in the presence of a left lateral deviation and abnormal three vessels view showing a large aortic root and a small pulmonary artery. Although these early cases seem to carry a very poor prognosis, sonographer should not overlook those signs, particularly when scanning fetuses with increased NT.

P02.80: Prenatal diagnosis of VACTERL association

gestation. Postnatal evaluation confirmed: V lumbar hemivertebrae; A imperforate anus and rectovaginal fistula; C subaortic IVC; TE esophagic atresia with tracheo esophagic fistula; R Hydronephrosis L unilateral talus. Comment: Between Nov 1998 and March 2006 in our institution, this is the first case of VACTERL syndrome presented in 43 000 deliveries. The diagnosis was suspected when an association of anomalies was found in a comprehensive ultrasound; despite that the urological condition was different from the prenatal diagnosis. This case confirms the need of a thorough evaluation of the fetal anomaly as soon as one anomaly has been found.

OP11.14: Ultrasonographic evaluation of the postpartum hemorrhage

compared between patients who delivered preterm with those who delivered at term. Statistical analysis was performed with SPSS package. Multiple logistic regression analysis was performed in order to identify the independent risk factors for preterm delivery. Results: A total of 87 women were enrolled in the study group; 26 patients (30.2%) had preterm delivery. When comparing patients who delivered preterm with those delivered at term, no differences were found in maternal characteristics (maternal age, parity, BMI and smoking) between the groups. The cerclage rate was not statistically significant between the groups (3.3% vs.3.8%, p = 0.905). Cesarean section rate was statistically significant higher among the PTD group (20.8% vs. 73.9%, p < 0.001). Cervical length ≤ 25 mm was to be independent risk factors for preterm delivery with OR-9.7, 95% CI 1.57–60, P = 0.014 (Table). Conclusion: Cervical length ≤ 25 mm among patients with vaginal bleeding at 22–34 weeks, is an independent risk factor for preterm delivery.

OP02.36: Combined anomalies in the fetuses with renal dysplasia

Objective: Renal tubular dysgenesis (RTD) is a lethal, irreversible renal abnormality presenting as severe oligohydramnios in mid second trimester. Cases can have autosomal recessive inheritance or are acquired. We describe prenatal findings in 3 cases detected by us and review the literature for diagnostic features. Methods: IRB approved review of records for histologically proven RTD cases. Literature review. Results: We managed three fetuses with proven RTD: 2 sibs and 1 sporadic. Pregnancies were otherwise unremarkable. All were singleton. There was no history of hypoxia or teratogen exposure including angiotensin converting enzyme (ACE) inhibitors. All had normal ultrasound examinations at 17–25 weeks but developed severe second-trimester oligohydramnios (23–26 wks). At onset, kidneys appeared normal or showed slight echogenic enlargement. All had cranial bone hypoplasia and wide sutures (hypocalvaria) confirmed by postnatal X-ray. One had echogenic bowel confirmed on X-ray and autopsy. Literature review revealed about 60 similar cases since 1983. Oligohydramnios was detected at 19 to 34 wk gestation. Hypocalvaria was recognized whenever sought. Most had findings of Potter sequence. Additional features included: previously affected sib, hypoxic and twinning complications and maternal hypertension treated with ACE inhibitors. All liveborns had profound renal failure and died at or shortly after birth. Histologically, the kidneys show characteristic absence of proximal convoluted tubules. Conclusions: Lethal fetal RTD may be suspected in fetuses with second-trimester onset of unexplained severe oligohydramnios who show normal size kidneys and hypocalvaria. Supporting features include history of an affected sib, and conditions which decrease renal blood flow such as fetal hypoxia, twinning complications, or maternal ACE inhibitor exposure. The recent delineation of associated genes may enable early prenatal diagnosis in at risk couples.

P14.80: Prenatal ultrasound detection of pancreatic cyst at 30 weeks' gestation

The first report of prenatal diagnosis of Nonne-Milroy lymphedema was documented in 2001 and up to date only 7 cases have been described including our two cases. We report on two consecutive pregnancies with increased nuchal skin fold with normal outcome. We will also review all the cases diagnosed in the antenatal period and the variable phenotypic expression of this condition. Increased nuchal translucency or nuchal skin fold with normal karyotype has been appropriately named a ‘‘pain in the neck’’ because it casts a shadow over a fetus’s outcome and creates a lot of angst for the parents. Nonne-Milroy lymphedema is associated with both increased nuchal translucency and – skin fold and variable degrees of generalised edema with marked pedal edema. It has an autosomal dominant inheritance pattern and the prognosis is usually good. Our patient is a 31yrs G2P1 known to this unit in a previous pregnancy with increased nuchal skinfold with normal karyotype. That child is now 4 years and doing well with moderate pedal edema and Nonne-Milroy lympedema diagnosed. The patient presented to us in the second trimester of her subsequent pregnancy with an increased nuchal skinfold and mild hydrops (pleural effusions, ascites and scalp edema). The parents declined invasive testing in view of the known excellent prognosis. The pregnancy was uneventful with no additional findings during the pregnancy. Our case and the reviewed cases highlight that careful examination of a fetus and taking a family history can refine the diagnosis to allow for appropriate counselling. Nonne-Milroy lympedema is a single gene disorder with a known gene locus on the long arm of chromosome 5 and prenatal diagnosis can be offered to the parents if it supports the decision making process. It also emphasises the importance of keeping genetic samples for father testings since most patients will be offered an invasive test to assess the fetal karyotype.

P14.14: The effects of transabdominal amnioinfusion to severe midtrimester oligohydramnios with intact membrane

Results: Between Dec. 30, 2003 and Feb. 4, 2004, we studied 92 women. Median maternal age was 32.3 years; median gestational age 19.2 weeks (17.6–23.9); median body mass index (BMI) 22.5 (15.0–40.9); 69 women (75%) used skin cream; 15 (16%) had lower abdominal surgery; and 74 (80%) were ‘‘white’’. The average US score was 2.4. There was substantial agreement between the two readers (ICC = 0.75). In univariate analyses, US score was associated negatively with BMI (rank correlation = −0.6; p < 0.0001) and previous surgery (P = 0.03) and positively with skin cream use (P = 0.004). In multiple regression analysis, statistically significantly higher US scores were seen with low BMI (p < 0.01); and ‘‘white’’ ethnicity (P = 0.02). Skin cream use, previous surgery and gestational age were not significant predictors of US score. Those with lower BMI were more likely to use creams. Conclusions: BMI and ethnicity were significant predictors of US image quality score. Adjusting for BMI, skin creams did not appear to significantly affect US quality.