- Pregnancy and preeclampsia studies
- Pregnancy-related medical research
- Birth, Development, and Health
- Assisted Reproductive Technology and Twin Pregnancy
- Nitric Oxide and Endothelin Effects
- Reproductive System and Pregnancy
- Pelvic and Acetabular Injuries
- Ectopic Pregnancy Diagnosis and Management
- Cardiovascular Issues in Pregnancy
- Gestational Diabetes Research and Management
- Neuroendocrine regulation and behavior
- Erythropoietin and Anemia Treatment
- Hemoglobinopathies and Related Disorders
- Cancer, Hypoxia, and Metabolism
- Acute Ischemic Stroke Management
- Occupational Health and Performance
- Maternal and fetal healthcare
- Electrolyte and hormonal disorders
- Eicosanoids and Hypertension Pharmacology
- Immunodeficiency and Autoimmune Disorders
- Ovarian function and disorders
- Erythrocyte Function and Pathophysiology
- Pregnancy and Medication Impact
- Prenatal Screening and Diagnostics
- High Altitude and Hypoxia
Florida College
2012-2024
University of Florida
2014-2024
Norwegian Womens Public Health Association
2022
University of Pittsburgh
2001-2020
Magee-Womens Research Institute
2000-2020
University of Toronto
2015
Texas Medical Association
2013-2014
National University of Río Cuarto
2014
Magee-Womens Hospital
2014
University Medical Center Utrecht
2014
Circulating inflammatory cytokines have been implicated in the pathogenesis of preeclampsia. To test this hypothesis, we measured plasma levels immunoreactive tumor necrosis factor (TNF)-alpha and -beta, interleukin (IL)-1 alpha IL-6 -10 women with preeclampsia, transient gestational hypertension, throughout normal pregnancy.Enzyme-linked immunosorbent assays were used subjected to extensive validation studies.The median concentration TNF-alpha was increased by twofold preeclampsia compared...
We reported previously that plasma levels, urinary excretion, and metabolic production of cyclic guanosine 3′,5′-monophosphate (cGMP) are increased in gravid rats, postulated endogenous nitric oxide (NO), a potent vasodilator immune modulator, may mediate this change. Four lines evidence now presented demonstrating biosynthesis NO during pregnancy rats: 1) Urinary excretion levels the stable metabolite, nitrate, elevated pregnant rats; nitrate is pseudopregnant rats. 2) The cGMP also...
In vitro fertilization involving frozen embryo transfer and donor oocytes increases preeclampsia risk. These in protocols typically yield pregnancies without a corpus luteum (CL), which secretes vasoactive hormones. We investigated whether CL disrupt maternal circulatory adaptations increase Women with 0 (n=26), 1 (n=23), or >1 (n=22) were serially evaluated before, during, after pregnancy. Because increasing arterial compliance is major physiological adaptation pregnancy, we assessed...
It is postulated that inadequate remodeling of the uterine spiral arteries in preeclampsia leads to focal ischemia and generation inflammatory cytokines, such as tumor necrosis factor (TNFα) interleukins (ILs), by placenta. Our objective was compare TNFα, IL-1α, IL-1β, IL-6 levels placentas from patients with normal term pregnancies. Because placenta a large heterogeneous organ, we analyzed multiple sites per On average, there 3-fold variation cytokine protein across eight for each However,...
The kidneys and other nonreproductive organs vasodilate during early gestation; however, the "pregnancy hormones" responsible for profound vasodilation of renal circulation pregnancy are unknown. We hypothesized that ovarian hormone relaxin (RLX) contributes. Therefore, we tested whether administration RLX elicits hyperfiltration in conscious adult, intact female rats. After several days treatment with either purified porcine or recombinant human 2 (rhRLX), effective plasma flow (ERPF)...
It has been hypothesized that inadequate placentation in the hypertensive disorder of pregnancy known as preeclampsia creates foci placental ischemia/hypoxia leading to elaboration factors compromise systemic endothelial function produce disease sequelae.As tumor necrosis factor-␣ (TNF␣) and interleukin-1 (IL-1) are inflammatory cytokines capable eliciting cell dysfunction, we investigated whether production these by cultured villous explants from human placenta was affected incubation...
Marked vasodilation in the kidney and other nonreproductive organs is one of earliest maternal adaptations to occur during pregnancy. Despite recognition this extraordinary physiology for over four decades, gestational hormone responsible has remained elusive. Here we demonstrate a key role relaxin, member IGF family that secreted by corpus luteum humans rodents. Using gravid rodent model, employ two approaches eliminate relaxin or its biological activity from circulation: ovariectomy...
Identifying modifiable factors that contribute to preeclampsia risk associated with assisted reproduction can improve maternal health. Vascular dysfunction predates clinical presentation of preeclampsia. Therefore, we examined if a nonphysiological hormonal milieu, state, affects vascular health in early pregnancy. Blood pressure, endothelial function, circulating progenitor cell numbers, lipid levels, and corpus luteum (CL) hormones were compared prospective cohort women infertility history...
Investigations in the rat model of pregnancy indicate an important role for corpus luteal (CL) hormone relaxin maternal circulatory and osmoregulatory changes pregnancy, which are epitomized by profound vasodilation modest hypoosmolality, respectively. In a pilot study infertile women who became pregnant through donor eggs, vitro fertilization, embryo transfer, gestational rise glomerular filtration fall plasma osmolality were markedly subdued. Because these infertile, they lacked CL...
Impaired uterine invasion by extravillous trophoblast in early gestation is implicated the genesis of preeclampsia, a potentially lethal malady human pregnancy. However, reasons for dysfunction remain unclear because virtual inaccessibility placental and tissues from women who develop absence animal models which disease spontaneously occurs. Consequently, possibility that deficient or defective maturation endometrium (decidualization) may compromise preeclampsia remains unexplored. Using...
Placental hypoxia likely plays an important role in both normal placental development and pathology. Yet, the molecular mechanisms of signaling this organ are virtually unexplored. Therefore, we investigated expression inducible transcription factors (HIF) human placentas spanning first trimester to term. Several key observations emerged: 1) HIF-1α -2α mRNA were present all gestational ages but with greater variability during early pregnancy; 2) overall, was expressed at a constant level...
Because the kidneys are vasodilated and endogenous production of nitric oxide is increased in gravid rats, we tested whether mediates renal vasodilatory response to pregnancy.Chronically instrumented, conscious rats gestational days 12-14 were studied concurrently with age-matched virgin control animals.GFR effective plasma flow (ERPF) determined by clearances inulin para-aminohippurate before during acute infusion NW-nitro-L-arginine methyl ester (NAME; 2, 20, 50 jag/min) or...
Transcription factors orchestrate the development of extraembryonic tissues. Because placental hypoxia likely plays an important role in both normal and abnormal placentation, we have been investigating hypoxia-inducible transcription (HIFs) human placenta. In this report, focus on placentas from women with preeclampsia. placenta is a large, heterogeneous organ, employed systematic unbiased approach to sampling, our results are based analyses eight biopsy sites per We observed no significant...
During pregnancy, relaxin stimulates nitric oxide (NO)-dependent renal vasodilation, hyperfiltration and reduced myogenic reactivity of small arteries via the endothelial ETB receptor subtype. Our objective in this study was to elucidate mechanisms by which receptor/NO vasodilatory pathway. Using chronically instrumented conscious rats, we demonstrated that a specific peptide inhibitor gelatinases MMP-2 -9, cyclic CTTHWGFTLC (cyclic CTT), but not control peptide, STTHWGFTLS (STT), completely...
The endogenous biosynthesis of nitric oxide (NO) is increased during gestation. To begin our investigation a possible tissue source (or sources), we examined the placenta. We postulated that analogous to endothelium blood vessels, syncytiotrophoblast (STr) cell layer lines intervillous space human placenta would express NO synthase. Our results show placental villi calcium- and calmodulin-sensitive form synthase, located mainly in microsomal fraction. By situ hybridization using riboprobe...
Renal hemodynamics increase dramatically during pregnancy, and pressor responsiveness to exogenous administration of vasoconstrictors is attenuated. We investigated whether or not vasodilatory prostaglandins mediate these phenomena. Trained, chronically instrumented, conscious pregnant rats were used. Control values glomerular filtration rate (GFR) effective renal plasma flow (ERPF) elevated at midgestation (P less than 0.01 P = 0.05 from prepregnant means, respectively), vascular resistance...