“
“Although high serum levels of galactose-deficient

IgA1 (an important biomarker of IgA nephropathy (IgAN)) are found in most patients with IgAN, their relationship to disease learn more severity and progression remains unclear. To help clarify this we prospectively enrolled 275 patients with IgAN and followed them for a median of 47 months (range 12-96 months). Serum galactose-deficient IgA1 was measured at the time of diagnosis using a lectin-based ELISA, and renal survival was modeled using the Cox proportional hazards method. The serum levels of galactose-deficient IgA1 were higher in patients with IgAN compared to those in healthy controls. Importantly, in adjusted analysis, higher levels of galactose-deficient IgA1 were independently associated with a greater risk of deterioration in renal function with a hazard ratio of 1.44 per standard deviation of the natural log-transformed galactose-deficient IgA1 concentration. In reference to the first quartile, the risk

of kidney failure increased such that the hazard ratio for the second quartile was 2.47, 3.86 for the third, and 4.76 for the fourth quartile of the galactose-deficient IgA1 concentration. Hence, elevated serum levels of galactose-deficient IgA1 are associated with a poor prognosis in IgAN. Kidney International (2012) 82, 790-796; doi:10.1038/ki.2012.197; published online 6 June 2012″
“L-Arginine hydrochloride (L-ArgHCl) was found to be an effective enhancer for in vitro protein refolding more than two decades ago. Sotrastaurin mw A detailed understanding of the mechanism buy BI-D1870 of action, by which L-ArgHCl as co-solvent is capable to effectively suppress protein aggregation, while protein stability is preserved, has remained elusive. Concepts for the effects of co-solvents, which have been established over the last decades, were found to be insufficient to completely explain the effects of L-ArgHCl on protein refolding. In this article, we present data, which clearly establish that L-ArgHCl acts on the equilibrium solubility of the native model protein recombinant plasminogen

activator (rPA), while for S-carboxymethylated rPA (IAA-rPA) that served as a model protein for denatured protein states, equilibrium solubilities could not be obtained. Solid to solute free transfer energies for native rPA were lowered by up to 14 kJ mol(-1) under the tested conditions. This finding is in marked contrast to a previously proposed model in which L-ArgHCl acts as a neutral crowder which exclusively has an influence on the stability of the transition state of aggregation. The effects on the apparent solubility of IAA-rPA, as well as on the aggregation kinetics of all studied protein species, that were observed in the present work could tentatively be explained within the framework of a nucleation-aggregation scheme, in which L-ArgHCl exerts a strong effect on the pre-equilibria leading to formation of the aggregation seed.