Multiattribute Monitoring of Antibody Charge Variants by Cation-Exchange Chromatography Coupled to Native Mass Spectrometry.

The aim of this study was to characterize the product variants of a therapeutic T-cell bispecific humanized monoclonal antibody (TCB Mab, ∼200 kDa, asymmetric) and to develop an online cation-exchange chromatography native electrospray mass spectrometry method (CEC-UV-MS) for direct TCB Mab charge variant monitoring during bioprocess and formulation development. For the identification and functional evaluation of the diverse and complex TCB Mab charge variants, offline fractionation combined with comprehensive analytical testing was applied. The offline fractionation of abundant product variant peaks enabled identification of coeluting acid charge variants such as asparagine deamidation, primary and secondary Fab glycosylation (with and without sialic acid), and the presence of O-glycosylation in the G4S-linker region.

Extrarenal Na+ balance, volume, and blood pressure homeostasis in intact and ovariectomized deoxycorticosterone-acetate salt rats.

Water-free Na+ storage may buffer extracellular volume and mean arterial pressure (MAP) in spite of Na+ retention. We studied the relationship among internal Na+, K+, water balance, and MAP in Sprague-Dawley rats, with or without deoxycorticosterone-acetate (DOCA) salt, with or without ovariectomy (OVX). The rats were fed a low-salt (0.

Internal sodium balance in DOCA-salt rats: a body composition study.

The idea that Na(+) retention inevitably leads to water retention is compelling; however, were Na(+) accumulation in part osmotically inactive, regulatory alternatives would be available. We speculated that in DOCA-salt rats Na(+) accumulation is excessive relative to water. Forty female Sprague-Dawley rats were divided into four subgroups.

Osmotically inactive skin Na+ storage in rats.

Compared with age-matched men, women are resistant to the hypertensive effects of dietary NaCl; however, after menopause, the incidence of salt-sensitive hypertension is similar in women and men. We recently suggested that osmotically inactive Na+ storage contributes to the development of salt-sensitive hypertension. The connective tissues, including those immediately below the skin that may serve as a reservoir for osmotically inactive Na+ storage, are affected by menopause.

Reduced osmotically inactive Na storage capacity and hypertension in the Dahl model.

Recent evidence suggested that Na can be stored in an osmotically inactive form. We investigated whether osmotically inactive Na storage is reduced in a rat model of salt-sensitive (SS) hypertension. SS and salt-resistant (SR) Dahl-Rapp rats as well as Sprague-Dawley (SD) rats were fed a high (8%)- or low (0.