The metabolism and transplacental transfer of oseltamivir in the ex vivo human model.

Unlabelled: Oseltamivir phosphate is extensively metabolized in the ex vivo human placenta model, and the transplacental passage of the metabolite oseltamivir carboxylate is incomplete.

Objective: To evaluate the metabolism and transplacental transfer of oseltamivir (Tamiflu) in the ex vivo human placental model.

Study Design: Perfusion studies were performed in six placentas from term, uncomplicated deliveries.

Unilateral twin ectopic pregnancy in a patient with a history of multiple sexually transmitted infections.

Background: The incidence of unilateral twin ectopic pregnancy is a rare condition. Several factors increase the risk of ectopic pregnancy, the most important of which is pelvic inflammatory disease, followed by operative trauma, congenital anomalies, tumors, and adhesions resulting in anatomically distorted fallopian tubes. We present a case of a woman with a history of four confirmed sexually transmitted infections (STIs) including Chlamydia trachomatis, Neisseria gonorrhoeae, herpes simplex virus 2, and Treponema pallidum.

Divergent activities of an engineered antibody in murine and human systems have implications for therapeutic antibodies.

The MHC class I-related receptor, neonatal Fc receptor (FcRn), plays a central role in regulating the transport and in vivo persistence of immunoglobulin G (IgG). IgG-FcRn interactions can be targeted for engineering to modulate the in vivo longevity and transport of an antibody, and this has implications for the successful application of therapeutic IgGs. Although mice are widely used to preclinically test antibodies, human and mouse FcRn have significant differences in binding specificity.

Placental transfer of rosiglitazone in the ex vivo human perfusion model.

Objective: The objective of the study was to determine transplacental passage of rosiglitazone (Avandia) using the ex vivo human placental model.

Study Design: Perfusion studies were performed on 10 placentas from term, uncomplicated deliveries. Concentrations typical for an 8-mg oral dose (216 to 692 ng/mL) as well as 2- to 3-fold increased concentrations were tested (734 to 1261 ng/mL).

Transfer of meropenem in the ex vivo human placenta perfusion model.

Objectives: To determine maternal-fetal transplacental passage of meropenem in the ex vivo human perfusion model.

Study Design: Term placentae (n = 6) were collected immediately after delivery. A single cotyledon was localized, perfused and stabilized with physiologic Eagles minimal essential medium containing 3% bovine albumin and heparin as described by Chalier (Chalier JC.

Transplacental passage of vancomycin in the ex vivo human perfusion model.

Objectives: To determine maternal-fetal transplacental passage of vancomycin in the ex vivo human placental perfusion model.

Methods: Six term placentas were collected immediately after delivery and perfused with physiologic medium using the single cotyledon perfusion system. Vancomycin was added to the maternal medium and perfused through the maternal circulation of the cotyledon.

Ex vivo human placental transfer of the peptides pramlintide and exenatide (synthetic exendin-4).

Two peptides, pramlintide (37 amino acids), an analog of human amylin, and exenatide, synthetic exendin-4 (39 amino acids), are both in late-stage clinical development as potential new treatments for people with diabetes. Both are potential long-term treatments, and there is the likelihood that some women will become pregnant while using one of these peptide therapies. Therefore, it was important to evaluate the potential for each peptide to cross the placental barrier and thereby result in exposure to the fetus.

Transfer of inflammatory cytokines across the placenta.

Objective: The purpose of this study was to determine whether the placental transfer of interleukin (IL)-1alpha, IL-6, and tumor necrosis factor-alpha (TNF-alpha) occurs.

Methods: Four normal-term placentas were perfused for maternal-fetal transfer of the cytokines, 2 placentas for fetal-maternal transfer, and 4 additional placentas were used for an endogenous control. The ex vivo isolated cotyledon human placental perfusion model was used.

The bidirectional transfer and fetal vascular pressure changes due to the presence of 125I-labeled inhibin A in the ex-vivo human placental model.

Objective: The purpose of this study was to investigate the transport of inhibin A and to determine its effects on fetal vascular pressure at elevated levels in the human placenta using 125I-labeled synthetic glycoprotein.

Methods: Synthetic inhibin A was prepared and was shown to be consistent with the natural form by high-pressure liquid chromatography (HPLC) and molecular weight determination by gas-chromatography mass spectrometry. The standardized Na125I process yielded 125I-labeled inhibin A with a radioactivity of 10(6) cpm/microg.

Oxytocin preparation stability in several common obstetric intravenous solutions.

Objective: The purpose of this study was to determine the stability of oxytocin in lactated Ringer's solution and lactated Ringer's-dextrose 5% solution over a 24-hour period at 25 degrees C and over a 7-day period at 5 degrees C.

Study Design: Twenty units (2.1 microg equal 1 unit) of oxytocin were injected into 1000 mL of lactated Ringer's solution and lactated Ringer's-dextrose 5% solution.

The MHC class I-related receptor, FcRn, plays an essential role in the maternofetal transfer of gamma-globulin in humans.

The transfer of maternal gamma-globulin (IgG) provides the neonate with humoral immunity during early life. In humans, maternal IgG is transported across the placenta during the third trimester of pregnancy. The expression of the MHC class I-related receptor, FcRn, in the human placenta suggests that this Fc receptor might be involved in the delivery of maternal IgG, but direct evidence to support this is lacking.

Ex vivo human placental transfer of trovafloxacin.

Objective: The purpose of this study was to determine the ex vivo human placental transfer of trovafloxacin from the maternal circulation to the fetal circulation.

Methods: Six placentas from uncomplicated, term, vaginal or cesarean deliveries were studied using the ex vivo isolated cotyledon perfusion chamber; 14C-antipyrine was used as a reference compound to determine the clearance index (CI) of trovafloxacin.

Results: The CI of trovafloxacin was 0.

Ex vivo human placental transfer and the vasoactive properties of hydralazine.

Objective: The purpose of this study was to determine the placental transfer and fetal vascular effects of hydralazine in an ex vivo human placental system.

Study Design: Nine placentas from uncomplicated term vaginal or cesarean deliveries were studied by means of the ex vivo single-cotyledon perfusion system. Antipyrine was used for the reference compound in the determination of the clearance index of hydralazine.

The ex vivo human placental transfer of the anti-HIV nucleoside inhibitor abacavir and the protease inhibitor amprenavir.

Objective: The transfer of abacavir, a new nucleoside inhibitor, and amprenavir, a new protease inhibitor, used for the treatment of human immunodeficiency virus, has been studied in the ex vivo human placental model.

Methods: The ex vivo human placental model used C14 antipyrine to determine the transport fraction and clearance index of these compounds at both the peak and trough serum concentrations. The clearance index accumulation and tissue concentrations were determined for each drug by high pressure liquid chromatography.

Placental transfer of ritonavir with zidovudine in the ex vivo placental perfusion model.

Objective: The object was to determine the placental transfer of ritonavir alone and in combination with zidovudine.

Study Design: Twelve placental perfusion studies were performed at trough (1-2 microg/mL) and peak (approximately 20 microg/mL) combinations of ritonavir and zidovudine. Accumulation of ritonavir was determined.

The maternal-fetal transfer of lamivudine in the ex vivo human placenta.

Objective: Our purpose was to measure the transfer of lamivudine ([-]-2'-deoxy-3'-thiacytidine) across the human placenta both alone and in the presence of zidovudine.

Study Design: Nine placentas from term, elective cesarean deliveries were analyzed with use of the ex vivo single cotyledon perfusion system. Antipyrine was used as the reference compound to measure the clearance index values of lamivudine alone and in combination with zidovudine.

Ex vivo human placental transfer of anti-human immunodeficiency virus compounds.

Objective: The transfer of anti-human immunodeficiency virus (HIV) drugs has been studied in the ex vivo human placental model. There is a paucity of information on the placental transfer of these drugs because of ethical considerations and the expense involved in the use of the non-human primate model.

Methods: The standardized ex vivo human placental model was used in these studies and the clearance index in relationship to antipyrine was used to determine the role of transfer of non-nucleosides, nucleosides, and a protease inhibitor.

Ampicillin for neonatal group B streptococcal prophylaxis: how rapidly can bactericidal concentrations be achieved?

Objective: Our purpose was to determine how rapidly bactericidal concentrations of ampicillin against group B streptococci are achieved in amniotic fluid and cord blood after a 2 gm maternal infusion.

Study Design: Ampicillin was administered at varying time intervals between 3 and 67 minutes before elective cesarean delivery in 40 women. Samples of amniotic fluid were obtained by amniocentesis just before the uterine incision was made.

Clearance of ticarcillin-clavulanic acid by continuous venovenous hemofiltration in three critically ill children, two with and one without concomitant extracorporeal membrane oxygenation.

Three children were receiving ticarcillin-clavulanic acid by continuous venovenous hemofiltration (CVVH). Two of them were also receiving concomitant extracorporeal membrane oxygenation (ECMO). We collected ultrafiltrate hourly to determine the clearance of ticarcillin-clavulanic acid by CVVH.

Ex vivo human placental transfer of rifampin and rifabutin.

Objective: The purpose of this study was to determine the ex vivo human placental transfer of rifampin and rifabutin.

Methods: Seven placentas from uncomplicated term vaginal or cesarean deliveries were studied utilizing the ex vivo single cotyledon perfusion system. Antipyrine was used for the reference compound in the determination of the clearance indices of rifampin and rifabutin.

Markers of acute and chronic asphyxia in infants with meconium-stained amniotic fluid.

Objective: Cord blood pH, lactate, hypoxanthine, and erythropoietin levels have all been used as markers of either acute or chronic asphyxia. We sought to determine whether these index values were significantly different in infants with or without meconium-stained amniotic fluid.

Study Design: Fifty-six pregnant women in spontaneous labor at term were divided into two groups on the basis of the presence or absence of meconium-stained amniotic fluid.

Ex vivo human placental transfer of human immunodeficiency virus-1 p24 antigen.

Objective: Our purpose was to determine whether human immunodeficiency virus-1 p24 antigen crosses the human placenta and, if so, to determine its clearance index relative to antipyrine.

Study Design: Eight term human placentas from uncomplicated vaginal or cesarean section deliveries were studied by ex vivo placental perfusion to determine the incidence and concentration required to obtain passage of p24 antigen into the fetal circulation. The concentration of p24 antigen was determined by antigen-capture enzyme immunoassay.

Teratogenic and embryocidal effects of Zidovudine (AZT) in sprague-dawley rats.

Objective: The purpose of the present investigation was to analyze the effets of zidovudine on the postimplantation embryo and fetus.

Methods: Pregnant Sprague-Dawley rats were given various doses (10 mg/kg, 30 mg/kg, 150 mg/kg) of zidovudine or saline by an endotracheal tube during the period of embryogenesis (days 6-8, 9-11, 6-11 postconception). The animals were sacrificed on days 18-19 of pregnancy, and their fetuses were removed by hysterotomy.

The maternal-fetal transfer of bisheteroypiperazine (U-87201-E) in the ex vivo human placenta.

Objective: The purpose of this study was to elucidate the maternal-fetal transfer of bisheteroypiperazine (U-87201-E), a nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus-1.

Study Design: Placentas from normal term deliveries were used in this study to determine the maternal-fetal transfer of bisheteroypiperazine. The studies were conducted at several concentrations with the circulation either open-open or closed-closed.

The transfer of the nucleoside analog ganciclovir across the perfused human placenta.

Objective: The purpose of this study was to compare the maternal-fetal placental transfer of the antiviral nucleoside analog ganciclovir to that of acyclovir and to investigate the mechanism of transport.

Study Design: The ex vivo human placental cotyledon model was used. Carbon 14-labeled antipyrine was used as the reference compound to determine the clearance index of both antiviral agents.