Mesenchymal stem cells regulate airway contractile tissue remodeling in murine experimental asthma.

BACKGROUND: Mesenchymal stem cells may offer therapeutic potential for asthma due to their immunomodulatory properties and host tolerability, yet prior evidence suggests that bloodborne progenitor cells may participate in airway remodeling. Here, we tested whether mesenchymal stem cells administered as anti-inflammatory therapy may favor airway remodeling and therefore be detrimental. METHODS: Adipose tissue-derived mesenchymal stem cells were retrovirally transduced to express green fluorescent protein and intravenously injected into mice with established experimental asthma induced by repeat intranasal house dust mite extract. Controls were house dust mite-instilled animals receiving intravenous vehicle or phosphate-buffered saline-instilled animals receiving mesenchymal stem cells. Data on lung function, airway inflammation, and remodeling were collected at 72 h after injection or after 2 weeks of additional intranasal challenge. RESULTS: The mesenchymal stem cells homed to the lungs and rapidly downregulated airway inflammation in association with raised T-helper-1 lung cytokines, but such effect declined under sustained allergen challenge despite a persistent presence of mesenchymal stem cells. Conversely, airway hyperresponsiveness and contractile tissue underwent a late reduction regardless of continuous pathogenic stimuli and inflammatory rebound. Tracking of green fluorescent protein did not show mesenchymal stem cell integration or differentiation in airway wall tissues. CONCLUSIONS: Therapeutic mesenchymal stem cell infusion in murine experimental asthma is free of unwanted pro-remodeling effects and ameliorates airway hyper-responsiveness and contractile tissue remodeling. These outcomes support furthering the development of mesenchymal stem cell-based asthma therapies, although caution and solid preclinical data building are warranted.

Increased cholesterol intake in women with gestational diabetes mellitus.

AIM: Cholesterol intake is associated with the risk for type 2 diabetes mellitus, but no previous studies have evaluated its role regarding the risk of gestational diabetes mellitus (GDM). We investigate the relation between cholesterol intake and GDM. METHODS: At screening for GDM, 335 pregnant women were evaluated for dietary intake (including cholesterol) during the previous year (validated food-frequency questionnaire). RESULTS: Forty-one women were diagnosed with GDM and 294 did not meet the GDM criteria. Women with GDM were older (32.8+/-0.7 vs. 30.2+/-0.3 years; P=0.01) and had a higher body mass index (27.3+/-0.7 vs. 24.3+/-0.3 kg/m2; P=0.01) than women without GDM. They also had more frequently a family history of type 2 diabetes mellitus (51.2% vs. 40.0%; P=0.02) and history of previous GDM (14.6% vs. 1.7%; P=0.01), and were evaluated earlier in pregnancy (22.1+/-1.2 vs. 24.9+/-0.5 weeks; P=0.03). There were no significant differences between groups in smoking habit, and alcohol, total energy, protein, carbohydrate, fats and fiber intake. Women with GDM had a higher cholesterol intake than women without GDM (145.3+/-4.5 mg/1000 kcal vs. 134.5+/-1.6 mg/1000 kcal; P=0.03). In a multiple logistic regression model, previous GDM, BMI, age and cholesterol intake (OR=1.88; 95% CI: 1.09-3.23 for each increase of 50 mg/1000 kcal) were independently and positively associated with GDM. CONCLUSION: We conclude that cholesterol intake is independently associated with GDM and that it could be involved in the pathogenesis of GDM.

Effect of inflammation on the proliferation of human gingival epithelial cells in vitro.

The adaptive or pathologic responses of epithelial cells to inflammation are poorly characterized. The purpose of this study was to determine if epithelial cells cultured from clinically healthy and inflamed human gingival tissues express differences in proliferation rate and viability. Briefly, the inflammation status of individual donor sites from 101 patients was visually assessed at the time of periodontal surgery and categorized as either non-to-slightly inflamed, moderately inflamed, or severely inflamed. Discarded gingival tissues were then processed to obtain primary cell cultures, for which proliferation rates were determined by calculating the ratio of mean population doublings to the number of days required for cultures to become confluent. In general, the cells in the minimally inflamed group exhibited characteristics different than cells in the moderately and severely inflamed groups. Specifically, the cells obtained from clinical sites which exhibited no-to-slight inflammation had a significantly higher mean proliferation rate than cells in either the moderate inflammation group or the severe inflammation group. Based on trypan blue exclusion, the cells obtained from clinical sites which exhibited no-to-slight inflammation also were more viable than cells obtained from sites with moderate inflammation or severe inflammation. Microscopic evaluation showed morphological changes associated with increased inflammation. Cell cycle analysis by fluorescent-activated cell sorting (FACS) revealed a directly proportional relationship between the degree of inflammation and apoptosis, and a strong inversely proportional trend between the degree of inflammation and the numbers of cells undergoing mitosis. Taken together, these data suggest that epithelial cell proliferation and viability are inversely associated with the degree of gingival inflammation, once a putative "adaptive threshold" is exceeded. Elucidation of the underlying mechanisms will likely lead to improvements in clinical diagnosis and treatment.

Mass spectrometric 13C/12C determinations to detect high fructose corn syrup in orange juice: collaborative study.

The 13C/12C ratios in orange juice are sufficiently uniform and different from those in high fructose corn syrup (HFCS) so that the addition of HFCS to orange juice can be detected. HFCS averages -9.7% (parts per thousand) delta 13C, orange juice averages -24.5%, and mixtures of HFCS and orange juice possess intermediate values. One pure orange juice and 4 orange juice -HFCS mixtures containing from 25 to 70% orange juice were properly classified by 7 collaborators. Samples with delta 13C values less negative than -22.1%, 4 standard deviations from the mean of pure juices, can, with a high degree of confidence, be classified as adulterated. Samples with values more negative than -22.1% must be considered unadulterated with HFCS, because pure orange juices possess a range of delta 13C values. The 13C/12C mass spectrometric method was adopted official first action for detecting HFCS in orange juice.