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Low serum albumin concentrations are associated with disease severity in patients with myasthenia gravis.
Weng, YY, Yang, DH, Qian, MZ, Wei, MM, Yin, F, Li, J, Li, X, Chen, Y, Ding, ZN, He, YB, et al
Medicine. 2016;(39):e5000
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Abstract
Serum albumin (S-Alb) is a widely used biomarker of nutritional status and disease severity in patients with autoimmune diseases. We investigated the correlation between S-Alb and the severity of myasthenia gravis (MG).A total number of 166 subjects were recruited in the study. Subjects were divided into 3 groups (T1 to T3) by S-Alb levels: T1: 21.1 to 38.4 g/L, T2: 38.5 to 41.5 g/L, T3: 41.6 to 48.9 g/L. Regression analysis was performed to determine the correlation of initial albumin concentrations and the severity of disease of MG.Lower levels of S-Alb were observed in subjects with increased disease severity than those with slight disease severity, meanwhile, incidence of myasthenia crisis increased in the lower albumin tertiles (P < 0.001). The disease severity assessment was performed according to the criteria established by the Myasthenia Gravis Foundation of America. After adjusting for age, sex, body mass index (BMI), and duration of disease, it showed that higher S-Alb concentrations were associated with lower disease severity. Odds ratios (ORs) of T2 to T3 were 0.241 (95% CI: 0.103-0.566, P < 0.001), 0.140 (95% CI: 0.054-0.367, P < 0.001) when compared with subjects in the T1, respectively. When subjects were stratified into hypoalbuminemia and normal albumin groups, we found that the association between S-Alb and MG remained significant in the hypoalbuminemia group only (OR: 0.693, 95% CI: 0.550-0.874, P = 0.002) after further adjustment for age, sex, BMI, and duration of disease.This is the first study to demonstrate that S-Alb was independently associated with MG severity. In patients with low S-Alb, S-Alb concentration could be a potential biomarker for MG disability.
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Sulfation of Lower Chlorinated Polychlorinated Biphenyls Increases Their Affinity for the Major Drug-Binding Sites of Human Serum Albumin.
Rodriguez, EA, Li, X, Lehmler, HJ, Robertson, LW, Duffel, MW
Environmental science & technology. 2016;(10):5320-7
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Abstract
The disposition of toxicants is often affected by their binding to serum proteins, of which the most abundant in humans is serum albumin (HSA). There is increasing interest in the toxicities of environmentally persistent polychlorinated biphenyls (PCBs) with lower numbers of chlorine atoms (LC-PCBs) due to their presence in both indoor and outdoor air. PCB sulfates derived from metabolic hydroxylation and sulfation of LC-PCBs have been implicated in endocrine disruption due to high affinity-binding to the thyroxine-carrying protein, transthyretin. Interactions of these sulfated metabolites of LC-PCBs with HSA, however, have not been previously explored. We have now determined the relative HSA-binding affinities for a group of LC-PCBs and their hydroxylated and sulfated derivatives by selective displacement of the fluorescent probes 5-dimethylamino-1-naphthalenesulfonamide and dansyl-l-proline from the two major drug-binding sites on HSA (previously designated as Site I and Site II). Values for half-maximal displacement of the probes indicated that the relative binding affinities were generally PCB sulfate ≥ OH-PCB > PCB, although this affinity was site- and congener-selective. Moreover, specificity for Site II increased as the numbers of chlorine atoms increased. Thus, hydroxylation and sulfation of LC-PCBs result in selective interactions with HSA which may affect their overall retention and toxicity.