Molar-incisor hypomineralisation in Norwegian children: Prevalence and associated factors.

This study investigated the prevalence and associations of molar-incisor hypomineralisation (MIH) in 8-9 year-old children in Oslo. A total of 3013 children in one age cohort participated in the study during their regular dental examination at the Public Dental Service. Hypomineralised enamel defects were recorded according to the European Academy of Paediatric Dentistry criteria for MIH. Information on health and medications used during pregnancy and in the child's first 3 years of life was obtained from a questionnaire administered to parents. The overall prevalence of MIH was 28.2%, with no gender difference. A higher prevalence of MIH was found in children who had been ill or had used medication in early life and in those whose mother had been ill during pregnancy. No association was found between MIH and prematurity or maternal use of medication during pregnancy. The multivariable analyses showed that children with MIH were more likely to have suffered from illness in early life (OR = 1.41, 95% CI: 1.17-1.70), used antibiotics during the first year of life (OR = 1.68, 95% CI: 1.19-2.35), experienced tooth pain (OR = 1.33, 95% CI: 1.03-1.72), and experienced pain while toothbrushing (OR = 2.17, 95% CI: 1.46-3.23) than children without MIH. The prevalence of MIH was high in the children participating in this study.

Lysophosphatidic acid induces both EGFR-dependent and EGFR-independent effects on DNA synthesis and migration in pancreatic and colorectal carcinoma cells.

Lysophosphatidic acid (LPA) is a small glycerophospholipid ubiquitously present in tissues and plasma. It acts through receptors belonging to the G-protein-coupled receptor (GPCR) family, is involved in several biological processes, and is strongly implicated in different cancers. In this paper, we have investigated the effects of LPA on DNA synthesis and migration in a panel of pancreatic and colon cancer cells, with particular focus on the involvement of the epidermal growth factor (EGF) receptor (EGFR) in LPA-induced signaling. LPA stimulated DNA synthesis and/or migration in all the cell lines included in this study. In five of the six cell lines, LPA induced phosphorylation of the EGFR, and the effects on EGFR and Akt, and in some of the cells also ERK, were sensitive to the EGFR tyrosine kinase inhibitor gefitinib, strongly suggesting LPA-induced EGFR transactivation in these cells. In contrast, in one of the pancreatic carcinoma cell lines (Panc-1), we found no evidence of transactivation of the EGFR. In the pancreatic carcinoma cell lines where transactivation took place (BxPC3, AsPC1, HPAFII), gefitinib reduced LPA-induced DNA synthesis and/or migration. However, we also found evidence of transactivation in the two colon carcinoma cell lines (HT29, HCT116) although gefitinib did not inhibit LPA-induced DNA synthesis or migration in these cells. Taken together, the data indicate that in many gastrointestinal carcinoma cells, LPA uses EGFR transactivation as a mechanism when exerting such effects as stimulation of cell proliferation and migration, but EGFR-independent pathways may be involved instead of, or in concerted action with, the EGFR transactivation.

Molar-Incisor Hypomineralisation: Severity, caries and hypersensitivity.

OBJECTIVES: To investigate distribution of affected teeth and severity of molar-incisor hypomineralisation (MIH) in 8-9-year-old children. A second aim was to study association between severity of MIH and hypersensitivity, caries, and affection of incisors and second primary molars (SPM). METHODS: A total of 3013 children in one age cohort participated in a cross-sectional study, of which 851 children were diagnosed with MIH. A majority of these children were re-examined and MIH diagnosis based on the European Academy of Paediatric Dentistry criteria was confirmed in 538 children. The re-examinations were undertaken at the local clinics by one calibrated dentist. Data were tested with bivariate logistic regression analysis. Results were reported using frequencies, proportions, odds ratios (OR) and confidence intervals (CI). RESULTS: Almost half of the children with MIH (46.8 %) had at least one severely affected molar. Incisors were affected in 51.9 % of children with MIH, and the prevalence was higher in children with severe affection (57.4 %, p < 0.01). Among children with MIH, second primary molars were affected in 29.6 %, hypersensitivity in at least one first permanent molar was reported by 25.8 and 30.8 % had caries extending to dentine. Children classified with severe MIH were more likely to suffer from hypersensitivity (OR 5.62, 95 % CI 3.61-8.74) and dentine caries (OR 10.32, 95 % CI 6.46-16.50) than children with mild MIH. CONCLUSION: Prevalence of hypomineralised incisors and SPM were high in the studied children with MIH. Children with severe MIH had higher probability of incisor affection, dentin caries and hypersensitivity. CLINICAL SIGNIFICANCE: This study highlights the importance of understanding the association between MIH, caries and hypersensitivity, especially in children with severe MIH. These children need extensive and individualized care in the dental services to prevent caries and pain.

Molar incisor malformation in six cases: description and diagnostic protocol.

OBJECTIVE: The term molar-incisor malformation (MIM) has recently been presented in the scientific literature, where it is described as a condition with localized impaired root development. Here we present 6 recently discovered cases referred to our departments. STUDY DESIGN: The patients were enrolled in the study after referral and were examined clinically and radiologically. Two extracted teeth were further examined with micro-computed tomography or microscopy. RESULTS: Affected teeth were first permanent molars with hypoplastic roots, narrow pulp chambers, and a hypercalcified dentine layer cervical to the pulp chamber. Two of the cases also had cervical constrictions on the upper incisors. The patients were 8 to 12 years of age and healthy, but had experienced serious medical conditions of the head and neck region in their first year of life. Some of the cases had been referred because of acute infection and pain. CONCLUSION: In 5 out of 6 patients, severe health problems in the head and neck region early in life may have been associated with root malformation in molars and incisors. Patients with MIM need to be followed closely, and extractions should be planned at the right time to avoid unnecessary infection and pain in addition to orthodontic problems.

The TGFß-SMAD3 pathway inhibits IL-1α induced interactions between human pancreatic stellate cells and pancreatic carcinoma cells and restricts cancer cell migration.

BACKGROUND: The most abundant cells in the extensive desmoplastic stroma of pancreatic adenocarcinomas are the pancreatic stellate cells, which interact with the carcinoma cells and strongly influence the progression of the cancer. Tumor stroma interactions induced by IL-1α/IL-1R1 signaling have been shown to be involved in pancreatic cancer cell migration. TGFß and its receptors are overexpressed in pancreatic adenocarcinomas. We aimed at exploring TGFß and IL-1α signaling and cross-talk in the stellate cell cancer cell interactions regulating pancreatic adenocarcinoma cell migration. METHODS: Human pancreatic stellate cells were isolated from surgically resected pancreatic adenocarcinomas and cultured in the presence of TGFß or pancreatic adenocarcinoma cell lines. The effects of TGFß were blocked by inhibitors or amplified by silencing the endogenous inhibitor of SMAD signaling, SMAD7. Pancreatic stellate cell responses to IL-1α or to IL-1α-expressing pancreatic adenocarcinoma cells (BxPC-3) were characterized by their ability to stimulate migration of cancer cells in a 2D migration model. RESULTS: In pancreatic stellate cells, IL-1R1 expression was found to be down-regulated by TGFß and blocking of TGFß signaling re-established the expression. Endogenous inhibition of TGFß signaling by SMAD7 was found to correlate with the levels of IL-1R1, indicating a regulatory role of SMAD7 in IL-1R1 expression. Pancreatic stellate cells cultured in the presence of IL-1α or in co-cultures with BxPC-3 cells enhanced the migration of cancer cells. This effect was blocked after treatment of the pancreatic stellate cells with TGFß. Silencing of stellate cell expression of SMAD7 was found to suppress the levels of IL-1R1 and reduce the stimulatory effects of IL-1α, thus inhibiting the capacity of pancreatic stellate cells to induce cancer cell migration. CONCLUSIONS: TGFß signaling suppressed IL-1α mediated pancreatic stellate cell induced carcinoma cell migration. Depletion of SMAD7 upregulated the effects of TGFß and reduced the expression of IL-1R1, leading to inhibition of IL-1α induced stellate cell enhancement of carcinoma cell migration. SMAD7 might represent a target for inhibition of IL-1α induced tumor stroma interactions.