Activation of TLR3 in the trophoblast is associated with preterm delivery.

PROBLEM: Toll-like receptors (TLRs) recognize conserved sequences on the surface of pathogens and trigger effector cell functions. Previously, we described the expression of TLR3 by human trophoblast and their ability to respond to (Poly[I:C]). Here we evaluate the effect of Poly[I:C] on mouse pregnancy and characterize the local and systemic response. METHOD OF STUDY: C57B/6 wild type (wt) and TLR3 knockout (TLR3KO) mice were treated with Poly[I:C] at 16.5 dpc and pregnancy outcome recorded. Morphologic changes, cytokines and chemokines levels in blood and utero-placental tissue were determined. NF-kappaB pathway was evaluated in vivo and in vitro. RESULTS: Poly[I:C] in C57B/6 wt mice caused preterm delivery within 24 hr (4.5 mg/kg). No effect was observed in TLR3KO mice. In addition, we observed local (placenta) and systemic (serum) response characterized by increased production of proinflammatory cytokines and chemokines. The NF-kappaB pathway was activated by Poly[I:C] in human and mice trophoblast cells. CONCLUSION: We report that Poly[I:C] induces preterm delivery via TLR3-dependent manner. Furthermore, we demonstrate that the trophoblast is able to recognize Poly[I:C] through TLR3 and respond to viral infection, modulating the immune system at the feto-maternal interface.

Sister Mary Joseph's nodule as the first sign of pregnancy-associated gastric cancer: a case report.

Sister Mary Joseph's nodule is an inconspicuous and uncommon clinical sign of advanced malignant disease, especially gastric cancer. Pregnancy-associated gastric cancer is an extremely rare condition and can be difficult to diagnose, due to the absence or misinterpretation of symptoms as pregnancy-related. Diagnostic aids, such as a basic chemistry panel and imaging techniques, may not show any abnormalities. We present a case of a 37-year-old pregnant patient whose umbilical nodule was the first presenting physical sign of gastric cancer, which had metastasized throughout the abdominal and pelvic regions.

Supporting the hypothesis of pregnancy as a tumor: survivin is upregulated in normal pregnant mice and participates in human trophoblast proliferation.

PROBLEM: Survivin, a tumor-promoting antiapoptotic molecule, is expressed in the human placenta. Here, we analyzed its expression during normal and pathological murine pregnancy and investigated its participation in human first trimester trophoblast cell survival and proliferation. METHOD OF STUDY: We first analyzed the expression of survivin on the mRNA and protein level at the fetal-maternal interface of normal pregnant (CBA/J x BALB/c) and abortion-prone (CBA/J x DBA/2J) mice at different pregnancy stages by RT-PCR and immunohistochemistry. We also evaluated apoptosis in murine trophoblasts in both mating combinations by TUNEL technique. Functional studies were carried out by knockdown survivin by means of siRNA methodology in two human first trimester trophoblast cell lines [Swan.71 (Sw.71) and HTR8 (H8)]. RESULTS: We observed a peak in mRNA levels on day 5 and a peak of protein levels on day 8 of pregnancy in both combinations. The level of survivin in animals from the abortion-prone group was decreased compared with normal pregnant mice on day 8, which was accompanied by elevated apoptosis rates. In later pregnancy stages (days 10 and 14), survivin levels decreased to levels comparable to those observed right after fecundation in both groups. Transfection of human first trimester cell lines (H8 and Sw.71) with siRNA targeting the survivin gene led to a 76-82% reduction of its expression leading to reduced trophoblast cell viability and proliferation. CONCLUSION: Our findings suggest an important role of survivin to promote trophoblast cell survival and proliferation during placentation, thus maintaining pregnancy. The pregnancy-associated expression of a cancer molecule such as survivin supports the 'pseudo-malignancy' hypothesis of pregnancy. Our data may contribute to the better understanding of trophoblast cell development during implantation and placentation.

Quality and stability of red cells derived from gravity-separated placental blood with a hollow-fiber system.

BACKGROUND: Several studies show that donor red blood cells (RBCs) can be processed by gravity separation with a hollow-fiber filtration system. This study investigated whether fetal blood could be filtered in the same way. STUDY DESIGN AND METHODS: Twelve newborns born after healthy pregnancies were included in the study. Placental blood was sampled with standard procedures. The sampled blood was separated with a specially designed hollow-fiber filtration system (Sangofer neonatal, Heim Group). The RBC bag contained 10 mL of saline, adenine, glucose-mannitol (SAG-M) for stabilization. After processing, the resulting RBC volume was estimated. Quality variables (blood counts, hemolysis rate) were measured before and after 35 days of storage at +4 degrees C. RESULTS: The 12 processed RBC units had a mean volume of 62.3 +/- 13.5 mL and a mean hematocrit level of 0.56 +/- 0.06. No white blood cell contamination could be detected in any of the RBC units tested. After 35 days of storage, the hemolysis was 0.1 +/- 0.07 and the amount of free hemoglobin was 0.28 +/- 0.017 mmol per L. CONCLUSIONS: This study shows that it is possible to process placental blood to RBCs by gravity separation with a hollow-fiber system. The quality of the RBCs thus processed was suitable for 35 days storage. The use of placental blood in the treatment of children with anemia (e.g., malaria) in the underresourced world is widely discussed. Because the separation device used here needs no additional equipment or electrical devices, it is considered to be an ideal method for use in these countries.

Lethal candida sepsis associated with myeloperoxidase deficiency and pre-eclampsia.

We report on a 27-year-old primipara suffering from pre-eclampsia who died within 2 days postpartum. Toxemia with disseminated intravascular coagulation (DIC) and acute renal failure had masked the symptoms of invasive candida esophagitis and disseminated candidiasis in both lungs. Candida sepsis was discovered as the cause of death at postmortem examination. Myeloperoxidase (MPO) deficiency was identified as having supported the invasive candida infection. We conclude that a combination of MPO-deficiency and gestational toxemia may indicate increased susceptibility to severe candida infections.