Alginates induce differentiation and expression of CXCR7 and CXCL12/SDF-1 in human keratinocytes-The role of calcium

Alginates from seaweed are used in chronic wound management, though the molecular and cellular effects of various alginate dressings are not well documented. We have developed ultrapure sodium-alginates from Pseudomonas fluorescens with different content and distribution of single guluronic acid (G) residues (0-45% G), and tested their biological activities on human primary keratinocytes (KCs). The alginates inhibited KC migration and induced expression of differentiation markers. The potency of the alginates correlated with the increasing percentage of single G residues. These findings were explained by different binding and release of ionic calcium (Ca++) from the alginates which subsequently triggered differentiation. Ca-free alginates had no effect on KC migration and differentiation, but the chemokine receptor CXCR7 was upregulated. Q-PCR revealed that also CXCL12/SDF-1, one of two known CXCR7-ligands, was induced by the alginates. Both CXCR7 and CXCL12-induction was dependent on the alginate G-content, and highest upregulation was induced by an alginate with 19% single G residues. In the epidermis, CXCR7 expression was restricted to the basal layer. This study defines two biological effects of ultrapure alginates on KCs, both being dependent on the alginate structure, and being either dependent or independent of Ca. ? 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 100A:2803-2812, 2012.     

Reproducibility of tumour typing of lung carcinomas performed according to WHO's recommendation

Tumour sections from 139 patients with bronchial carcinoma were classified blindly by a panel of three pathologists according to the WHO recommendation of 1981. Only sections from resected specimens were included. There was agreement among all reviewers with regard to the main WHO tumour type of 71% of the specimens. For the remainder, two reviewers agreed upon 19% whereas the tumour classification differed substantially in 10% of all cases. About half of the original diagnoses were maintained when the latter group was re-evaluated blindly. Best agreement in the whole material was noted for squamous cell carcinoma. The main difficulty was differentiation between adenocarcinoma and squamous cell carcinoma with a high malignancy grading score. Despite the improvements of the WHO classification system, our group of diagnostic problem cases was not reduced when compared with earlier classification studies.     

Protein adsorption to hydroxyapatite and to calcium fluoride in vitro and amino acid analyses of pellicle formed on normal enamel and on calcium-fluoride-covered enamel in vivo

Fluoride treatment of enamel has been reported to result in the formation of a layer of a CaF2-like material on the enamel surface. Protein adsorption to enamel is a specific process dependent on the nature of the surface, and little is known about protein adsorption to CaF2. Albumin and lysozyme were adsorbed to hydroxyapatite (HA) and CaF2 powder in vitro, and protein adsorption patterns constructed. In vivo pellicle was collected from three volunteers from fluoride-treated enamel and from normal enamel, and the amino acid compositions analyzed separately. The results showed that CaF2 took up small amounts of proteins as compared with HA. When the CaF2 was pretreated with a phosphate buffer, pH 6.8, the protein adsorption increased markedly. The amino acid analyses showed no major differences in the amino acid compositions between pellicle collected from CaF2-covered enamel and pellicle collected from normal enamel. This lack of difference is presumably due to the adsorption of phosphate ions to the CaF2 crystals and hence changed surface properties.     

Cleft lip and palate versus cleft lip only: are they distinct defects?

Cleft lip defects are usually regarded as a single entity, with the assumption that an accompanying cleft palate represents the more severe form. The authors linked data from the Medical Birth Registry of Norway with medical records from two centralized centers to provide a population-based data set. They assessed the distribution of cleft lip only and cleft lip with cleft palate by covariate. Among 1.8 million Norwegian livebirths between 1967 and 1998, there were 1,572 cases of cleft lip with cleft palate and 1,122 cases with cleft lip only. Seventeen percent of those with cleft lip and palate had another defect compared with 9% of those with cleft lip only. For boys, the risk was greater for cleft lip and palate than for cleft lip only (odds ratio=2.4 vs. 1.8, p<0.001 for difference). The risk of cleft lip only, but not of cleft lip and palate, was increased for twins (odds ratio=1.6 vs. 1.1, p=0.11) and infants whose parents were first cousins (odds ratio=2.7 vs. 0.7, p=0.07). Although cleft lip with cleft palate may simply represent a more severe form of the defect, epidemiologic assessments of cleft lip should, when possible, include separate analyses of these two groups.     

Severe jaundice in early IVF pregnancy

Jaundice in early pregnancy after in vitro fertilization (IVF) is extremely rare. We report a case of severe jaundice in an IVF treated patient, with a clinical picture similar to intrahepatic cholestasis of pregnancy (ICP). We suggest strategies to prevent similar cases in the future.     

Is pre-eclampsia more than one disease?

OBJECTIVES: The clinical characteristics of pre-eclampsia (gestational hypertension and proteinuria) may represent separate pathogenetic conditions. Pre-eclampsia accompanied by restricted fetal growth may originate from abnormal implantation, and appropriate or high birthweights may indicate a mixture of conditions, ranging from mild pre-eclampsia with modest placental involvement to hypertensive conditions without placental disease. DESIGN: Prospective, observational study. SETTING: General population. POPULATION: We used data from the Medical Birth Registry of Norway, a population-based registry that has recorded births since 1967. For this study, we used information on length of gestation and presence of pre-eclampsia among 1,679,205 singletons born between 1967 and 1998. Pre-eclampsia was diagnosed in 44,220 (2.6%) pregnancies. METHODS: We studied the risk of pre-eclampsia in relation to standardised measures (z scores) of birthweight, adjusted for length of gestation, and stratified by term and preterm delivery. We also explored whether gestational diabetes was more prevalent in conjunction with preterm than term pre-eclampsia. MAIN OUTCOME MEASURES: Pre-eclampsia diagnosed at term or preterm. RESULTS: For pre-eclampsia diagnosed around term, there was a U-shaped association with birthweight. Compared with appropriate birthweights for gestation, the risk of term pre-eclampsia was more than fourfold higher (relative risk [RR] 4.5, 95% confidence interval [CI], 4.3 to 4.7) if the baby's birthweight was lower than two standard deviations under the mean. For birthweights three standard deviations or higher than the mean, pre-eclampsia was more than twice as likely (RR 2.6, 95% CI 2.2-2.9). In contrast, the risk of preterm pre-eclampsia displayed an L-shaped association with birthweight. Low birthweight (less than -2 standard deviations) was associated with greatly increased risk (RR 9.9, 95% CI 9.1-10.9), but for high birthweights (>or=3 standard deviations), there was no association with the risk of preterm pre-eclampsia (RR 1.2, 95% CI 0.7-2.1). The prevalence of gestational diabetes was three times (prevalence ratio 3.3, 95% CI 2.6-3.6) higher in preterm than term pre-eclampsia. CONCLUSION: Whereas pre-eclampsia with preterm delivery associated with low birthweight may be caused by underlying placental abnormality, pre-eclampsia delivered at term may represent a mixture of conditions, ranging from mild pre-eclampsia with moderate placental affection to hypertensive conditions in pregnancy without placental dysfunction.     

Molecular weight dependency on the production of the TNF stimulated by fractions of rye (1-->3),(1-->4)-beta-D-glucan

Mixed-linkage (1-->3),(1-->4)-beta-D-glucan with a weight average molecular weight varying between 79,800 and 13,900 was purified from rye. These fractions were used for stimulation of human monocytes to produce tumour necrosis factor (TNF). A mixed-linkage beta-glucan with a weight average molecular weight of 18,900 was found to be the most potent immunostimulator.