Platelet‐rich plasma protects rotator cuff‐derived cells from the deleterious effects of triamcinolone acetonide

Triamcinolone acetonide (TA) injections are widely used to treat enthesopathy, but they may induce adverse effects such as tendon impairment and rupture. Platelet‐rich plasma (PRP) is a blood fraction containing high platelet concentrations and various growth factors that play a role in tissue repair processes. The purpose of this study is to investigate whether TA has deleterious effects on human rotator cuff‐derived cells, and if PRP can protect these cells from the effects of TA. Human rotator cuff‐derived cells were cultured with and without TA and PRP, and the culture without any additive served as the control. Cell morphology was assessed at days 7 and 21. Cell viability was evaluated at days 1, 7, 14, and 21 by a water‐soluble tetrazolium salt assay. Induction of apoptosis was measured by immunofluorescence staining and flow cytometry at day 7. Induction of cleaved caspase‐3 was measured by immunofluorescence staining at day 7. The cells cultured with TA had a flattened and polygonal shape at day 7. The cells cultured with both TA and PRP were similar in appearance to control cells. Exposure to TA also significantly decreased cell viability, but cell viability did not decrease when PRP was added along with TA. The number of apoptotic cells increased with TA exposure, while addition of PRP prevented cell apoptosis. In conclusion, the deleterious effect of TA was prevented by PRP, which can be used as a protective agent for patients receiving local TA injections. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31: 976–982, 2013     

Cell membrane-derived lysophosphatidylcholine activates cardiac ryanodine receptor channels

Lysophosphatidylcholine (LPC) is metabolized from a membrane phospholipid and modulates a variety of channels in the plasma membrane (PM). We examined LPC modulation of cardiac ryanodine receptor (RyR) channels in the sarcoplasmic reticulum (SR) using the planar lipid bilayer method to measure the single-channel currents. Micromolar concentrations of LPC increased the open probability of the reconstituted RyR channels irrespective of whether LPC was added to the cis or trans chamber. LPC also increased the membrane capacitance of the bilayer. The effects of LPC contrasted well with those of sphingosylphosphorylcholine (SPC). Taken together, these results suggest that amphipathic lipid LPC does not bind directly to the RyR channel protein, but rather, is incorporated into the bilayer membrane and activates the channel. Thus, we consider cell membrane-derived LPC to be a putative endogenous mediator that activates not only plasma membrane channels but also RyR channels and induces arrhythmogenic Ca²⁺ mobilization in cardiomyocytes.     

Acquisition of antimicrobial-resistant variants in repeated infections caused by Pseudomonas aeruginosa revealed by whole genome sequencing

Pseudomonas aeruginosa, responsible for serious nosocomial-acquired infections, possesses intrinsic antibiotic resistance mechanisms and commonly exhibits multidrug resistance. Here, we report the evolving resistance profiles of strains isolated from the sputum of a patient being treated for repeated P. aeruginosa infections following cancer resection. Whole genome sequencing of six isolates obtained over a 2-month period revealed two key single nucleotide polymorphisms in the mexR and gyrB genes that affected efflux pump expression and antimicrobial resistance.     

Usefulness of subclassification of adult diabetes mellitus among inpatients in Japan

Aims/IntroductionWe aimed to replicate a new diabetes subclassification based on objective clinical information at admission in a diabetes educational inpatient program. We also assessed the educational outcomes for each cluster.MethodsWe included diabetes patients who participated in the educational inpatient program during 2009–2020 and had sufficient clinical information for the cluster analysis. We applied a data‐driven clustering method proposed in a previous study and further evaluated the clinical characteristics of each cluster. We investigated the association between the clusters and changes in hemoglobin A1c level from the start of the education program. We also assessed the risk of re‐admission for the educational program.ResultsWe divided a total of 651 patients into five clusters. Their clinical characteristics followed the same pattern as in previous studies. The intercluster ranking of the cluster center coordinates showed strong correlation coefficients with those of the previous studies (mean ρ = 0.88). Patients classified as severe insulin‐resistant diabetes (cluster 3) showed a more pronounced progression of renal dysfunction than patients classified as the other clusters. The patients classified as severe insulin‐deficient diabetes (cluster 2) had the highest rate of reduction in hemoglobin A1c level from the start of the program (P < 0.01) and a tendency toward a lower risk of re‐admission for the education program (hazard ratio 0.47, P = 0.09).ConclusionWe successfully replicated the diabetes subclassification using objective clinical information at admission for the education program. In addition, we showed that severe insulin‐deficient diabetes patients tended to have better educational outcomes than patients classified as the other clusters.