The isotopic composition of blood serum Cu has been investigated as a potential parameter for the diagnosis and prognosis of liver cirrhosis. Serum samples from supposedly healthy women (reference population) and from a group of female patients suffering from liver cirrhosis of different etiologies were analysed. The procedure for isolation of serum Cu and the measurement protocol for its isotopic analysis by multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) were evaluated. Significant differences in the isotopic composition of Cu were observed between the reference population and the patients. A wide spread in δ(65)Cu was observed within the cirrhosis population and δ(65)Cu seems to be linked to the severity of the disease. Patients with end-stage liver disease showed a significantly lighter serum Cu isotopic composition. Many clinical parameters used for the diagnosis and monitoring of liver diseases, i.e. the levels of aspartate aminotransferase, De Ritis ratio, prothrombin and international normalized ratio, albumin, bilirubin, Na and C-reactive protein, correlate well with the δ(65)Cu values, as did the ceruloplasmin level and the ceruloplasmin/Cu concentration ratio. The isotopic composition of serum Cu appears to reveal the synthetic and hepatocellular function of the liver synergistically with inflammation and fluid retention in the cohort studied. A relevant relationship was also observed between δ(65)Cu and scores of mortality risk, such as the Model for End-stage Liver Disease (MELD) and MELD-Na. Thus, the isotopic composition of serum Cu shows potential as a new approach for the prognosis of liver disease, and although further investigation is required, for evaluation of the mortality risk in end-stage liver disease and prioritization of liver transplants.
Chronic kidney disease (CKD) is a general term for disorders that affect the structure and function of the kidneys. Iron deficiency (ID) and anemia occur in the vast majority of CKD patients, most of whom are elderly. However, establishing the cause of anemia in CKD, and therefore making an informed decision concerning the corresponding therapeutic treatment, is still a challenge. High-precision Fe isotopic analysis of blood serum samples of CKD patients with and without ID/anemia was performed via multi-collector inductively coupled plasma-mass spectrometry (MC-ICP-MS) for such a purpose. Patients with CKD and/or iron disorders showed a heavier serum Fe isotopic composition than controls. Many clinical parameters used for the diagnosis and follow-up of anemia correlated significantly with the serum Fe isotopic composition. In contrast, no relation was observed between the serum Fe isotopic composition and the estimated glomerular filtration rate as a measure of kidney function. Among the CKD patients, the serum Fe isotopic composition was substantially heavier in the occurrence of ID anemia, while erythropoietin-related anemia did not exert this effect. The Fe isotopic composition can thus be useful for distinguishing these different types of anemias in CKD patients, i.e. ID anemia vs. erythropoietin-related anemia.
3433wileyonlinelibrary.com (RAFT) is particularly well suited to synthesize sulfur-end-functionalized polymers due to the use of thiocarbonate RAFT chain transfer agents (CTAs). [ 4 ] It is known that size, shape, and surface chemistry of goldNP affect their uptake by living cells. [ 5 ] However, few have been reported on whether altering the hydrophilic-to-hydrophobic ratio of a polymer coating can affect cellular interaction. In this paper we report on goldNP decorated with a series of polymers that differ in their hydrophilic-to-hydrophobic comonomer ratio and investigate how the latter affects cellular uptake. In addition, we developed a novel fl ow cytometry method for label-free investigation of goldNP-cell interaction. This methodology is then used to investigate the different parameters that affect the interaction of the goldNP and in vitro cultured cells.It is demonstrated how cellular uptake and protein corona of (co)polymercoated gold nanoparticles can be altered by the hydrophilic-to-hydrophobic comonomer ratio. A novel, label-free fl ow cytometry strategy is developed to investigate particle uptake. These fi ndings offer insight in the design and analysis of hybrid nanomaterials for interfacing with biological systems.
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