Inhibiting activin‐A signaling stimulates bone formation and prevents cancer‐induced bone destruction in vivo

Cancers that grow in bone, such as myeloma and breast cancer metastases, cause devastating osteolytic bone destruction. These cancers hijack bone remodeling by stimulating osteoclastic bone resorption and suppressing bone formation. Currently, treatment is targeted primarily at blocking bone resorption, but this approach has achieved only limited success. Stimulating osteoblastic bone formation to promote repair is a novel alternative approach. We show that a soluble activin receptor type IIA fusion protein (ActRIIA.muFc) stimulates osteoblastogenesis (p < .01), promotes bone formation (p < .01) and increases bone mass in vivo (p < .001). We show that the development of osteolytic bone lesions in mice bearing murine myeloma cells is caused by both increased resorption (p < .05) and suppression of bone formation (p < .01). ActRIIA.muFc treatment stimulates osteoblastogenesis (p < .01), prevents myeloma‐induced suppression of bone formation (p < .05), blocks the development of osteolytic bone lesions (p < .05), and increases survival (p < .05). We also show, in a murine model of breast cancer bone metastasis, that ActRIIA.muFc again prevents bone destruction (p < .001) and inhibits bone metastases (p < .05). These findings show that stimulating osteoblastic bone formation with ActRIIA.muFc blocks the formation of osteolytic bone lesions and bone metastases in models of myeloma and breast cancer and paves the way for new approaches to treating this debilitating aspect of cancer. © 2010 American Society for Bone and Mineral Research.     

Genetic contributions to left ventricular hypertrophy

Left ventricular (LV) hypertrophy is a common condition that profoundly affects morbidity and mortality from cardiovascular diseases, including myocardial infarction, congestive heart failure, and stroke. Noninvasive imaging methods have greatly expanded our ability to evaluate cardiac structural and functional characteristics, and enhanced our understanding of the natural history of L hypertrophy. The etiology of LV hypertrophy is likely due to the effects of multiple genes interacting with other genes and the environment. Although hypertension is recognized as a strong determinant of LV hypertrophy, blood pressure explains only a limited amount of the interindividual variation in LV mass. Moreover, LV hypertrophy occurs in the absence of hypertension, and in some cases precedes its development. Genes encoding proteins involved in the structure of the LV, as well as genes encoding cell signal transduction, hormones, growth factors, calcium homeostasis, and blood pressure, are likely candidates for the development of common forms of LV hypertrophy. An overview of the epidemiology and pathophysiology of LV hypertrophy and dysfunction is provided, in addition to evidence of the genetic basis for LV hypertrophy.     

Anaesthesia for paediatric cardiac MRI

Background: General anaesthesia (GA) for cardiac magnetic resonance imaging (MRI) in patients with congenital heart disease (CHD) is challenging for the anaesthesiologist.     

Muscular sufficiency, serum protein, enzymes and bioenergetic studies (31-phosphorus magnetic resonance spectroscopy) in chronic malnutrition

Muscle sufficiency was significantly lower in 1336 children with chronic malnutrition of moderate to severe degree. Eighteen children with a chronic moderate degree of malnutrition and 8 well-nourished, age-matched controls were selected for biochemical and 31-phosphorus magnetic resonance spectroscopy (31 -P MRS) studies. The results showed that: (a) serum total protein, albumin, iron, calcium and inorganic phosphate were similar in both groups; (b) serum enzyme levels were significantly increased in the malnourished group; (c) 31-P MRS showed significantly higher means for total ATP, β-ATP, a-ATP and inorganic phosphate for the malnourished compared to the control group. In chronic malnutrition, proteins are maintained by degradation in muscle resulting in release of amino acids and enzymes. 31-P MRS studies showing increases in total ATP, β-ATP and inorganic phosphate and a decrease in phosphocreatine suggest that ATP is maintained at the cost of phosphocreatine.     

高效液相色谱法测定血浆中洛美沙星浓度及其在人体内药代动力学

建立了人血浆洛美沙星的反相离子对高效液相色谱测定方法。该法简便易行,精密度好,方法回收率95～102%,日内、日间RSD为2.1～7.8%,血药浓度在0.125～5.012 μg/ml范围内呈线性关系,相关系数0.9998,当S/N=2时,最小检测浓度为25 ng/ml。健康志愿者口服400 mg洛美沙星,药代动力学过程符合一室模型,消除相半衰期为5.5 h。