Hyperpolarized [1,4‐13C]‐diethylsuccinate: a potential DNP substrate for in vivo metabolic imaging

The tricarboxylic acid (TCA) cycle performs an essential role in the regulation of energy and metabolism, and deficiencies in this pathway are commonly correlated with various diseases. However, the development of non‐invasive techniques for the assessment of the cycle in vivo has remained challenging. In this work, the applicability of a novel imaging agent, [1,4‐¹³C]‐diethylsuccinate, for hyperpolarized ¹³C metabolic imaging of the TCA cycle was explored. In vivo spectroscopic studies were conducted in conjunction with in vitro analyses to determine the metabolic fate of the imaging agent. Contrary to previous reports (Zacharias NM et al. J. Am. Chem. Soc. 2012; 134: 934–943), [¹³C]‐labeled diethylsuccinate was primarily metabolized to succinate‐derived products not originating from TCA cycle metabolism. These results illustrate potential issues of utilizing dialkyl ester analogs of TCA cycle intermediates as molecular probes for hyperpolarized ¹³C metabolic imaging. Copyright © 2014 John Wiley & Sons, Ltd.     

Prevalence of low LDL-cholesterol levels and elevated high-sensitivity C-reactive protein levels in apparently healthy Korean adults

Background and aimsThe Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin (JUPITER) reported reduced cardiovascular and all-cause mortality in patients with elevated C-reactive protein (CRP) and low LDL-cholesterol (LDL-C) levels treated with statins. The aims of this study were to determine the proportion of “JUPITER-eligible” Korean adults and to describe their characteristics.Methods and resultsAs many as 15,154 subjects with serum LDL-C levels <130 mg/dL were selected among 28,851 middle-aged participants (men ≥ 50 years, women ≥ 60 years) who participated in a routine health check-up program. Among the participants with LDL-C less than 130 mg/dL, only 15% had CRP levels ≥2.0 mg/L (7.9% of original participants). Subjects were divided into four groups according to CRP levels (<0.5, ≥0.5 ? <1.0, ≥1.0 ? <2.0, and ≥2.0 mg/L). Mean HDL-C and apolipoprotein A1 levels decreased significantly as the mean CRP values increased. The insulin and homeostasis model of insulin resistance was significantly different according to CRP quartile. The number of subjects with metabolic syndrome and its components increased significantly as the mean CRP values increased.ConclusionIn this Asian population, few individuals with low LDL-C levels had CRP levels ≥2.0 mg/L. Elevated CRP levels were associated with components of atherogenic dyslipidemia and insulin resistance. Additional clinical trials should be designed and performed in different ethnic groups, as different CRP cut-off levels may be required in different ethnic groups.     

Augmentation of natural cytotoxicity by chronic low-dose ionizing radiation in murine natural killer cells primed by IL-2

The possible beneficial effects of chronic low-dose irradiation (LDR) and its mechanism of action in a variety of pathophysiological processes such as cancer are a subject of intense investigation. While animal studies involving long-term exposure to LDR have yielded encouraging results, the influence of LDR at the cellular level has been less well defined. We reasoned that since natural killer (NK) cells constitute an early responder to exogenous stress, NK cells may reveal sentinel alterations in function upon exposure to LDR. When purified NK cells received LDR at 4.2 mGy/h for a total of 0.2 Gy in vitro, no significant difference in cell viability was observed. Likewise, no functional changes were detected in LDR-exposed NK cells, demonstrating that LDR alone was insufficient to generate changes at the cellular level. Nonetheless, significant augmentation of cytotoxic, but not proliferative, function was detected when NK cells were stimulated with low-dose IL-2 prior to irradiation. This enhancement of NK cytotoxicity was not due to alterations in NK-activating receptors, NK1.1, NKG2D, CD69 and 2B4, or changes in the rate of early or late apoptosis. Therefore, LDR, in the presence of suboptimal cytokine levels, can facilitate anti-tumor cytotoxicity of NK cells without influencing cellular proliferation or apoptosis. Whether these results translate to in vivo consequences remains to be seen; however, our data provide initial evidence that exposure to LDR can lead to subtle immune-enhancing effects on NK cells and may explain, in part, the functional basis underlying, diverse beneficial effects seen in the animals chronically exposed to LDR.