Blood Flow Restriction Therapy Versus Standard Care for Reducing Quadriceps Atrophy After Anterior Cruciate Ligament Reconstruction.

Clinical Scenario: Quadriceps atrophy and weakness are common after anterior cruciate ligament reconstruction (ACLR). Blood flow restriction (BFR) therapy, alone or in combination with exercise, has shown some promise in promoting muscular hypertrophy. This review was conducted to ascertain the extent to which current evidence supports the use of BFR for reducing quadriceps atrophy following ACLR in comparison with standard care. Clinical Question: Is BFR more effective than standard care for reducing quadriceps atrophy after ACLR? Summary of Key Findings: The literature was searched for studies that directly compared BFR treatment to standard care in patients with ACLR. Three level I randomized control trial studies retrieved from the literature search met the inclusion criteria. Clinical Bottom Line: Reviewed data suggest that a short duration (13 d) of moderate-pressure BFR combined with low-resistance muscular training does not appear to measurably affect quadriceps cross-sectional area. However, a relatively long duration (15 wk) of moderate-pressure BFR combined with low-resistance muscular training may increase quadriceps cross-sectional area to a greater extent than low-resistance muscular training alone. The results of the third randomized control trial suggest that employing BFR while immobilized in the early postoperative period may reduce quadriceps atrophy following ACLR. Additional data are needed to establish if the benefits of BFR on quadriceps atrophy after ACLR outweigh the inherent risks and costs. Strength of Recommendation: All evidence for this review was level 1 (randomized control trial) based on the Centre for Evidence-Based Medicine criteria. However, the findings were inconsistent across the 3 studies regarding the effects of BFR on quadriceps atrophy resulting in a grade "B" strength of recommendation.

Identification of Staphylococcus aureus Cellular Pathways Affected by the Stilbenoid Lead Drug SK-03-92 Using a Microarray.

The mechanism of action for a new lead stilbene compound coded SK-03-92 with bactericidal activity against methicillin-resistant Staphylococcus aureus (MRSA) is unknown. To gain insight into the killing process, transcriptional profiling was performed on SK-03-92 treated vs. untreated S. aureus. Fourteen genes were upregulated and 38 genes downregulated by SK-03-92 treatment. Genes involved in sortase A production, protein metabolism, and transcriptional regulation were upregulated, whereas genes encoding transporters, purine synthesis proteins, and a putative two-component system (SACOL2360 (MW2284) and SACOL2361 (MW2285)) were downregulated by SK-03-92 treatment. Quantitative real-time polymerase chain reaction analyses validated upregulation of srtA and tdk as well as downregulation of the MW2284/MW2285 and purine biosynthesis genes in the drug-treated population. A quantitative real-time polymerase chain reaction analysis of MW2284 and MW2285 mutants compared to wild-type cells demonstrated that the srtA gene was upregulated by both putative two-component regulatory gene mutants compared to the wild-type strain. Using a transcription profiling technique, we have identified several cellular pathways regulated by SK-03-92 treatment, including a putative two-component system that may regulate srtA and other genes that could be tied to the SK-03-92 mechanism of action, biofilm formation, and drug persisters.

Docking into Mycobacterium tuberculosis Thioredoxin Reductase Protein Yields Pyrazolone Lead Molecules for Methicillin-Resistant Staphylococcus aureus.

The thioredoxin/thioredoxin reductase system (Trx/TrxR) is an attractive drug target because of its involvement in a number of important physiological processes, from DNA synthesis to regulating signal transduction. This study describes the finding of pyrazolone compounds that are active against Staphylococcus aureus. Initially, the project was focused on discovering small molecules that may have antibacterial properties targeting the Mycobacterium tuberculosis thioredoxin reductase. This led to the discovery of a pyrazolone scaffold-containing compound series that showed bactericidal capability against S. aureus strains, including drug-resistant clinical isolates. The findings support continued development of the pyrazolone compounds as potential anti-S. aureus antibiotics.