Heme Oxygenase Protects against Placental Vascular Inflammation and Abortion by the Alarmin Heme in Mice.

Both infectious as non-infectious inflammation can cause placental dysfunction and pregnancy complications. During the first trimester of human gestation, when palatogenesis takes place, intrauterine hematoma and hemorrhage are common phenomena, causing the release of large amounts of heme, a well-known alarmin. We postulated that exposure of pregnant mice to heme during palatogenesis would initiate oxidative and inflammatory stress, leading to pathological pregnancy, increasing the incidence of palatal clefting and abortion. Both heme oxygenase isoforms (HO-1 and HO-2) break down heme, thereby generating anti-oxidative and -inflammatory products. HO may thus counteract these heme-induced injurious stresses. To test this hypothesis, we administered heme to pregnant CD1 outbred mice at Day E12 by intraperitoneal injection in increasing doses: 30, 75 or 150 µmol/kg body weight (30H, 75H or 150H) in the presence or absence of HO-activity inhibitor SnMP from Day E11. Exposure to heme resulted in a dose-dependent increase in abortion. At 75H half of the fetuses where resorbed, while at 150H all fetuses were aborted. HO-activity protected against heme-induced abortion since inhibition of HO-activity aggravated heme-induced detrimental effects. The fetuses surviving heme administration demonstrated normal palatal fusion. Immunostainings at Day E16 demonstrated higher numbers of ICAM-1 positive blood vessels, macrophages and HO-1 positive cells in placenta after administration of 75H or SnMP + 30H. Summarizing, heme acts as an endogenous "alarmin" during pregnancy in a dose-dependent fashion, while HO-activity protects against heme-induced placental vascular inflammation and abortion.

Combined orthodontic, surgical, and restorative approach to treat a complicated crown-root fracture in a maxillary central incisor.

This case report shows the treatment of a severe traumatic tooth injury. For the maxillary right central incisor, the trauma was considered a complicated crown-root fracture. The level of the fracture line, the length of the remaining root segment, and the presence and condition of the tooth fragment determined the type of therapy. Traumatized teeth with fractures below the alveolar crest are often considered hopeless. As this report shows, the treatment of a complicated crown-root fracture in the esthetic region can be challenging. Orthodontic extrusion and crown-length surgery were performed to bring the fracture line above the alveolar bone crest. A multidisciplinary approach was required for complete rehabilitation of the traumatized maxillary incisor. Suggestions are made to improve treatment planning of complicated crown-root fractures.