Design features of the Avasimibe and Progression of coronary Lesions assessed by intravascular UltraSound (A-PLUS) clinical trial

Background Although statins have been shown to be beneficial in the management of hyperlipidemia and the reduction of cardiovascular morbidity and mortality, rates of major cardiovascular events remain high despite their use. Inhibition of the acyl coenzyme A: cholesterol acyltransferase (ACAT) enzyme in the arterial wall may prevent excess accumulation of cholesteryl esters in macrophages. In addition to ACAT inhibitor monotherapy, combination of a statin with an ACAT inhibitor may be a promising approach to further prevent the progression of atherosclerosis. Methods This report describes the design and methodologic features of a double-blind, randomized, placebo-controlled trial to assess the effect of the ACAT inhibitor avasimibe at 50-, 250-, and 750-mg daily dosages on the progression of coronary atherosclerosis as assessed by intravascular ultrasound (IVUS). All patients receive background lipid-lowering therapy when necessary. The study population consists of patients with at least one 20% to 50% diameter stenosis in a coronary artery with a reference diameter of ≥2.5 mm. IVUS and coronary angiography are performed at baseline and repeated at 24 months. The primary study end point is the change from baseline in plaque volume in a 30-mm segment of the coronary artery assessed by 3-dimensional IVUS. Several other IVUS and angiographic end points are measured. Conclusions The Avasimibe and Progression of coronary Lesions assessed by intravascular UltraSound (A-PLUS) trial is among the first large imaging trials to use IVUS as a primary end point and assesses the effects of the ACAT inhibitor avasimibe on atherosclerosis progression. (Am Heart J 2002;144:589-96.)     

Comparing human and mouse salivary glands: A practice guide for salivary researchers

Mice are a widely utilized in vivo model for translational salivary gland research but must be used with caution. Specifically, mouse salivary glands are similar in many ways to human salivary glands (i.e., in terms of their anatomy, histology, and physiology) and are both readily available and relatively easy and affordable to maintain. However, there are some significant differences between the two organisms, and by extension, the salivary glands derived from them must be taken into account for translational studies. The current review details pertinent similarities and differences between human and mouse salivary glands and offers practical guidelines for using both for research purposes.     

White adipose tissue mitochondrial metabolism in health and in obesity

White adipose tissue is one of the largest organs of the body. It plays a key role in whole‐body energy status and metabolism; it not only stores excess energy but also secretes various hormones and metabolites to regulate body energy balance. Healthy adipose tissue capable of expanding is needed for metabolic well‐being and to prevent accumulation of triglycerides to other organs. Mitochondria govern several important functions in the adipose tissue. We review the derangements of mitochondrial function in white adipose tissue in the obese state. Downregulation of mitochondrial function or biogenesis in the white adipose tissue is a central driver for obesity‐associated metabolic diseases. Mitochondrial functions compromised in obesity include oxidative functions and renewal and enlargement of the adipose tissue through recruitment and differentiation of adipocyte progenitor cells. These changes adversely affect whole‐body metabolic health. Dysfunction of the white adipose tissue mitochondria in obesity has long‐term consequences for the metabolism of adipose tissue and the whole body. Understanding the pathways behind mitochondrial dysfunction may help reveal targets for pharmacological or nutritional interventions that enhance mitochondrial biogenesis or function in adipose tissue.     

Current cell models for bioengineering a salivary gland: a mini‐review of emerging technologies

Oral Diseases (2013) 19 , 236–244 Saliva plays a major role in maintaining oral health. Patients afflicted with a decrease in saliva secretion (symptomatically, xerostomia) exhibit difficulty in chewing and swallowing foods, tooth decay, periodontal disease, and microbial infections. Despite recent improvements in treating xerostomia (e.g., saliva stimulants, saliva substitutes, and gene therapy), there is a need of more scientific advancements that can be clinically applied toward restoration of compromised salivary gland function. Here we provide a summary of the current salivary cell models that have been used to advance restorative treatments via development of an artificial salivary gland. These models represent initial steps toward clinical and translational research, to facilitate creation of clinically safe salivary glands. Further studies in salivary cell lines and primary cells are necessary to improve survival rates, cell differentiation, and secretory function. Additionally, the characterization of salivary progenitor and stem cell markers are necessary. Although these models are not fully characterized, their improvement may lead to the construction of an artificial salivary gland that is in high demand for improving the quality of life of many patients suffering from salivary secretory dysfunction.     

Construct and predictive validity of a self-reported measure of preclinical mobility limitation

OBJECTIVES: To validate self-reported preclinical mobility limitation concept and self-report assessment method against muscle power and walking speed, and to study the predictive validity of preclinical mobility limitation with respect to future risk of manifest mobility limitation. DESIGN: Observational prospective cohort study and cross-sectional analysis. SETTING: Research laboratory and community. PARTICIPANTS: A total of 632 community-living (age range, 75-81 y) women and men took part in the baseline assessments and 302 persons in the semi-annual interviews on mobility limitation over 2 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Walking speed, muscle power, and self-reported preclinical and manifest mobility limitation. Preclinical mobility limitation was defined as self-reported tiredness or modification of task performance without task difficulty. At baseline, 4 subgroups were created according to self-reported preclinical mobility limitation in any of 3 mobility tasks (walking 2 km, walking 0.5 km, climbing up stairs): no limitation, preclinical limitation, and minor and major manifest limitation. RESULTS: At baseline, participants with preclinical mobility limitation showed intermediate levels of walking speed and muscle power, compared with those with no limitation or manifest mobility limitation. Participants reporting baseline preclinical mobility limitation had 3- to 6-fold higher age- and sex-adjusted risk of progressing to major manifest mobility limitation during the 2-year follow-up compared with participants with no limitation at baseline, whereas the risk among those with minor limitation at baseline was 14- to 18-fold higher compared with those with no limitation. CONCLUSIONS: The self-report assessment tool proved to be a valid measure to capture the early signs of disability and may serve as an inexpensive tool for identifying those nondisabled persons at high risk for future disability.     

Tibial and Fibular Mid-Shaft Bone Traits in Young and Older Sprinters and Non-Athletic Men

High impact loading is known to prevent some of the age-related bone loss but its effects on the density distribution of cortical bone are relatively unknown. This study examined the effects of age and habitual sprinting on tibial and fibular mid-shaft bone traits (structural, cortical radial and polar bone mineral density distributions). Data from 67 habitual male sprinters aged 19–39 and 65–84 years, and 60 non-athletic men (referents) aged 21–39 and 65–80 years are reported. Tibial and fibular mid-shaft bone traits (strength strain index SSI, cortical density CoD, and polar and radial cortical density distributions) were assessed with peripheral quantitative computed tomography. Analysis of covariance (ANCOVA) adjusted for height and body mass indicated that the sprinters had 21 % greater tibial SSI (P < 0.001) compared to the referents, with no group × age-group interaction (P = 0.54). At the fibula no group difference or group × age-group interaction was identified (P = 0.12–0.81). For tibial radial density distribution ANCOVA indicated no group × radial division (P = 0.50) or group × age-group × division interaction (P = 0.63), whereas an age × radial division interaction was observed (P < 0.001). For polar density distribution, no age-group × polar sector (P = 0.21), group × polar sector (P = 0.46), or group × age-group × polar sector interactions were detected (P = 0.15). Habitual sprint training appears to maintain tibial bone strength, but not radial cortical density distribution into older age. Fibular bone strength appeared unaffected by habitual sprinting.     

Asynchronous globin chain synthesis in rabbit reticulocyte lystates induced by hemin-controlled repressor

To define further the role of hemin-controlled repressor (HCR) in globin synthesis, we studied its effect on the synthesis of individual globin chains in a rabbit reticulocyte lysate cell-free system. In the presence of HCR there was a marked globin chain imbalance, resulting in a lowered alpha/beta ratio. These findings in vitro may have relevance to certain clinical heme deficiency states in which a similar globin chain imbalance has been observed.