losartan-potassium and Cholestasis--Intrahepatic

Infant respiratory distress syndrome (iRDS) in babies born from women with intrahepatic cholestasis of pregnancy (ICP) has been associated with intrauterine exposure to high bile acid levels. Here, we have investigated the role of macrophages in hypercholanemia-induced changes in maternal and fetal lung. Obstructive cholestasis in pregnant rats (OCP) was maintained from day 14 of gestation to term. Gene expression was determined by RT-QPCR, Western blot, and immunofluorescence. The maternal-fetal bile acid pool was radiolabelled using [(3)H]-taurocholate. OCP resulted in increased bile acids in maternal and fetal organs, including lungs. This was accompanied by structural changes in lung tissue, more marked in fetuses (peribronchial edema, collapse of alveolar spaces and deposits of hyaline material in the alveolar lumen), and infiltration of lung tissue by inflammatory cells. The abundance of macrophages and neutrophils in bronchoalveolar lavage fluid (BALF) was also increased in OCP group. Phospholipase A2-IIA (PLA2), the key enzyme in surfactant degradation, was mainly immunodetected in macrophages, which also expressed the bile acid receptor TGR5. The overall expression of PLA2 was markedly enhanced in maternal and fetal lungs of OCP group and in control maternal BALF cells incubated with bile acids. In neonates born from OCP mothers, the enhanced expression of erythropoietin suggested the presence of hypoxia due to iRDS. In conclusion, these results indicate that the accumulation of bile acids due to maternal cholestasis triggers an inflammatory response in the maternal and fetal lungs together with enhanced macrophage-associated PLA2 expression, which may play an important role in iRDS development.. Maternal cholestasis causes respiratory distress syndrome in rat neonates. Cholestasis in pregnant rats causes bile acid accumulation in the fetal lung. This induces lung macrophages infiltration and inflammatory response. Alveolar macrophages co-express phospholipase A2-IIA and TGR5, but not FXR. Bile acid accumulation stimulates phospholipase A2-IIA, but not TGR5, expression.

Topics: Animals; Bile Acids and Salts; Carrier Proteins; Cholestasis, Intrahepatic; Erythropoietin; Female; Fetus; Gene Expression; Humans; Liver; Lung; Macrophages; Peroxidase; Phospholipases A2; Pneumonia; Pregnancy; Pregnancy Complications; Rats, Wistar; Receptors, Cytoplasmic and Nuclear; Receptors, G-Protein-Coupled; Respiratory Distress Syndrome, Newborn

A postnatal hyporegenerative anemia may complicate Rh hemolytic disease. Intramedullary hemolysis, bone marrow suppression, and erythropoietin deficiency have been implicated etiologically. Treatment with recombinant erythropoietin (r-EPO) has yielded encouraging preliminary results. The authors describe an infant with Rh isoimmunization who developed severe hyporegenerative anemia unresponsive to a 5-week course of r-EPO. Two additional doses at 12 weeks resulted in brisk reticulocytosis, coinciding with a 16-fold decline in the anti-Rh(D) antibody titer. Thus, treatment with r-EPO may be ineffective when anti-Rh(D) antibody titers are high. The authors also show that erythropoietin deficiency in hyporegenerative anemia is not as frequent and severe as originally thought.

Topics: Adult; Anemia; Blood Transfusion, Intrauterine; Cholestasis, Intrahepatic; Drug Resistance; Erythroblastosis, Fetal; Erythrocyte Transfusion; Erythropoiesis; Erythropoietin; Female; Ferritins; Hepatomegaly; Humans; Immunity, Maternally-Acquired; Infant, Newborn; Iron Overload; Isoantibodies; Jaundice, Neonatal; Phototherapy; Pregnancy; Recombinant Proteins; Reticulocyte Count; Rh Isoimmunization; Rho(D) Immune Globulin; Time Factors

To investigate the cause of fetal asphyxia of mothers with intrahepatic cholestasis of pregnancy (ICP).. The cord plasma erythropoietin (EPO) concentrations were measured in 37 infants of mothers with ICP and 46 control infants after elective cesarean section. Furthermore, the transfer of oxygen across the placental membranes in ICP group (n = 7) were compared with controls (n = 8) by dual perfusion of the human placental lobule in vitro.. The oxygen transfer across the placental membrane in ICP was similar to the controls (P < 0.05). However cord venous EPO was lower in infants delivered by elective cesarean section from women with ICP (13.58 +/- 8.88 IU/L, P < 0.05) than that in control infants (20.43 +/- 14.15 IU/L).. The transfer of oxygen across the placental membrane in ICP may be normal. The lower cord venous EPO value in ICP may be mainly responsible for the fetal asphyxia.

Topics: Adult; Asphyxia Neonatorum; Cholestasis, Intrahepatic; Erythropoietin; Female; Fetal Blood; Humans; Infant, Newborn; Pregnancy; Pregnancy Complications