Safety and feasibility of percutaneous autologous skeletal myoblast transplantation in the coil-infarcted swine myocardium

INTRODUCTION: Autologous skeletal myoblast transplantation (ASMT) for myocardial regeneration is a promising new treatment for patients with congestive heart failure secondary to myocardial infarction (MI). However, non-surgical delivery could broaden the utility of this approach. The present study was designed to evaluate the safety and feasibility of transplanting autologous skeletal myoblast (ASM) via endovascular delivery into the infarcted swine myocardium. METHODS: Seven female Yorkshire swine successfully underwent induced left ventricular MI. ASM biopsies were obtained from the hind limb of each animal and myoblasts were expanded in vitro. In a pilot experiment, ASM were labeled with iridium and short-term retention and biodistribution was determined 2 h after ASM delivery via the MyoStar needle-injection catheter inserted through the femoral artery. At 30 days post-infarction, the remaining animals were divided into three groups containing 2 animals each for percutaneous catheter delivery into the infarcted zone: group 1 control animals were injected with media only, group 2 and 3 animals were injected with approximately 300 x 10(6) and 600 x 10(6) ASM, respectively. Sixty days post-transplantation, the swine hearts were harvested. RESULTS: During the 60-day period between transplantation and harvest, no adverse events were recorded, and continuous rhythm monitoring revealed no arrhythmias. In the small sampling size, myocardial function assessments revealed a trend toward improvement in the treatment groups with respect to ejection fraction, viability, and cardiac index. However, histology of treated swine hearts identified no skeletal muscle cells. DISCUSSION: Percutaneous ASMT into an infarcted swine myocardium is feasible and safe, and may contribute to overall improved heart function.     

The potential impact of structural genomics on tuberculosis drug discovery

Mycobacterium tuberculosis, the causative agent of tuberculosis (TB) in humans, is a devastating infectious organism that kills approximately two million people annually. The current suite of antibiotics used to treat TB faces two main difficulties: (i) the emergence of multidrug-resistant (MDR) strains of M. tuberculosis, and (ii) the persistent state of the bacterium, which is less susceptible to antibiotics and causes very long antibiotic treatment regimes. The complete genome sequences of a laboratory strain (H37Rv) and a clinical strain (CDC1551) of M. tuberculosis and the concurrent identification of all the open reading frames that encode proteins within this organism, present structural biologists with a wide array of protein targets for structure determination. Comparative genomics of the species that make up the M. tuberculosis complex has also added an array of genomic information to our understanding of these organisms. In response to this, structural genomics consortia have been established for targeting proteins from M. tuberculosis. This review looks at the progress of these major initiatives and the potential impact of large scale structure determination efforts on the development of inhibitors to many proteins. Increasing sophistication in structure-based drug design approaches, in combination with increasing numbers of protein structures and inhibitors for TB proteins, will have a significant impact on the downstream development of TB antibiotics.     

PROPERDIN FACTOR D: CHARACTERIZATION OF ITS ACTIVE SITE AND ISOLATION OF THE PRECURSOR FORM

The activity of properdin factor D was measured by the generation of the hemolytically active cellular intermediate, EAC43B(D), bearing the C3b-dependent alternate pathway C3 convertase. Treatment of factor D with DFP prevented formation of EAC43B(D); thus, a serine esterase is essential for the generation of the alternate pathway C3 convertase, a situation analogous to the role of C1 in the formation of the classical C3 convertase, C42. The definition of factor D as a serine esterase prompted a search for its proenzyme form, and resulted in the chromatographic isolation from plasma of a single peak of trypsin-inducible factor D activity, distinct from activated factor D. Analytical gel filtration indicated an apparent mol wt of 25,000. This protein from which trypsin elaborated factor D activity, as assessed by the formation of EAC43B(D), the generation of the CoVF-dependent C3 convertase, and the cleavage of factor B in the presence of C3b, was designated "precursor factor D." The DFP resistance of precursor factor D, and the susceptibility of its trypsin-activated form to inactivation by DFP is analogous to the behavior of other plasma serine esterases, including C1.     

Do dorsal head contact forces have the potential to identify impairment during graded craniocervical flexor muscle contractions?

OBJECTIVE: To determine if the force exerted onto the supporting surface by the dorsal head during graded contractions of isometric craniocervical flexion (ICCF) in the supine position has the potential to measure aberrant muscle performance between participant groups with and without painful neck disorders. DESIGN: Cross-sectional, between-participant study of the force exerted by the head on the supporting surface during ICCF muscle contractions. SETTING: Research laboratory. PARTICIPANTS: Thirty-two participants with a history of neck pain and 32 asymptomatic control participants. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Dorsal head force (DHF), which is the force (in newtons) exerted by the head on the supporting surface during ICCF muscle contractions in the supine position. ICCF muscle contractions were performed at maximal voluntary contraction (MVC), and sustained at contractions of 50% of MVC and 20% of MVC. RESULTS: Both neck pain and control participants significantly increased their DHF on the supporting surface from resting values during all ICCF muscle contractions (P<.001). No differences in DHF were found between symptomatic and control participants during any of the ICCF efforts. CONCLUSIONS: It would appear that DHF exerted on the supporting surface during graded ICCF muscle contractions is similar between neck pain sufferers and control participants, and is therefore limited in its usefulness as a measurement of abnormal performance.