Modeling statin myopathy in a human skeletal muscle microphysiological system.

Statins are used to lower cholesterol and prevent cardiovascular disease. Musculoskeletal side effects known as statin associated musculoskeletal symptoms (SAMS), are reported in up to 10% of statin users, necessitating statin therapy interruption and increasing cardiovascular disease risk. We tested the hypothesis that, when exposed to statins ex vivo, engineered human skeletal myobundles derived from individuals with (n = 10) or without (n = 14) SAMS and elevated creatine-kinase levels exhibit statin-dependent muscle defects.

Endothelial Contributions to Zebrafish Heart Regeneration.

Studies over the past two decades have shown heart regeneration in zebrafish to be a dynamic process, choreographed by multiple cell types. In particular, recent work has identified revascularization of the wound to be a sentinel event during heart regeneration. The cardiac endothelium has emerged as a key orchestrator of heart regeneration, influencing cardiomyocyte hyperplasia and tissue morphogenesis.

A system to monitor statin-induced myopathy in individual engineered skeletal muscle myobundles.

Microphysiological tissue engineering models of human skeletal muscle (myobundles) provide a platform to investigate the mechanism of muscle diseases and to study the response to drugs and toxins in vitro. To examine the dynamic response to drugs, which often take several days to induce responses, we developed a system to monitor the contractile force of the same human skeletal muscle myobundles over time before and after treatment with drugs. Myobundles were formed in series with Ecoflex films (platinum-catalyzed silicones) with embedded microbeads.

Tissue-engineered blood vessels as promising tools for testing drug toxicity.

Drug-induced vascular injury (DIVI) is a serious problem in preclinical studies of vasoactive molecules and for survivors of pediatric cancers. DIVI is often observed in rodents and some larger animals, primarily with drugs affecting vascular tone, but not in humans; however, DIVI observed in animal studies often precludes a drug candidate from continuing along the development pipeline. Thus, there is great interest by the pharmaceutical industry to identify quantifiable human biomarkers of DIVI.

Biological and engineering design considerations for vascular tissue engineered blood vessels (TEBVs).

Considerable advances have occurred in the development of tissue-engineered blood vessels (TEBVs) to repair or replace injured blood vessels, or as systems for drug toxicity testing. Here we summarize approaches to produce TEBVs and review current efforts to (1) identify suitable cell sources for the endothelium and vascular smooth muscle cells, (2) design the scaffold to mimic the arterial mechanical properties and (3) regulate the functional state of the cells of the vessel wall. Initial clinical studies have established the feasibility of this approach and challenges that make TEBVs a viable alternative for vessel replacement are identified.

Late-outgrowth endothelial progenitors from patients with coronary artery disease: endothelialization of confluent stromal cell layers.

Patients with coronary artery disease (CAD) are the primary candidates to receive small-diameter tissue-engineered blood vessels (TEBVs). Peripheral blood derived endothelial progenitor cells (EPCs) from CAD patients (CAD EPCs) represent a minimally invasive source of autologous cells for TEBV endothelialization. We have previously shown that human CAD EPCs are highly proliferative and express many of the hallmarks of mature and healthy endothelial cells; however, their behavior on stromal cells that comprise the media of TEBVs has not yet been evaluated.

Laboratory evaluation of alternative control methods against the false tiger, Monosteira unicostata (Hemiptera: Tingidae).

Background: Monosteira unicostata is an important pest of almond tree in the Mediterranean region requiring control methods alternative to synthetic pesticides. The efficacy of kaolin, azadirachtin and potassium salts of fatty acids combined with thyme essential oil against adults and fourth instar nymphs of this tingid was evaluated in laboratory assays.

Results: In no choice assays with adults, kaolin significantly increased mortality compared to control (42.

Laboratory tests of insect growth regulators as bait sprays for the control of the olive fruit fly, Bactrocera oleae (Diptera: Tephritidae).

Background: Insect growth regulators (IGRs) act specifically on arthropods. This selectivity makes them an interesting alternative to traditional insecticides for pest control. The aim of this work was to test the IGRs azadirachtin, cyromazine, flufenoxuron, lufenuron and pyriproxyfen as useful pesticides for the control of the olive fruit fly, Bactrocera oleae (Rossi), a key pest of olive crops.