We found that even before dialysis, oxidative stress was enhanced in correlation with the level of renal dysfunction among patients with chronic renal failure. In the future, antioxidant strategies should become part of treatment for predialysis renal failure.

Ebola virus (EBOV) is the causative agent of severe hemorrhagic fever in primates, with human case fatality rates up to 90%. Today, there is neither a licensed vaccine nor a treatment available for Ebola hemorrhagic fever (EHF). Single monoclonal antibodies (MAbs) specific for Zaire ebolavirus (ZEBOV) have been successfully used in passive immunization experiments in rodent models, but have failed to protect nonhuman primates from lethal disease. In this study, we used two clones of human-mouse chimeric MAbs (ch133 and ch226) with strong neutralizing activity against ZEBOV and evaluated their protective potential in a rhesus macaque model of EHF. Reduced viral loads and partial protection were observed in animals given MAbs ch133 and ch226 combined intravenously at 24 hours before and 24 and 72 hours after challenge. MAbs circulated in the blood of a surviving animal until virus-induced IgG responses were detected. In contrast, serum MAb concentrations decreased to undetectable levels at terminal stages of disease in animals that succumbed to infection, indicating substantial consumption of these antibodies due to virus replication. Accordingly, the rapid decrease of serum MAbs was clearly associated with increased viremia in non-survivors. Our results indicate that EBOV neutralizing antibodies, particularly in combination with other therapeutic strategies, might be beneficial in reducing viral loads and prolonging disease progression during EHF.

Background Oxidative stress is enhanced in advanced chronic kidney disease (CKD) patients and recognized as a main contributor to cardiovascular disease. Carbonyl stress is also known to be enhanced in advanced CKD; however the precise relationship between oxidative stress and carbonyl stress is not clear. The aim of this study was to investigate potential relationships between oxidative stress, carbonyl stress, and renal function among predialysis patients with CKD. Methods A total of 32 predialysis CKD patients (22 male, 10 female) were divided into four groups according to their values for creatinine clearance (Ccr) (group A, C60 ml/min; group B, 45-59 ml/min; group C, 30-44 ml/min; group D, B29 ml/min). As main markers of oxidative and carbonyl stresses, the redox state of Cys-34 (free thiol group) of human serum albumin [HSA(Cys-34)-redox] and the carbonyl content of serum proteins were employed, respectively.Results The values for the fraction of both reversibly oxidized HSA [f(HNA-1)] and irreversibly oxidized HSA [f(HNA-2)] significantly increased with a decrease in renal function (group A, 21.0 ± 3.4 and 1.8 ± 0.3%; group D, 31.1 ± 4.1 and 2.7 ± 0.9%, respectively). The value for carbonyl content also significantly increased with a decrease in renal function (group A, 0.7 ± 0.1 nmol/mg protein; group D, 1.1 ± 0.2 nmol/mg protein). There was a significant positive correlation between carbonyl content and the f(HNA-2) value, while such a correlation was not observed between carbonyl content and the f(HNA-1) value, suggesting that there is a close relationship between serum protein carbonylation and irreversible albumin thiol oxidation. Conclusions There is a close relationship between oxidative stress and carbonyl stress and these are enhanced in correlation with the level of renal dysfunction among predialysis CKD patients.

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Background: Oxidative stress (OS) is reportedly enhanced in patients receiving regular hemodialysis (HD). However, the in vivo redox state of HD patients, particularly after HD sessions, remains unclear. This study aimed to clarify the influence of HD on OS using the albumin redox state as a marker. Method: Blood samples of 8 regular HD patients were obtained during the course of study. The redox state of albumin was determined using high-performance liquid chromatography. Results: The mean fraction of reversibly oxidized albumin [f(HNA-1)] declined significantly over the course of the session and reached a minimum 4 h after the session had ended (pre-HD, 36.16 ± 7.50%; 4 h after HD, 25.71 ± 6.41%), then gradually rose to predialytic levels. The proportion of irreversibly oxidized albumin did not change significantly over time. Positive correlations were demonstrated between f(HNA-1) and uremic small solutes in each case. Conclusion: Accumulation of dialyzable uremic solutes may contribute to OS in HD patients.