Nonalcoholic fatty liver disease (NAFLD) is the most common type of chronic liver disease worldwide and includes a broad spectrum of histologic phenotypes, ranging from simple hepatic steatosis or nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). While liver biopsy is the reference gold standard for NAFLD diagnosis and staging, it has limitations due to its sampling variability, invasive nature, and high cost. Thus, there is a need for noninvasive biomarkers that are robust, reliable, and cost effective. In this study, we measured 540 lipids and amino acids in serum samples from biopsy‐proven subjects with normal liver (NL), NAFL, and NASH. Using logistic regression analysis, we identified two panels of triglycerides that could first discriminate between NAFLD and NL and second between NASH and NAFL. These noninvasive tests were compared to blinded histology as a reference standard. We performed these tests in an original cohort of 467 patients with NAFLD (90 NL, 246 NAFL, and 131 NASH) that was subsequently validated in a separate cohort of 192 patients (7 NL, 109 NAFL, 76 NASH). The diagnostic performances of the validated tests showed an area under the receiver operating characteristic curve, sensitivity, and specificity of 0.88 ± 0.05, 0.94, and 0.57, respectively, for the discrimination between NAFLD and NL and 0.79 ± 0.04, 0.70, and 0.81, respectively, for the discrimination between NASH and NAFL. When the analysis was performed excluding patients with glucose levels >136 mg/dL, the area under the receiver operating characteristic curve for the discrimination between NASH and NAFL increased to 0.81 ± 0.04 with sensitivity and specificity of 0.73 and 0.80, respectively. Conclusion: The assessed noninvasive lipidomic serum tests distinguish between NAFLD and NL and between NASH and NAFL with high accuracy. (Hepatology Communications 2018;2:807‐820)

SUMMARY1. Adult rabbit carotid body chemoreceptor cells, enzymatically dispersed and short-term cultured, exhibit an inactivating outward K+ current that is reversibly inhibited by low PO . In the present work we have characterized the biophysical and pharmacological properties of this current using the whole-cell voltage clamp recording technique.2. Inactivating current was recorded after blockage of Ca2+ currents with extracellular Co2+, Cd2+, or after complete washing out of Ca2+ channels.3. The threshold of activation of this inactivating current was about -40 mV. Current activated very quickly (mean rise time 4-8 + 0-42 ms at + 60 mV) but inactivated more slowly. Inactivation was well fitted by two exponentials with time constants of 79-7 + 6-6 and 824 + 42-8 ms (at + 40 mV). The inactivation process showed a little voltage dependence.4. The steady-state inactivation was well fitted by a Boltzman function. Inactivation was fully removed at potentials negative to -80 mV and was complete at voltages near -10 mV; 50 % inactivation occurred at -41 mV.5. Recovery from inactivation had several components and was voltage dependent. Initial recovery was fast, but full recovery, even at -100 mV, required more than 30 s. 6. Inactivating current was selectively blocked by 4-aminopyridine (4-AP), in a dose-dependent manner (IC50, 0-2 mM). The duration of chemoreceptor cells action potentials was augmented by 1 mm 4-AP from 2-3 + 0-36 to 7-0 ± 0+25 ms at 0 mV. Tetraethylamonium (TEA), at concentrations above 5 mm, blocked inactivating and non-inactivating components of the whole K+ current.7. Inactivating current was modulated by cyclic AMP (cAMP). Bath application of 2 mm dibutyryl cAMP reduced peak amplitude by 18-7 + 2-9 % (at + 30 mV) and slowed down the rise time of the current. The effect was not voltage dependent. Forskolin (10-20 /LM) also affected inactivating current, by accelerating the inactivation process. In the same preparations neither dibutyryl cAMP nor forskolin affected Ca21 currents.8. It is concluded that modulation of K+ channels by cAMP might play a physiological role potentiating the low Po2 inhibition of K+ channels.

,5-triaza-7-phosphaadamantane-7-oxide (PTA=O) and DION, respectively. All complexes are water soluble and have been characterized by IR, far-IR, H-1, C-13 and P-31{H-1} NMR spectroscopy, ESI-MS, elemental analyses and single-crystal X-ray diffraction structural analysis (for 1). They were screened against the human tumour cell lines HCT116, HepG2 and MCF7. Complexes 2 and 3 exhibit the highest in vitro cytotoxicity and show lower cytotoxic activities in normal human fibroblast cell line than in HCT116 tumour cell line, which demonstrates their slight specificity for this type of tumour cell.

No abstract