Novel cardiovascular magnetic resonance oxygenation approaches in understanding pathophysiology of cardiac diseases

Cardiovascular magnetic resonance imaging (CMR) permits accurate phenotyping of many cardiac diseases. CMR’s inherent advantages are its non‐invasive nature, lack of ionizing radiation and high accuracy and reproducibility. Furthermore, it is able to assess many aspects of cardiac anatomy, structure and function. Specifically, it can characterize myocardial tissue, myocardial function, myocardial mass, myocardial blood flow/perfusion, irreversible and reversible injury, all with a high degree of accuracy and reproducibility. Hence, CMR is a powerful tool in clinical and pre‐clinical research. In recent years there have been novel advances in CMR myocardial tissue characterization. Oxygenation‐sensitive CMR (OS‐CMR) is a novel non‐invasive, contrast independent technique that permits direct quantification of myocardial tissue oxygenation, both at rest and during stress. In this review, we will address the principles of the OS‐CMR technique, its recent advances and summarize the studies in the effects of oxygenation on cardiac diseases.     

RhPDCD5 combined with dexamethasone increases antitumor activity in multiple myeloma partially via inhibiting the Wnt signalling pathway

Multiple myeloma (MM) is one of the most common hematological malignancies and characterized by the clonal accumulation of malignant plasma cells. Significant progress has been made in MM treatment recently, while MM still remains incurable. Our previous studies showed that the recombined human programmed cell death 5 (rhPDCD5) can promote MM apoptosis induced by dexamethasone (Dex). Here, we expanded the findings by showing that the rhPDCD5 alone could not induce an obvious growth inhibition of U266 cells (a MM cell line). Of note, with the combination of dexamethasone (Dex), the growth of MM cells was significantly inhibited and accompanied with the cell cycle arrest in G0/G1. For mechanism study, we found that the combination treatment of rhPDCD5 plus Dex downregulated the mRNA and protein expressions of Wnt effectors including β‐catenin, β‐catenin (Ser675), TCF4, survivin and c‐Myc when compared to Dex only. Moreover, the activation of WNT pathway induced by LiCl can also be inhibited by this combination treatment. Taken together, our study demonstrated that the combination of rhPDCD5 and Dex can suppress the proliferation of multiple myeloma cells partially via inhibiting the WNT signalling pathway.     

Radioiodination and bioevaluation of rolipram as a tracer for brain imaging: In silico study,molecular modeling and gamma scintigraphy

Brain imaging is considered one of the most fruitful applications of radioisotope scanning. Rolipram, a selective phospodiesterase‐4 inhibitor, has been labeled using [¹²⁵I] with chloramine‐T (Ch‐T) as an oxidizing agent. Factors, such as the amount of substrate, pH, the amount of oxidizing agent, temperature, and the reaction time, have been systematically studied to optimize the iodination process. In addition, bio‐distribution studies have indicated that the brain uptake of [¹²⁵I]iodorolipram is 7.6 ± 0.33 injected dose/g organ at 10 minutes post‐injection, which cleared from the brain with time until it reaches 1.30 ± 0.17% at 1 hour post‐injection. Therefore, iodorolipram could be considered as a potential, new selective radiotracer for brain imaging.     

Empirical treatment of lower urinary tract infections in the face of spreading multidrug resistance: in vitro study on the effectiveness of nitroxoline

The spread of antimicrobial resistance challenges the empirical treatment of urinary tract infections (UTIs). Among others, nitrofurantoin is recommended for first-line treatment, but acceptance among clinicians is limited due to chronic nitrofurantoin-induced lung toxicity and insufficient coverage of Enterobacteriaceae other than Escherichia coli. Nitroxoline appears to be an alternative to nitrofurantoin owing to its favourable safety profile, however data on its current in vitro susceptibility are sparse. In this study, susceptibility to nitroxoline was tested against 3012 urinary clinical isolates (including multidrug-resistant bacteria and Candida spp.) by disk diffusion test and/or broth microdilution. At least 91% of all Gram-negatives (n?=?2000), Gram-positives (n?=?403) and yeasts (n?=?132) had inhibition zone diameters for nitroxoline ≥18?mm. Except for Pseudomonas aeruginosa, nitroxoline MIC₉₀ values were ≤16?mg/L and were 2- to >16-fold lower compared with nitrofurantoin. In extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae and methicillin-resistant Staphylococcus aureus (MRSA), MIC₉₀ values of nitroxoline were two-fold higher compared with non-ESBL-producing enterobacteria and methicillin-susceptible S. aureus (MSSA). The in vitro efficacies of nitroxoline and nitrofurantoin against ATCC strains of E. coli, Enterococcus faecalis and Proteus mirabilis were compared by time–kill curves in Mueller–Hinton broth and artificial urine. Nitroxoline was non-inferior against E. coli, P. mirabilis and E. faecalis in artificial urine. In conclusion, nitroxoline showed a broad antimicrobial spectrum, with inhibition zone diameters and MICs of nitroxoline well below the EUCAST breakpoint for E. coli for most organisms, and thus may also be a target for therapy of uncomplicated UTIs.