Lung inflammatory environments differentially alter mesenchymal stromal cell behavior.

Mesenchymal stromal (stem) cells (MSCs) are increasingly demonstrated to ameliorate experimentally induced lung injuries through disease-specific anti-inflammatory actions, thus suggesting that different in vivo inflammatory environments can influence MSC actions. To determine the effects of different representative inflammatory lung conditions, human bone marrow-derived MSCs (hMSCs) were exposed to in vitro culture conditions from bronchoalveolar lavage fluid (BALF) samples obtained from patients with either the acute respiratory distress syndrome (ARDS) or with other lung diseases including acute respiratory exacerbations of cystic fibrosis (CF) (non-ARDS). hMSCs were subsequently assessed for time- and BALF concentration-dependent effects on mRNA expression of selected pro- and anti-inflammatory mediators, and for overall patterns of gene and mRNA expression. Both common and disease-specific patterns were observed in gene expression of different hMSC mediators, notably interleukin (IL)-6. Conditioned media obtained from non-ARDS BALF-exposed hMSCs was more effective in promoting an anti-inflammatory phenotype in monocytes than was conditioned media from ARDS BALF-exposed hMSCs. Neutralizing IL-6 in the conditioned media promoted generation of anti-inflammatory monocyte phenotype. This proof of concept study suggest that different lung inflammatory environments potentially can alter hMSC behaviors. Further identification of these interactions and the driving mechanisms may influence clinical use of MSCs for treating lung diseases.

Heart rate-induced modifications of concentric left ventricular hypertrophy: exploration of a novel therapeutic concept.

Lowering the heart rate is considered to be beneficial in heart failure (HF) with reduced ejection fraction (HFrEF). In a dilated left ventricle (LV), pharmacological heart rate lowering is associated with a reduction in LV chamber size. In patients with HFrEF, this structural change is associated with better survival. HF with preserved ejection fraction (HFpEF) is increasingly prevalent but, so far, without any evidence-based treatment. HFpEF is typically associated with LV concentric remodeling and hypertrophy. The effects of heart rate on this structural phenotype are not known. Analogous with the benefits of a low heart rate on a dilated heart, we hypothesized that increased heart rates could lead to potentially beneficial remodeling of a concentrically hypertrophied LV. This was explored in an established porcine model of concentric LV hypertrophy and fibrosis. Our results suggest that a moderate increase in heart rate can be used to reduce wall thickness, normalize LV chamber volumes, decrease myocardial fibrosis, and improve LV compliance. Our results also indicate that the effects of heart rate can be titrated, are reversible, and do not induce HF. These findings may provide the rationale for a novel therapeutic approach for HFpEF and its antecedent disease substrate.

Relaxation and the Role of Calcium in Isolated Contracting Myocardium From Patients With Hypertensive Heart Disease and Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Relaxation characteristics and Ca2+ homeostasis have not been studied in isolated myocardium from patients with hypertensive heart disease (HHD) and heart failure with preserved ejection fraction (HFpEF). Prolonged myocardial relaxation is believed to play an important role in the pathophysiology of these conditions. In this study, we evaluated relaxation parameters, myocardial calcium (Ca2+), and sodium (Na+) handling, as well as ion transporter expression and tested the effect of Na+-influx inhibitors on relaxation in isolated myocardium from patients with HHD and HFpEF. METHODS AND RESULTS: Relaxation characteristics were studied in myocardial strip preparations under physiological conditions at stimulation rates of 60 and 180 per minute. Intracellular Ca2+ and Na+ were simultaneously assessed using Fura-2 and AsanteNATRIUMGreen-2, whereas elemental analysis was used to measure total myocardial concentrations of Ca, Na, and other elements. Quantitative polymerase chain reaction was used to measure expression levels of key ion transport proteins. The lusitropic effect of Na+-influx inhibitors ranolazine, furosemide, and amiloride was evaluated. Myocardial left ventricular biopsies were obtained from 36 control patients, 29 HHD and 19 HHD+HFpEF. When compared with control patients, half maximal relaxation time (RT50) at 60 per minute was prolonged by 13% in HHD and by 18% in HHD+HFpEF (both P<0.05). Elevated resting Ca2+ levels and a tachycardia-induced increase in diastolic Ca2+ were associated with incomplete relaxation and an increase in diastolic tension in HHD and HHD+HFpEF. Na+ levels were not increased, and expression levels of Ca2+- or Na+-handling proteins were not altered. Na+-influx inhibitors did not improve relaxation or prevent incomplete relaxation at high stimulation rates. CONCLUSIONS: Contraction and relaxation are prolonged in isolated myocardium from patients with HHD and HHD+HFpEF. This leads to incomplete relaxation at higher rates. Elevated calcium levels in HFpEF are neither a result of an impaired Na+ gradient nor expression changes in key ion transporters and regulatory proteins.

Human papillomavirus (HPV) education in middle and high schools of Vermont.

Human papillomavirus (HPV), the most prevalent sexually transmitted disease (STD), continues to pose a significant public health problem especially among the adolescent population. Most precancerous and cancerous cervical changes are associated with HPV, with adolescent women being biologically at highest risk for acquiring HPV. This survey examined the type of information taught to adolescents about HPV, and specific needs for effective HPV education in middle and high schools in Vermont. The survey addressed knowledge level, behavior, attitudes, enabling factors, motivators, and barriers. Data were analyzed by descriptive statistics and supplemented with contingency table analyses. Replies (n = 108) were received from 79 schools, with 60% of responses from nurses and 40% from teachers. In five of eight questions addressing basic knowledge of HPV, less than 60% of respondents gave the correct answer. Most (73%) felt it was important to teach about HPV relative to HIV/AIDS, but spent less classroom time teaching it. Main motivations for teaching about HPV were its importance, and a desire to increase student knowledge and prevention skills. Main barriers perceived were lack of time and materials and curricula, and need for more knowledge about HPV. The most prominent needs indicated included brochures for students, an increase in the educators' knowledge base, and a high school curriculum. Health educators in Vermont schools recognize the importance of teaching adolescents about HPV, but they lack basic knowledge and resources for teaching about HPV.