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Background/Aims: Possible predictive value of aortic-brachial arterial stiffness mismatch assessed by pulse wave velocity PWV ratio in peritoneal dialysis patients' outcomes need to be further elucidated. The aim of this study is to investigate the predictor value of PWV ratio on peritoneal dialysis (PD) patients' outcomes in China. Methods: In this longitudinal cohort study, patients who started PD during September 20, 2005, to February 05, 2008, were included. All the patients were followed until January 31, 2018. Aortic-brachial arterial stiffness mismatch was assessed using carotid-femoral pulse wave velocity divided by carotid-radial pulse wave velocity (PWV ratio). Results: A total of 181 incident PD patients were included. The median survival of patients in PWV ratio above median group (4.03 years, 95% CI 4.64-7.99 years) was shorter than that of PWV ratio below median group (10.43 years, 95% CI 9.74-11.12 years, p< 0.001). The cardiovascular mortality rate in PWV ratio above median group were significantly higher than that of PWV below median group (log rank test, p< 0.001). Univariate Cox regression analysis showed that both PWV ratio (HR 2.42, 95% CI 1.80-3.25, p< 0.001) and CF-PWV (HR 1.27, 95% CI 1.16-1.38, p< 0.001) were associated with high patients' all-cause mortality. Multivariable Cox regression analysis showed that the PWV ratio was a strong and significantly predictor of cardiovascular mortality (HR 2.08 95% CI 1.16-3.71, p=0.014) after adjusting for coronary heart disease history (HR 2.39, 95% CI 1.20-4.76, p=0.013), diabetes mellitus history (HR 2.84, 95% CI 1.51-5.33, p=0.001). However, the CF-PWV was failed to be included as a significant predictor for both all-cause and CVD mortality in the multivariable Cox regression model. Conclusion: Aortic-brachial arterial stiffness mismatch as assessed by PWV ratio, a new arteries stiffness risk parameter, is a significant prognostic indicator of CVD mortality in PD patients. We demonstrated that the discriminative power of the PWV ratio for both all-cause and CVD mortality was better than that CF-PWV. [ABSTRACT FROM AUTHOR]

Purposes: The main purposes of this article are to describe an unprecedented phenomenon in which significant amount of a shoulder peak impurity was observed during normal non-reducing capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) analysis of a recombinant fusion protein X, and to evaluate the root cause for this phenomenon. Methods: A series of experiments were conducted to study the nature of this degradation. Effects of iodoacetamide (IAM), heating temperature, duration, and SDS on the formation of this specific impurity were evaluated using a variety of characterization techniques. Results: The formation of the impurity as observed in CE-SDS was actually due to alkylation of lysine and serine residues with IAM, as confirmed by peptide mapping and LC-MS/MS, which increased the molecular weight and therefore decreased the electrophoretic mobility. The amount of impurity was also strongly dependent on sample preparation conditions including the presence or absence of SDS. Conclusions: Our study clearly suggested that even though IAM has been used extensively as an alkylation reagent in the traditional non-reducing CE-SDS analysis of monoclonal antibodies and other proteins, alkylation with IAM could potentially lead to additional impurity peak, and therefore complicating analysis. Therefore, before performing CE-SDS and other analyses, the effects of sample preparation procedures on analytical results must be evaluated. For protein X, IAM should be excluded for CE-SDS analysis. [ABSTRACT FROM AUTHOR]

We have observed an interesting phenomenon in which grinding of freeze-dried monoclonal antibody X (mAb-X) formulation powder resulted to significant protein sub-visible particles (SbVPs) in the reconstituted liquid, which could only be observed by sensitive particle analytical methods such as MFI and DLS. Effects of grinding temperature and the free radical scavengers methionine and 3-carbamoyl-2,2,5,5-tetramethyl-1-pyrrolidin-yloxy free radical (CTPO) on the formation of SbVPs were also evaluated. Free radicals were observed by EPR and the amount of free radicals was correlated to the sample temperature prior to grinding. Formation of SbVPs could be partially inhibited by methionine and CTPO. The amount of SbVPs formed was dependent on the amount of free radicals/sample temperature prior to grinding. At higher temperatures, more free radicals and SbVPs formed. Other than the previously known protein degradation due to high temperature formed during mechanical grinding, we propose an unreported and supplementary mechanism, i.e., the formation of free radicals (i.e., due to break of C O or C S bonds) in the dried state during mechanical grinding, leading to protein particle formation in the reconstituted solution. Our observation suggested that mechanical grinding of protein powder should be avoided or used cautiously (i.e., grinding temperature, strength and time) and the effects on radical and particle formation be fully evaluated. [ABSTRACT FROM AUTHOR]