Changes in activity of cytosolic phospholipase A2 in human amnion at parturition.

OBJECTIVE: The purpose of this study was to determine whether increased cytosolic phospholipase A2 activity mediated arachidonic acid mobilization for prostaglandin synthesis in amnion at parturition. STUDY DESIGN: Amnion was collected immediately after delivery from four groups of patients: preterm (<37 weeks) with no labor or labor and term (>37 weeks) with no labor or labor and stored at -70 degrees C. Tissues were homogenized and centrifuged for 1 hour at 100,000 g, and cytosol was assayed for cytosolic phospholipase A2 activity with use of carbon 14-labeled 1-stearoyl-2 arachidonyl phosphatidylcholine plus 10 micromol/L unlabeled substrate and 5 mmol/L calcium in 10 mmol/L N-2-hydroxyethylpiperazine-N-2-ethanesulfonic acid, pH 7.4. Incubations were performed in duplicate +/- 10 micromol/L arachidonyl trifluoromethyl ketone, a specific inhibitor of cytosolic phospholipase A2 activity, at 30 degrees C for 45 minutes. RESULTS: Total cytosolic phospholipase A2 activity (in picomoles of arachidonic acid per minute per milligram of protein) calculated as the difference between the activity in the presence and absence of arachidonyl trifluoromethyl ketone was (mean +/- SE) as follows: preterm no labor (n = 7) 8.94 +/- 3.08, preterm with labor (n = 6) 6.79 +/- 2.31, term no labor (n = 7) 14.85 +/- 1.66, and term with labor (n = 5) 5.51 +/- 1.52. Enzyme activity increased with gestational age and was highest in the term no labor group. A significant decrease in cytosolic phospholipase A2 activity occurred with labor (p < 0.05). The greatest decrease in activity was in the term group (p < 0.05). CONCLUSION: Total cellular cytosolic phospholipase A2 activity in amnion is highest in anticipation of labor but during labor total activity is depleted, resulting in the low activity measured after delivery of the placenta. The substrate specificity and changes in amnion total cytosolic phospholipase A2 activity with labor strongly suggests a role in mediation of arachidonic acid mobilization and prostaglandin synthesis at labor.

Immunohistochemical localization of phospholipase A2 isoforms in human myometrium during pregnancy and parturition.

OBJECTIVE: The purpose of this study was to localize secretory phospholipase A2 and cytosolic phospholipase A2 isoforms in pregnant human myometrium and to determine changes in expression with gestational age or parturition. STUDY DESIGN: Myometrium was collected at cesarean section at term (>37 weeks) or preterm (<37 weeks) from patients who were or were not in labor (n = 5 each group). Frozen sections were incubated with specific monoclonal antibodies against secretory phospholipase A2 or cytosolic phospholipase A2 and immunostaining visualized with the Vectastain ABC method. The intensity of immunostaining in different cellular localizations was scored by an investigator blinded to tissue identity and compared among tissues with use of the Mantel-Haenszel chi2 test. RESULTS: Secretory phospholipase A2 immunostaining was dispersed in the perinuclear region throughout the myometrial smooth muscle fibers and in vascular smooth muscle. Cytosolic phospholipase A2 immunostaining was predominantly localized to endothelial cells of myometrial blood vessels and weakly throughout myometrial fibers. There was no apparent change in intensity of immunostaining for either isoform with gestational age or with the absence or presence of labor. CONCLUSION: The differential localization of the two phospholipase A2 isoforms suggests different functions. The apparent lack of change in expression during late gestation or with labor possibly suggests changes in myometrial phospholipase A2 activity and hence local myometrial arachidonic acid mobilization and presumably prostaglandin synthesis may not be associated with the onset of or maintenance of parturition.

Successful pregnancy after combined renal-pancreas transplantation: a case report and literature review.

A long-standing history of insulin-dependent diabetes mellitus can result in multiple organ damage. We present a case of successful pregnancy in a patient who underwent combined renal-pancreas transplantation for end-stage renal disease due to diabetic nephropathy. A 29-year-old white gravida 7, para 2 female was diagnosed with diabetes mellitus at age 7. She was well controlled with insulin until age 21. She developed complications of diabetes mellitus which included retinopathy resulting in legal blindness, nephropathy resulting in end-stage renal disease, and chronic hypertension. Following nine months of dialysis she underwent a combined renal-pancreas transplant. She subsequently became pregnant 21 months after transplantation and delivered a healthy male at 35 1/2 weeks gestation. Renal-pancreas transplant recipients who become pregnant may be at an increased risk for adverse outcome. We present a successful pregnancy outcome in a combined transplant recipient who had a prior poor obstetrical history.

Pregnancy in a combined liver and kidney transplant recipient with type 1 primary hyperoxaluria.

BACKGROUND: Little is known about pregnancy outcomes in multiple organ transplant recipients. We present a case of pregnancy in a patient after liver and kidney transplantation for the genetic disorder of type 1 primary hyperoxaluria. CASE: A 14-year-old Hispanic teenager presented with end-stage renal disease and had a kidney biopsy that revealed hyperoxaluria. A liver biopsy revealed type 1 primary hyperoxaluria. After a year of dialysis and worsening renal status, she underwent a combined orthotopic liver and kidney transplant. The patient subsequently became pregnant, but she required no antihypertensive therapy throughout the prenatal or postpartum period and showed no signs of renal or liver graft rejection. She delivered by cesarean at 38 weeks. CONCLUSION: Combined liver and kidney transplant recipients who become pregnant can have a successful outcome.