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.
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.
•A maxillary right central incisor had a complicated crown-root fracture.•Teeth with fractures below the alveolar crest are often considered hopeless.•Orthodontic extrusion and crown-length surgery shifted the fracture line.•The tooth was eventually restored with a crown.
Cranial neural crest cells (CNCCs), identified by expression of transcription factor Sox9, migrate to the first branchial arch and undergo proliferation and differentiation to form the cartilage and ...bone structures of the orofacial region, including the palatal bone. Sox9 promotes osteogenic differentiation and stimulates CXCL12-CXCR4 chemokine-receptor signaling, which elevates alkaline phosphatase (ALP)-activity in osteoblasts to initiate bone mineralization. Disintegration of the midline epithelial seam (MES) is crucial for palatal fusion. Since we earlier demonstrated chemokine-receptor mediated signaling by the MES, we hypothesized that chemokine CXCL12 is expressed by the disintegrating MES to promote the formation of an osteogenic center by CXCR4-positive osteoblasts. Disturbed migration of CNCCs by excess oxidative and inflammatory stress is associated with increased risk of cleft lip and palate (CLP). The cytoprotective heme oxygenase (HO) enzymes are powerful guardians harnessing injurious oxidative and inflammatory stressors and enhances osteogenic ALP-activity. By contrast, abrogation of HO-1 or HO-2 expression promotes pregnancy pathologies. We postulate that Sox9, CXCR4, and HO-1 are expressed in the ALP-activity positive osteogenic regions within the CNCCs-derived palatal mesenchyme. To investigate these hypotheses, we studied expression of Sox9, CXCL12, CXCR4, and HO-1 in relation to palatal osteogenesis between E15 and E16 using (immuno)histochemical staining of coronal palatal sections in wild-type (wt) mice. In addition, the effects of abrogated HO-2 expression in HO-2 KO mice and inhibited HO-1 and HO-2 activity by administrating HO-enzyme activity inhibitor SnMP at E11 in wt mice were investigated at E15 or E16 following palatal fusion. Overexpression of Sox9, CXCL12, CXCR4, and HO-1 was detected in the ALP-activity positive osteogenic regions within the palatal mesenchyme. Overexpression of Sox9 and CXCL12 by the disintegrating MES was detected. Neither palatal fusion nor MES disintegration seemed affected by either HO-2 abrogation or inhibition of HO-activity. Sox9 progenitors seem important to maintain the CXCR4-positive osteoblast pool to drive osteogenesis. Sox9 expression may facilitate MES disintegration and palatal fusion by promoting epithelial-to-mesenchymal transformation (EMT). CXCL12 expression by the MES and the palatal mesenchyme may promote osteogenic differentiation to create osteogenic centers. This study provides novel evidence that CXCL12-CXCR4 interplay facilitates palatal osteogenesis and palatal fusion in mice.
Orthodontic forces disturb the microenvironment of the periodontal ligament (PDL), and induce craniofacial bone remodeling which is necessary for tooth movement. Unfortunately, orthodontic tooth ...movement is often hampered by ischemic injury and cell death within the PDL (hyalinization) and root resorption. Large inter-individual differences in hyalinization and root resorption have been observed, and may be explained by differential protection against hyalinization. Heme oxygenase-1 (HO-1) forms an important protective mechanism by breaking down heme into the strong anti-oxidants biliverdin/bilirubin and the signaling molecule carbon monoxide. These versatile HO-1 products protect against ischemic and inflammatory injury. We postulate that orthodontic forces induce HO-1 expression in the PDL during experimental tooth movement. Twenty-five 6-week-old male Wistar rats were used in this study. The upper three molars at one side were moved mesially using a Nickel-Titanium coil spring, providing a continuous orthodontic force of 10 cN. The contralateral side served as control. After 6, 12, 72, 96, and 120 h groups of rats were killed. On parasagittal sections immunohistochemical staining was performed for analysis of HO-1 expression and quantification of osteoclasts. Orthodontic force induced a significant time-dependent HO-1 expression in mononuclear cells within the PDL at both the apposition- and resorption side. Shortly after placement of the orthodontic appliance HO-1 expression was highly induced in PDL cells but dropped to control levels within 72 h. Some osteoclasts were also HO-1 positive but this induction was shown to be independent of time- and mechanical stress. It is tempting to speculate that differential induction of tissue protecting- and osteoclast activating genes in the PDL determine the level of bone resorption and hyalinization and, subsequently, "fast" and "slow" tooth movers during orthodontic treatment.
Disintegration of the midline epithelial seam (MES) is crucial for palatal fusion, and failure results in cleft palate. Palatal fusion and wound repair share many common signaling pathways related to ...epithelial-mesenchymal cross-talk. We postulate that chemokine CXCL11, its receptor CXCR3, and the cytoprotective enzyme heme oxygenase (HO), which are crucial during wound repair, also play a decisive role in MES disintegration. Fetal growth restriction and craniofacial abnormalities were present in HO-2 knockout (KO) mice without effects on palatal fusion. CXCL11 and CXCR3 were highly expressed in the disintegrating MES in both wild-type and HO-2 KO animals. Multiple apoptotic DNA fragments were present within the disintegrating MES and phagocytized by recruited CXCR3-positive wt and HO-2 KO macrophages. Macrophages located near the MES were HO-1-positive, and more HO-1-positive cells were present in HO-2 KO mice compared to wild-type. This study of embryonic and palatal development provided evidence that supports the hypothesis that the MES itself plays a prominent role in palatal fusion by orchestrating epithelial apoptosis and macrophage recruitment via CXCL11-CXCR3 signaling.
This article is a 6-year posttreatment follow-up of a 28-year-old woman who suffered severe traumatic dental injury, including a complicated crown-root fracture of the maxillary right central ...incisor. The trauma resulted in periodontal pathology, including a periodontal pocket and fistula on the palatal side and external inflammatory root resorption in the area of the subgingival fracture line. A multidisciplinary treatment, including endodontic treatment, orthodontic extrusion, crown-length surgery, and prosthetic treatment, was required for complete rehabilitation of the traumatized maxillary incisor. Good anatomic proportions and optimal hard and soft-tissue esthetics without periodontal pathology were achieved long-term.
To investigate whether use of adalimumab decreases the frequency of attacks of anterior uveitis (AU) in patients with ankylosing spondylitis (AS).
Consecutive patients with AS, visiting an outpatient ...clinic and treated for at least 12 weeks with adalimumab, were enrolled. The number of attacks of AU in the year before start and during treatment were assessed by patient history and ophthalmological controls.
In the 77 patients a total of 52 AU attacks occurred in the year before baseline (68 attacks per 100 patient-yrs), whereas during adalimumab treatment 19 attacks were seen (14 per 100 patient-yrs; reduction rate 80%). Twenty-six patients with AU in the year before start of adalimumab treatment had recurrent attacks, with a median number of 2.0 AU attacks per year interquartile range (IQR) 1.00-3.00, whereas during treatment this decreased to 10 patients with a median number of 0.56 attacks per year (IQR 0.30-0.75). Hence, the number of attacks per year decreased by 72% (p = 0.000).
In patients with AS, a significant reduction in the number of AU attacks, as well as in the number of attacks per patient, was observed during adalimumab treatment.
Mechanical ventilation (MV) is a life-saving intervention in acute respiratory failure without any alternative. However, even protective ventilation strategies applying minimal mechanical stress may ...evoke ventilator-induced lung injury (VILI). Adjuvant pharmacological strategies in addition to lung-protective ventilation to attenuate VILI are lacking. Adrenomedullin exhibited endothelial barrier-stabilising properties in vitro and in vivo.
In untreated mice (female C57/Bl6 mice, 11-15 weeks old) and animals treated with adrenomedullin, lung permeability, local and systemic inflammation and markers of distal organ function were assessed following 2 or 6 h of mechanical ventilation with 100% oxygen and protective or moderately injurious ventilator settings, respectively.
Adrenomedullin dramatically reduced lung permeability in VILI in mice, leading to improved oxygenation. Adrenomedullin treatment reduced myosin light chain phosphorylation, attenuated the accumulation of leucocytes in the lung and prevented the increase in lactate and creatinine levels in mice ventilated with high tidal volumes. Moreover, adrenomedullin protected against VILI even when treatment was initiated 2 h after the beginning of mechanical ventilation in a 6 h VILI mouse model.
Adjuvant treatment with adrenomedullin may be a promising new pharmacological approach to attenuate VILI.
Introduction Accurate articulation of the digital dental casts is crucial in orthodontic diagnosis and treatment planning. We aimed to determine the accuracy of manufacturing digital dental casts ...from computed tomography scanning of plaster casts regarding linear dimensions and interarch relationships and to test whether eventual differences in interarch relationships between plaster and digital casts would affect orthodontic diagnostics. Methods Plaster casts with the wax bites of 2 patients were used to create digital dental casts with a computed tomography scanner. This was repeated 4 times with a 1-week interval. Linear distances were measured on plaster and digital models twice by 2 observers. Next, the 4 digital models of each patient were scored twice by 5 observers for interarch variables. Results Digital vs plaster measurements showed high Pearson correlation coefficients (>0.954), whereas the mean difference was small (<0.1 mm) and not significant. The interarch scorings, however, showed significant differences for all variables, except overjet for model 1. Conclusions We found substantial interarch inaccuracies of the digital models. These inaccuracies are probably due to a lack of built-in “collision control” in the software and manual articulation of the digital models by a human operator.
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