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Abstract: Purpose: Tissue engineering is a new way to regenerate bone tissue, where osteogenic capable cells combine with an appropriate scaffolding material. Our aim was in a Medline Search to evaluate osteoblast mineralization in vitro and in vivo including gene expressing combining mesenchymal stem cells (MSCs) and five different carriers, titanium, collagen, calcium carbonate, calcium phosphate and polylactic acid-polyglycolic acid copolymer for purpose of a meta—or a descriptive analysis. Materials and methods: The search included the following MeSH words in different combinations—mesenchymal stem cells, alkaline phosphatase, bone regeneration, tissue engineering, drug carriers, tissue scaffolds, titanium, collagen, calcium carbonate, calcium phosphates and polylactic acid-polyglycolic acid copolymer. Results: Two out of 80 articles included numerical values and as control, carriers and cells, on mineralization and gene expression. β-tricalcium phosphate (β-TCP) revealed elevated alkaline phosphatase activity, and calcium-deficient hydroxyapatite a greater gene expression of osteocalcin when seeded with induced MSCs. Conclusion: No data are published on titanium used as a carrier in MSC osteoblast mineralization. A meta- as well as a descriptive analysis includes numerical values of test materials and of control reactions from carrier and cells, respectively. Only two articles fulfilled these requirements. [Copyright &y& Elsevier]

Summary: Dominant mutations in the surfactant protein-C(SFTPC) gene have been linked with interstitial lung disease. The frequency of lung disease due to SFTPC mutations in the general population is unknown. The aim of this study was to identify novel SFTPC mutations that are associated with lung function or disease in the general population. We resequenced the SFTPC gene in 760 individuals and identified 18 genetic variants, of which 5 were novel. Of the five novel mutations, two were situated in highly conserved areas of the SFTPC gene: A53T and Y106X. We genotyped the Copenhagen City Heart Study(n =10,604) and the Copenhagen General Population Study(n =37,337) to assess the clinical relevance of these mutations. Genotyping identified 36 individuals heterozygous for A53T and 3 individuals heterozygous for Y106X. A53T heterozygotes and Y106X heterozygotes did not differ from non-carriers in FEV1% predicted, FVC% predicted or FEV1/FVC. A53T heterozygotes had a two-fold increased risk for asthma in the Copenhagen City Heart Study and Copenhagen General Population Study combined (adjusted odds ratio 2.2(1.0–4.9)). A53T heterozygotes did not differ consistently from non-carriers in risk of chronic obstructive pulmonary disease or interstitial lung disease. No Y106X heterozygotes suffered from asthma, chronic obstructive pulmonary disease (COPD), or interstitial lung disease. We identified two novel mutations in highly conserved areas of the SFTPC gene, and show that heterozygotes for the mutations have normal lung function and are unaffected by COPD and interstitial lung disease. A53T heterozygotes had increased asthma risk, but further research is required to conclusively determine whether this mutation is associated with asthma. [Copyright &y& Elsevier]

Summary: The angiotensin-converting enzyme (ACE) gene is a potential candidate gene for risk of asthma, COPD, and COPD co-morbidity. In 9034 Danish adults, we determined whether individuals homozygous or heterozygous for the ACE D allele are at greater risk of asthma, COPD, or COPD co-morbidity compared with ACE II homozygous individuals. In the general population, serum ACE activity increased with the number of D alleles (Kruskal-Wallis ANOVA: II vs. ID, p <0.001; ID vs. DD, p <0.001); however, this did not translate into altered risk of asthma or COPD. In the general population, the odds ratio (95% confidence interval) for asthma was 1.2 (0.9–1.4) for ID individuals and 1.2 (0.9–1.5) for DD individuals compared with II individuals. In the general population, the odds ratio for COPD was 0.9 (0.8–1.1) for ID individuals and 1.0 (0.8–1.2) for DD individuals compared with II individuals. Among patients with COPD, the odds ratio for ischemic heart disease was 1.1 (0.8–1.6) for ID individuals and 1.2 (0.8–1.7) for DD individuals compared with II individuals; corresponding odds ratios for hypertension were 1.1 (0.7–1.5) and 0.8 (0.5–1.2), and for low physical activity 0.9 (0.5–1.4) and 0.7 (0.4–1.2). The results were similar upon adjustment for sex, age, smoking status, body mass index, total cholesterol, and ACE inhibitor/angiotensin II type 1 receptor blocker use. These data suggest that lifelong genetically elevated ACE activity is not a major risk factor for asthma or COPD, or for ischemic heart disease, hypertension, and low physical activity in COPD patients. [Copyright &y& Elsevier]

Abstract: Purpose: Adipose derived mesenchymal stem cells (ADMSCs) may be osteogenic, may generate neoangiogenisis and may be progenitors for differentiated osteoblast mineralization. Titanium granules may be suitable as carriers for these cells. The aim was to demonstrate the osteogenic potential of ADMSCs and the effect of porous non-oxidized (Ti) and oxidized titanium (TiO2) granules as carriers for ADMSCs mineralization in vitro. Materials and methods: ADMSCs were isolated, cultivated in osteoblast medium and evaluated for alkaline phosphatase (ALP) assay, RNA isolation, and ALP staining. Osteoblast in vitro mineralization cells without granules or seeded on Ti or TiO2 granules were evaluated for Alizarin Red assay and RNA isolation for later gene expressing. Results: ADMSCs express osteoblastic lineage genes, CBFA-1 and stain strongly for ALP. Mineralization was significantly higher for cells seeded on TiO2 than on Ti granules or pure cells. Expression of ALPL and RUNX2 was significantly higher for cells seeded on TiO2 granules and expression of COL1α1 for pure cells was significantly higher than for cells seeded on granules. Conclusion: ADMSCs have osteogenic potential. Mineralization was significantly high when cells were seeded on TiO2 granules. TiO2 granules may be used as carriers for adipose derived mesenchymal osteoblastic cells from laboratory bench to the patient. [Copyright &y& Elsevier]

Abstract: Background: We determined the predictive power of tobacco smoking on aortic aneurysm as opposed to other risk factors in the general population. Methods: We recorded tobacco smoking and other risk factors at baseline, and assessed hospitalization and death from aortic aneurysm in 15,072 individuals from the Copenhagen City Heart Study followed for up to 34years and in 56,211 individuals from the Copenhagen General Population Study followed for up to 7years. Results: During follow-up, 335 and 169 individuals developed aortic aneurysm outcomes in the Copenhagen City Heart Study and Copenhagen General Population Study, respectively. According to the magnitude of the hazard ratios, tobacco consumption was the most important risk factor for hospitalization and death from aortic aneurysm, followed by male sex and hypertension in both cohorts. The population attributable risk of aortic aneurysm outcomes due to tobacco consumption was 64% and 47% in the Copenhagen City Heart Study and Copenhagen General Population Study, respectively, and ranked highest among population attributable risks of aortic aneurysm in both cohorts. The absolute 10-year risk for hospitalization or death from aortic aneurysm in males and females consuming above 20g tobacco daily was 3.5% and 1.3%, among those >60years with plasma cholesterol >5mmol/L and a systolic blood pressure >140mmHg. Conclusions: Tobacco smoking is the most important predictor of future aortic aneurysm outcomes in the general population, with population attributable risks at or above 47%. [Copyright &y& Elsevier]