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D M Nelson

Publications and source records attributed to D M Nelson.

At least 37 records · Page 2Linked to original sources
PubMed2000

Peroxisome proliferator-activated receptor-gamma modulates differentiation of human trophoblast in a ligand-specific manner.

The ligand-dependent nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARgamma) regulates the differentiation of several tissues and cell types. PPARgamma was recently determined to be essential for murine placental development and differentiation. We therefore assessed the influence of PPARgamma on differentiation of human placental trophoblasts. We initially used immunohistochemistry to examine term human placentas for PPARgamma expression and found that PPARgamma is present in syncytiotrophoblasts and cytotrophoblasts in placental villi. We correlated the expression of PPARgamma with differentiation of primary human trophoblasts and found that 8-bromo-cAMP, a known enhancer of trophoblast differentiation, stimulates PPARgamma activity, but has no effect on PPARgamma expression. We demonstrated that the PPARgamma ligand 15-deoxy-delta12,14-prostaglandin J2 (15deltaPGJ2) and the thiazolidinedione troglitazone stimulate PPARgamma activity in the trophoblast cell line BeWo. Importantly, whereas exposure of cultured primary trophoblasts to troglitazone enhances biochemical and morphological trophoblast differentiation, 15deltaPGJ2 diminishes trophoblast differentiation. Furthermore, 15deltaPGJ2, but not troglitazone, up-regulates p53 expression and promotes trophoblast apoptosis. These data indicate that PPARgamma is expressed in human placental trophoblasts, and that ligand-specific activation of PPARgamma results in opposing effects on trophoblast differentiation. Our results suggest that PPARgamma plays an important role in placental differentiation during human pregnancy.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

In vitro modulation of the expression of 15-hydroxy-prostaglandin dehydrogenase by trophoblast differentiation.

OBJECTIVE: Our goal was to determine the expression and activity of 15-hydroxy-prostaglandin dehydrogenase, a prostaglandin-metabolizing enzyme, in differentiating trophoblasts in vitro. STUDY DESIGN: Cytotrophoblasts from placentas of term healthy women were cultured in either Ham's-Waymouth medium, which hinders the process of cytotrophoblast differentiation, or medium 199, which facilitates differentiation into syncytiotrophoblasts. 15-Hydroxy-prostaglandin dehydrogenase expression was determined with Western immunoblotting, and activity was measured by a specific enzyme immunoassay of 13, 14-dihydro-15-keto prostaglandin F2 alpha, an inactive product of 15-hydroxy-prostaglandin dehydrogenase activity. RESULTS: The expression and activity of 15-hydroxy-prostaglandin dehydrogenase were enhanced during trophoblast differentiation and were higher in cells grown in medium 199 than in those grown in Ham's-Waymouth medium. 8-Bromo-cyclic adenosine monophosphate, which stimulates prostaglandin H synthase-2 expression, diminished the expression and activity of 15-hydroxy-prostaglandin dehydrogenase in concentration- and time-dependent manners. CONCLUSIONS: 15-Hydroxy-prostaglandin dehydrogenase expression and activity are regulated during trophoblast differentiation and by cyclic adenosine monophosphate. Coordinated expression of l5-hydroxy-prostaglandin dehydrogenase and prostaglandin H synthase-2 contributes to the regulation of prostaglandin release from trophoblasts.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1999

Hypoxia limits differentiation and up-regulates expression and activity of prostaglandin H synthase 2 in cultured trophoblast from term human placenta.

OBJECTIVE: We determined the effect of hypoxic conditions on cellular differentiation and prostaglandin H synthase expression in cultured human term trophoblast. STUDY DESIGN: Cytotrophoblasts isolated from term placentas were cultured for 24-72 hours in a standard (20% oxygen) or hypoxic (1% to 2% oxygen) atmosphere. Trophoblast biochemical differentiation was determined by release of human chorionic gonadotropin. Morphologic differentiation was evaluated by epifluorescent and confocal microscopic examination of cultures after dual cytochemical staining for surface membrane desmosomes and intracytoplasmic nuclei. Prostaglandin H synthase 2 expression was determined by Western blot analysis and correlated with enzyme activity by immunoassay of 2 prostaglandin H synthase 2 products, prostaglandin E2 and thromboxane. RESULTS: Human chorionic gonadotropin levels in media and syncytiotrophoblast formation were markedly diminished in trophoblast cultured in hypoxia, compared with trophoblast in control cultures, whereas viability was unchanged. Hypoxia up-regulated expression of trophoblast prostaglandin H synthase 2 but not of prostaglandin H synthase 1 and increased prostaglandin E2 and thromboxane release. CONCLUSIONS: Hypoxia limits differentiation and enhances prostaglandin H synthase 2 expression in cultured villous trophoblast. These responses may account for the cytotrophoblast prominence characteristic of placentas exposed to attenuated oxygen delivery.

Blotting, Western↗
PubMed1999

Gene therapy for severe combined immunodeficiency caused by adenosine deaminase deficiency: improved retroviral vectors for clinical trials.

Severe combined immunodeficiency (SCID) caused by adenosine deaminase deficiency (ADA-) is the first genetic disorder to be treated with gene therapy. Since 1990 when the first trial started for 2 patients with ADA- SCID, five clinical trials enrolling 11 patients have been conducted with different clinical approaches and the results obtained from these trials have recently been reported. According to these reports, T cell-directed gene transfer was useful in the treatment of ADA- SCID whereas the retroviral-mediated gene transfer to hematopoietic stem cells was insufficient for achievement of clinical benefits. This chapter reviews several crucial problems inherent in the current retroviral technology based on the clinical data observed in these pioneering ADA gene therapy trials and presents our new retroviral vector system for the next stem cell gene therapy.

Adenosine Deaminase↗
PubMed1998

Ex vivo fibroblast transduction in rabbits results in long-term (>600 days) factor IX expression in a small percentage of animals.

Delivery of human factor IX to the circulation was analyzed in rabbits by ex vivo fibroblast transduction followed by subcutaneous implantation. Kinetic studies of human factor IX in rabbits demonstrated a half-life of approximately 16 hr and a volume distribution of 22%, where intraperitoneal and subcutaneous bioavailability was three- to sevenfold lower than by intravenous administration. Ex vivo retroviral transduction of autologous fibroblasts was performed on 15 animals. After subcutaneous injection of fibroblast-collagen mixtures, the expression of human factor IX in rabbit plasma was followed by ELISA. Of 15 rabbits injected, expression of human factor IX was detected in 2 animals, and expression was long term (>600 days). One animal had stable levels of human factor IX, at 20 ng/ml, while the second animal had lower and gradually decreasing levels of human factor IX. There were no gross differences in pathology at the injection sites, when comparing animals with human factor IX in plasma and those without. Immunological studies demonstrated antibody formation in response to injection mixture components (including human factor IX), but again there was no correlation with immune response and long-term factor IX production in animals. Tissues at the implantation sites were positive for factor IX DNA by PCR analysis, regardless of whether there was detectable plasma factor IX or not. Small numbers of PCR-positive cells were detected in the internal organs of the long term-expressing rabbits while similar tissues were negative in nonexpressing animals.

Animals↗
PubMed1998

Characterization of diverse viral vector preparations, using a simple and rapid whole-virion dot-blot method.

A number of different viruses have been adapted as gene transfer vectors, including retroviruses, adenoviruses, adenoassociated viruses (AAVs), herpes simplex virus, SV40 viruses, and alphaviruses (both Semliki Forest and Sindbis viruses). One of the major rate-limiting and time-consuming steps in the characterization of these vectors is the process of determining the viral vector titers. In addition, there is no "universal" method that can be used to rapidly estimate the titer and the utility of viral vector preparations. We demonstrate here that supernatant from diverse classes of viral vectors, with either RNA or DNA genomes, can be rapidly evaluated by a simple virus dot-blot hybridization without prior extraction of nucleic acids. This system can provide a reliable screen for physical titer of viral vector supernatants in 1 day.

Adenoviridae↗
PubMed1998

Opposing actions of prostaglandins and oxytocin determine the onset of murine labor.

Prostaglandins (PGs) have been recently proven essential for parturition in mice. To dissect the contributions of the two cyclooxygenase (COX) isoforms to the synthesis of PGs during pregnancy, we have characterized the parturition phenotype of COX-1-deficient mice. We find that mice with targeted disruption of the COX-1 gene have delayed parturition resulting in neonatal death. Results of matings of COX-1-deficient females with COX-1 intact males, and blastocyst transfer of COX-1-deficient or -intact embryos into wild-type foster mothers, proved necessity and sufficiency of maternal COX-1 for the normal onset of labor. COX-1 expression is induced in gravid murine uterus and by in situ hybridization; this induction is localized to the decidua. Measurement of uterine PGs further confirmed that COX-1 accounted for the majority of PGF2alpha production. To evaluate the interaction of PGs with oxytocin during murine labor, we generated mice deficient in both oxytocin and COX-1. Surprisingly, the combined oxytocin and COX-1-deficient mice initiated labor at the normal time. COX-1-deficient mice demonstrated impaired luteolysis, as evidenced by elevated serum progesterone concentration and ovarian histology late in gestation, and delayed induction of uterine oxytocin receptors. In contrast, simultaneous oxytocin and COX-1 deficiency restored the normal onset of labor by allowing luteolysis in the absence of elevated PGF2alpha production. These findings demonstrate that COX-1 is essential for normal labor in the mouse, with a critical function being to overcome the luteotrophic action of oxytocin in late gestation.

Animals↗
PubMed1998

Lipopolysaccharide enhances the transcription of prostaglandin H synthase-2 gene in primary human trophoblasts.

OBJECTIVE: Our purpose was to test the hypothesis that lipopolysaccharide potentiates the transcription of human placental prostaglandin H synthase-2 gene, a rate-limiting enzyme in prostaglandin synthesis. STUDY DESIGN: We transfected normal term cytotrophoblasts with a reporter vector containing either prostaglandin H synthase-1 or prostaglandin H synthase-2 promoters, cloned upstream of a luciferase. We correlated lipopolysaccharide effect on luciferase activity with enzyme expression and prostaglandin E2 production. RESULTS: Lipopolysaccharide (10 microg/ml) enhanced prostaglandin H synthase-2 but not prostaglandin H synthase-1 promoter activity. This effect was abolished by dexamethasone (10(-6) mol/L). Platelet-derived growth factor, a known stimulant of prostaglandin H synthase-2 in nonplacental tissue, had no effect on the activity of prostaglandin H synthase-2 promoter. Lipopolysaccharide induced the expression of prostaglandin H synthase-2 messenger ribonucleic acid fivefold to sixfold and caused a 3.5-fold increase in prostaglandin E2 production. CONCLUSION: Lipopolysaccharide enhances the transcription of prostaglandin H synthase-2 gene in human trophoblasts. Enhanced expression of prostaglandin H synthase-2 results in a higher production of prostaglandins, which may alter villous blood flow.

Anti-Inflammatory Agents↗
PubMed1998

The release of 15-hydroxyeicosatetraenoic acid by human placental trophoblast is increased in preeclampsia.

OBJECTIVE: We tested the hypothesis that trophoblast produces 15-hydroxyeicosatetraenoic acid, and its level is elevated in trophoblast from preeclamptic women compared with normal. We also used selective enzymatic inhibitors to determine the relative contributions of 15-lipoxygenase and the two isozymes of prostaglandin H synthase to 15-hydroxyeicosatetraenoic acid levels. STUDY DESIGN: Cytotrophoblasts isolated from placentas of normal or preeclamptic women were cultured in the presence or absence of enzyme inhibitors. Media levels of 15-hydroxyeicosatetraenoic acid were measured by radioimmunoassay. RESULTS: When compared with normal pregnancies, cytotrophoblasts from preeclamptic pregnancies released up to fivefold higher levels of 15-hydroxyeicosatetraenoic acid. Aspirin, an inhibitor of both the prostaglandin H synthase-1 and prostaglandin H synthase-2 isozymes, and nordihydroguaiaretic acid, a selective inhibitor of lipoxygenases, both significantly inhibited 15-hydroxyeicosatetraenoic acid production. In contrast, the selective prostaglandin H synthase-2 inhibitor NS-398 had no effect on 15-hydroxyeicosatetraenoic acid release in the absence of aspirin, but NS-398 reduced 15-hydroxyeicosatetraenoic acid levels in normal trophoblast pretreated with aspirin. CONCLUSIONS: The data indicate that 15-hydroxyeicosatetraenoic acid is produced in trophoblasts and its release by cytotrophoblasts is higher in preeclamptic pregnancies compared with normal controls. Both lipoxygenase and prostaglandin H synthase contribute to 15-hydroxyeicosatetraenoic acid production, and aspirin reduces 15-hydroxyeicosatetraenoic acid secretion. We suggest 15-hydroxyeicosatetraenoic acid plays a role in the oxidation of lipoproteins and the endothelial damage characteristic of preeclampsia.

Aspirin↗
PubMed1998

Gene expression of nitric oxide synthase in cultured human term placental trophoblast during in vitro differentiation.

The human placental syncytiotrophoblast is derived from differentiating cytotrophoblasts and is in contact with maternal blood. This endothelial function positions the trophoblast to regulate maternal-fetal exchange and to influence circulatory dynamics through paracrine interactions in the placenta. Two isoforms of nitric oxide synthase (NOS) are expressed in placenta, and northern analysis, reverse transcription-polymerase chain reaction (RT-PCR), and immunocytochemistry were used to correlate expression of the type II, inducible NOS (iNOS) and the type III, endothelial NOS (eNOS) with state of differentiation in cultured trophoblast from term placentae. It was also tested whether cytokines known to induce NOS in other cell systems would induce iNOS in human trophoblast. The mRNA for eNOS was detected by RT-PCR, but not by Northern analysis, in cultures grown for 24 h when cytotrophoblasts were dominant. In contrast, eNOS mRNA was abundant in cultures grown for 72 h when syncytiotrophoblast was present. Immunocytochemical staining for eNOS protein showed specific fluorescence in a few cells in cultures at 24 h, but the vast majority of cells expressed eNOS at 72 h. The iNOS isoform was expressed neither basally in any trophoblast culture nor was this isoform induced in cultures exposed to interleukin-1, tumour necrosis factor-alpha, interferon-gamma and lipopolysaccharide. The in vitro pattern of trophoblast eNOS expression models the in vivo pattern of eNOS expression described for villous trophoblast. The results suggest that eNOS plays a role in human trophoblast differentiation and function.

Base Sequence↗
PubMed1998

Development of improved adenosine deaminase retroviral vectors.

A series of adenosine deaminase (ADA) retroviral vectors were designed and constructed with the goal of improved performance over the PA317/LASN vector currently used in clinical trials. First, the bacterial selectable-marker neomycin phosphotransferase (neo) gene was removed to create a "simplified" vector. Second, the Moloney murine leukemia virus long terminal repeat (LTR) promoter used for ADA expression was replaced with either the myeloproliferative sarcoma virus (MPSV) or SL3-3 LTR. Supernatant from each ADA vector was used to transduce ADA-deficient (ADA-) B- and T-cell lines as well as primary peripheral blood mononuclear cells (PBMC) from an ADA- severe combined immunodeficiency patient. Total ADA enzyme activity and ADA activity per integrant in the transduced cells demonstrated that the MPSV LTR splicing vector design provided the highest level of ADA expression per cell. This ADA(MPSV) vector was then tested in packaging cell lines containing either the gibbon ape leukemia virus envelope (PG13 cells), the murine amphotropic envelope (FLYA13 cells), or the feline endogenous virus RD114 envelope (FLYRD18 cells). The results indicate that FLYRD18/ADA(MPSV), a simplified ADA retroviral vector with the MPSV LTR, provides a 17-fold-higher level of ADA expression in human lymphohematopoietic cells than the PA317/LASN vector currently in use.

Adenosine Deaminase↗
PubMed1998

Troglitazone use in insulin-treated type 2 diabetic patients. The Troglitazone Insulin Study Group.

OBJECTIVE: To determine the ability of troglitazone to reduce requirements for injected insulin while maintaining blood glucose levels in insulin-treated patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This 26-week double-blind study with open-label extension included patients who had failed previous oral antidiabetic medication and took > or =30 but <150 U of insulin daily The 222 patients in the double-blind study received 200 or 400 mg troglitazone once daily or matching placebo. The primary end point was the proportion of patients meeting the target of > or =50% reduction in injected insulin and either a 15% reduction in fasting blood glucose or a blood glucose <7.8 mmol/l. Insulin dose was reduced 25% based on a study-specific algorithm whenever fasting blood glucose was reduced 5% from baseline. Also of interest were changes in insulin dose and HbA1c. The open-label extension included 173 patients. They received 200 mg of troglitazone with optional titration to 400 mg, and insulin dose was adjusted based on investigators' standards of care. Open-label measures were change in insulin dose, HbA1c, and fasting serum glucose (FSG). RESULTS: In the double-blind phase, 22 and 27% of the 200- and 400-mg troglitazone groups, respectively, reached target, compared with placebo (7%) (P < 0.01). Insulin dose reductions of 13 +/- 3, 30 +/- 3, and 41 +/- 3 U were observed for placebo, 200-, and 400-mg troglitazone groups, respectively HbA1c decreased 0.09 +/- 0.14% for placebo, 0.13 +/- 0.14% for 200 mg, and 0.41 +/- 0.14% for 400 mg (P < 0.05) troglitazone. In the open-label extension, troglitazone treatment resulted in >50% reduction from baseline in daily insulin dose and decreases in HbA1c of 1% and in FSG of >17%. CONCLUSIONS: Troglitazone decreases daily injected insulin dose requirements and improves glycemic control in insulin-treated patients with type 2 diabetes.

Adult↗
PubMed1997

A simple and reliable method for screening retroviral producer clones without selectable markers.

Simplified retroviral vectors that lack dominant selectable markers are being used with increasing frequency. These simplified vectors may offer a number of advantages over selectable marker-containing constructs, including potentially higher titers and less immunogenicity. However, the use of these vectors has been limited by the cumbersome experimental approaches in establishing and characterizing useful producer cell clones. To address this issue, a simple and reliable assay was developed to identify retroviral producer cell lines with or without dominant selectable markers. Producer cells were first generated by standard transfection/transduction and clones isolated by limiting dilution. Supernatant from each clone was then screened by RNA dot blot to identify the best producer clone candidates. The semiquantitative nature of the RNA dot blot assay was validated using a retroviral vector containing neomycin phosphotransferase (neo). Titers obtained by conventional G418-resistant colony forming units/ml (G418(R) cfu/ml) assays strongly correlated with the values by RNA dot blot procedure. RNA dot blot results also correlated well with titers estimated by Southern analysis of HeLa cells transduced with supernatant from each clone. The RNA dot blot technique is a rapid (2 days) and reliable method to screen retroviral producer cells, thereby facilitating the generation and characterization of simplified retroviral producer cell clones.

Animals↗
PubMed1997

In vivo retrovirus-mediated gene transfer into multiple hematopoietic lineages in rabbits without preconditioning.

Hematopoietic progenitor cells are attractive targets for gene therapy of inherited and acquired disorders. We have developed a novel procedure for mediating gene transfer into hematopoietic cells using an in vivo approach. The procedure involves injection of irradiated retroviral producer cells into the femoral bone marrow cavity in rabbits without preconditioning. The emergence of vector-marked cells in multiple peripheral blood hematopoietic lineages was detected 1 week post-injection and persisted until the animals were sacrificed up to 20 months later. Vector-marked cells were also detected in different hematopoietic tissues including bone marrow, spleen, thymus, and lymph node. Expression of retrovirus-specific messages by reverse transcription polymerase chain reaction was detected at multiple time points up to 20 months. Retrovirally encoded protein was detected by enzyme-linked immunosorbent assay in supernatant from cultures of granulocytes isolated 14 months after the procedure. This work demonstrates the feasibility of effecting gene transfer into hematopoietic progenitor cells in vivo.

Animals↗
PubMed1997

Ontogenetic and phylogenetic evaluation of the presence of fibrin-type fibrinoid in the villous haemochorial placenta.

The hypothesis that fibrin type fibrinoid deposition on villi is unique to the term human placenta was tested. Bright-field microscopy was used to examine sections of first and second trimester human placental villi and tissues from three animal species that have villous haemochorial placentae similar to the human: the armadillo, the baboon and the rhesus. Sections stained with haematoxylin and eosin showed fibrin type fibrinoid deposits were hypocellular, eosinophilic masses attached to the surface of villi examined from both the human and the animal species. The deposits were located at discontinuities in the syncytiotrophoblast layer, and the fibrinoid provided a matrix for trophoblast re-epithelization of the villous surface. It is concluded that fibrin-type fibrinoid is not unique to the term human placenta. The presence of the syncytiotrophoblast discontinuities associated with the fibrinoid deposition must be considered in models of maternal-fetal exchange in the villous haemochorial placenta.

Animals↗
PubMed1997

Aspirin induces increased expression of both prostaglandin H synthase-1 and prostaglandin H synthase-2 in cultured human placental trophoblast.

OBJECTIVE: We tested the hypothesis that aspirin affects trophoblast like other epithelial cells do, by inhibiting prostanoid production, inducing prostaglandin H synthase-2 expression, and enhancing secretion of 15-hydroxyeicosatetraenoic acid. STUDY DESIGN: Cytotrophoblast from placentas (n = 15) of uncomplicated singleton pregnancies were cultured in medium 199 for 4 to 72 hours in the presence or absence of aspirin. RESULTS: Aspirin (10(-4) M) inhibited (p < 0.01) average trophoblast prostaglandin E2 release by 60% and thromboxane B2 by 86%. Western immunoblotting showed the prostaglandin H synthase-1 was constitutively expressed in cytotrophoblast, and aspirin treatment caused a twofold increase in prostaglandin H synthase-1 expression. Prostaglandin H synthase-2 was also constitutively expressed in untreated cytotrophoblast but at lower levels than prostaglandin H synthase-1. Aspirin enhanced prostaglandin H synthase-2 expression in trophoblast cultures, but prostaglandin H synthase-2 contributed a range of only 10% to 33% (n = 4) of the total cellular prostaglandin H synthase protein pool even after aspirin induction. The increased prostaglandin H synthase expression depended on both transcription and translation because actinomycin D and cycloheximide each inhibited the increased prostaglandin H synthase protein expression after aspirin treatment. The aspirin induction of prostaglandin H synthase was accompanied by decreased release of 15-hydroxyeicosatetraenoic acid. CONCLUSIONS: Trophoblast differs from other cells studied because aspirin enhances expression of both prostaglandin H synthase-1 and prostaglandin H synthase-2 isozymes while decreasing, instead of increasing, the secretion of 15-hydroxyeicosatetraenoic acid. The aspirin effects on prostaglandin H synthase synthesis and 15-hydroxyeicosatetraenoic acid release in trophoblast suggest that the mechanisms of action for aspirin in the prophylaxis of preeclampsia may be more diverse than simply altering platelet thromboxane production.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1997

Drug actions in preeclampsia: aspirin, but not magnesium chloride or dihydralazine, differentially inhibits cultured human trophoblast release of thromboxane and prostacyclin without affecting angiotensin II, endothelin-1, or leukotriene B4 secretion.

OBJECTIVE: We hypothesized that aspirin Mg++, and dihydralazine affect the release of vasoactive agents from cultured human placental trophoblast. STUDY DESIGN: Cytotrophoblasts isolated from placentas of preterm or term deliveries of 14 healthy control women and 15 preeclamptic women were cultured in Dulbecco's modified Eagle's medium for 5 days in the presence or absence of either 0.1 mmol/L aspirin, 3 mmol/L magnesium chloride, or 136 ng/ ml dihydralazine. Vasoactive substances were quantitated by radioimmunoassay with mean +/- SEM percentage of untreated cells (= 100%) compared by the Mann-Whitney U test and analysis of variance. RESULTS: Aspirin inhibited (p < 0.01) both thromboxane and prostacyclin on days 1 and 2 in culture but not on days 3 to 5 unless the Dulbecco's modified Eagle's medium was supplemented with arachidonic acid. Aspirin inhibition was greater (p < 0.01) for thromboxane in cells cultured 24 hours after preeclamptic pregnancy (preterm 29.9% +/- 6.8%, term 20.1% +/- 5.9%) compared with normal controls (preterm 66.3% +/- 10.6%, term 68.9% +/- 11.6%). Aspirin reduced (p < 0.01) the ratio of thromboxane to prostacyclin in media of cells from preeclampsia (untreated 27.8 +/- 7.2, aspirin 13.3 +/- 4.4), but aspirin had no effect on this ratio in cultures from control normal pregnancies (untreated 6.8 +/- 2.9, aspirin 4.8 +/- 1.1). Neither magnesium chloride nor dihydralazine affected trophoblast prostanoid production, and no drug altered the media levels of angiotensin II, endothelin-1, or leukotriene B4. CONCLUSION: Aspirin selectively inhibits trophoblast prostanoid production. This inhibition depends on the availability of arachidonic acid and the presence or absence of preeclampsia. Magnesium and dihydralazine effects in pregnancy are not related to altered release of trophoblast vasoactive compounds.

Angiotensin II↗