ABSTRACT
Premature delivery occurs in 12% of all births, accounts for nearly half of neonatal morbidity and is increasing in frequency. Current therapeutic approaches to preterm delivery are ineffective and present serious risks to both the mother and fetus. Although there are multiple factors that contribute to the etiology of preterm birth, the single most common cause is infection. Recently, using cDNA microarray analysis of human placental tissue, we demonstrated that human placental matrix metalloproteinase-1 (MMP-1) is upregulated during labor. In a separate line of investigation, we have shown that blockade of endothelin-1 (ET-1) action through the use of an endothelin-converting enzyme-1 (ECE-1) inhibitor, an established commercially available endothelin receptor antagonist or a novel quinolone-derived endothelin receptor antagonist synthesized by our group also prevents preterm labor and delivery in a mouse model. We have now shown that induction of preterm labor with lipopolysaccharide in our mouse model is associated with increased levels of MMP-1. Furthermore, we showed that silencing the ECE-1/ET-1 pathway by using ECE-1 RNA interference prevents both the onset of preterm labor and upregulation of MMP-1. The data indicate that ET-1 and MMP-1 act in the same molecular pathway in preterm labor.
Subject(s)
Aspartic Acid Endopeptidases/metabolism , Inflammation/prevention & control , Metalloendopeptidases/metabolism , Premature Birth/prevention & control , RNA Interference , Animals , Aspartic Acid Endopeptidases/antagonists & inhibitors , Endothelin-1/antagonists & inhibitors , Endothelin-1/metabolism , Endothelin-Converting Enzymes , Female , Gene Knockdown Techniques , Matrix Metalloproteinase 13/metabolism , Metalloendopeptidases/antagonists & inhibitors , Mice , Mice, Inbred C57BL , Models, Animal , Obstetric Labor, Premature , Placenta/metabolism , Pregnancy , Tocolysis , Uterus/metabolismABSTRACT
BACKGROUND: Late postpartum eclampsia is more frequently recognized than past reports indicate. This report describes the association of a reversible encephalopathy in a woman with late postpartum eclampsia. CASE: A woman with lupus nephritis presented 7 days postpartum with eclampsia. Postseizure findings included dramatic short-term memory loss. Although a computed tomography scan was negative, subsequent magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) demonstrated vascular changes associated with a reversible encephalopathy. Conservative treatment with analeptic and antihypertensive therapy allowed a rapid resolution of all symptomatology. CONCLUSION: In women with eclampsia and unusual neurologic findings, an MRI/MRA may be useful even in the presence of a negative computed tomography scan.
Subject(s)
Eclampsia/diagnosis , Memory Disorders/etiology , Posterior Leukoencephalopathy Syndrome/complications , Posterior Leukoencephalopathy Syndrome/diagnosis , Puerperal Disorders/diagnosis , Adult , Female , Humans , Lupus Nephritis/complications , Magnetic Resonance Angiography , Magnetic Resonance Imaging , Memory Disorders/diagnosis , Memory, Short-Term , PregnancyABSTRACT
Background. We report a case of familial hyperlipidemia in pregnancy that resulted in hemorrhagic pancreatitis. Case. A patient at 27-week gestation was admitted for recurrent pancreatitis secondary to severe hyperlipidemia. With conservative care, the patient improved but on the fourth day of admission she experienced a sudden onset of hypotension and was diagnosed with hemorrhagic pancreatitis. Conclusion. Pancreatitis caused by hyperlipidemia is an uncommon event during pregnancy. A familiarity with the severe complications associated with this potentially life-threatening condition is important.
ABSTRACT
OBJECTIVE: Several matrix metalloproteinases (MMP) have been implicated in preterm parturition. We hypothesized that administration of a MMP inhibitor would reduce the rate of inflammation-mediated preterm delivery and prolong gestation in a mouse model. STUDY DESIGN: We utilized an animal model of endotoxin-induced preterm delivery using timed pregnant C57Bl6 mice. Test animals received lipopolysaccharide (LPS) followed by the MMP inhibitor at 1 dose 12 hours after the LPS. Control mice received the same dose of LPS, followed by a control solution 12 hours after the LPS. The primary outcome was preterm delivery rate. RESULTS: Mice in the study group had a significantly lower rate of preterm delivery (44%) compared to 100% in the controls (P = .009). Furthermore, the latency between the administration of injection and delivery was also longer in the study group (means 28.3 hours, standard deviation 9.4 hours) than among controls (mean 15.7 hours, standard deviation 1.8 hours) (P < .001). CONCLUSION: Administration of an MMP inhibitor results in a decreased rate of inflammation-mediated preterm delivery in this animal model.
Subject(s)
Dipeptides/pharmacology , Matrix Metalloproteinase Inhibitors , Obstetric Labor, Premature/prevention & control , Protease Inhibitors/pharmacology , Animals , Female , Injections, Intraperitoneal , Mice , Mice, Inbred C57BL , Models, Animal , Pregnancy , Pregnancy Outcome , Time FactorsSubject(s)
Diseases in Twins/diagnostic imaging , Fetal Diseases/diagnostic imaging , Lung/embryology , Urethra/abnormalities , Urinary Bladder Neck Obstruction/diagnostic imaging , Adult , Amniotic Fluid/physiology , Diseases in Twins/embryology , Female , Humans , Kidney/diagnostic imaging , Kidney/embryology , UltrasonographyABSTRACT
Our objective was to describe the change in the level of troponin I in patients who undergo a vaginal or cesarean delivery. We obtained troponin I levels on admission and 1 hour after delivery in women undergoing vaginal and cesarean deliveries. Exclusion criteria included <37 weeks' gestation, a history of cardiac disease, hypertension, or cardiac symptoms. The troponin I level used to indicate myocardial ischemia was 2.0 ng/mL; levels were analyzed using the Wilcoxon test. The median age of women in the vaginal versus the cesarean group were 25.6 years and 34.4 years, and the median gestational age for both groups was 39.6 weeks. The median troponin I level before and after vaginal delivery was <0.3 ng/mL and before and after cesarean was <0.3 ng/mL. The highest level of troponin I in either group was 0.3 ng/mL. Troponin I is not elevated as a result of undergoing a vaginal or cesarean delivery. We conclude that troponin I may be used as a reliable marker to diagnose myocardial ischemia in postpartum women.
Subject(s)
Delivery, Obstetric , Troponin I/blood , Adult , Biomarkers/blood , Cesarean Section , Female , Humans , Myocardial Ischemia/diagnosis , Predictive Value of Tests , Pregnancy , Pregnancy Complications, Cardiovascular/diagnosis , Pregnancy Trimester, Third , Prenatal Diagnosis , Puerperal Disorders/diagnosisABSTRACT
OBJECTIVE: Several metallopeptidases have been implicated in both term and preterm parturition. We hypothesize that endotoxin-induced preterm delivery can be prevented by the administration of a metallopeptidase inhibitor. STUDY DESIGN: We used an animal model of endotoxin-induced preterm delivery in timed pregnancy C57Bl/6 mice. Test animals received lipopolysaccharide followed by phosphoramidon, either every 1.5 or every 3 hours. Control mice received lipopolysaccharide followed by buffer injections at the same intervals. The primary outcome was a preterm delivery rate. RESULTS: The rate of preterm delivery for the control animals was 88.0% compared with the treatment groups of 45.5% for the mice that received phosphoramidon every 3 hours and 30.8% for the group that received it every 1.5 hours (P<.01). CONCLUSION: The administration of a metallopeptidase inhibitor resulted in a decreased rate of preterm delivery in this animal model.
