Octanorm [cutaquig®], a new immunoglobulin (human) subcutaneous 16.5% solution for injection (165 mg/mL) - Biochemical characterization, pathogen safety, and stability.

Octanorm (marketed as cutaquig® in Canada and US [2018] and registered in several European countries [2019]) is a new immunoglobulin subcutaneous 16.5% liquid for the treatment of patients with primary immune deficiency (PID) and secondary immune deficiency (SID) depending on country's specific indications. Octanorm contains ≥96% human IgG and is characterized by especially low concentrations of polymers and aggregates, IgA and IgM, a physiological osmolality along with a low isoagglutinin titer. The Octanorm manufacturing process is based on the well-established IVIG octagam® 5% and 10% process, but yields a higher immunoglobulin concentration of 16.5% in the final product. Octanorm shows a distribution of immunoglobulin G subclasses closely proportional to native human plasma and comprises a broad spectrum of antibodies against infectious agents. Potential procoagulant activity is not detectable. IgG functionality and physico-chemical integrity have been demonstrated by state-of-the-art-methods. The virus safety of Octanorm is ensured via a combination of three validated independent methods as part of the manufacturing process. Substantial prion depletion during the manufacturing process has also been demonstrated. Compared with other commercially available subcutaneous immunoglobulin (SCIG) 20% products, Octanorm 16.5% shows a lower viscosity, which is a valuable feature that allows for a more comfortable infusion experience.

Estrogen-like effects of wine extracts on nitric oxide synthesis in human endothelial cells.

Endothelial dysfunction frequently ensues during the climacteric due to hormonal and metabolic changes. Non-pharmacological interventions such as lifestyle and dietary modifications are emerging as valuable strategies to counteract the cardiovascular consequences of ageing. A number of chemical components of wine, including alcohol and some polyphenols, are known to be active on the vessels. However, the molecular mechanisms through which they modulate endothelial function are largely unclear. The aim of this study was to investigate the effects of non-alcoholic wine fractions from five different wines on the synthesis of nitric oxide (NO) via the expression and enzymatic activation of the endothelial nitric oxide synthase (eNOS) in human endothelial cells. All non-alcoholic fractions studied increased NO synthesis, although with different potencies. All wine extracts maximally enhanced NO production at doses in the range achieved with a moderate wine intake, with decreasing effects with further increases of the dose. Interestingly, a part of these actions was recruited via estrogen receptors (ERs). Within the polyphenols with known binding activity for ERs contained in the tested wines, resveratrol, epicatechin, syringic acid, apigenin, malvidin and ellagic acid were largely responsible for eNOS activation. These findings show that some of the non-alcoholic components of wine enhance the production of NO by the vessels acting on ERs, and suggest that a moderate intake of wine may benefit the cardiovascular system through estrogen-like effects.

Mass transfer characteristics of plasmids in monoliths.

The hydrodynamic properties and pore-structure of monoliths based on functionalized poly(glycidyl methacrylate-ethylene dimethacrylate) were characterised by pulse response experiments using different probes representing a wide range of molecular mass. On a small scale, band spreading was found to be caused to the extent of more than 90% by extra-column effects. These monoliths have large channel diameters, providing a suitable chromatography adsorbent for processing of large molecules. Dynamic and static binding capacity for plasmid DNA was investigated. For our model plasmid, consisting of 4.9 kbp, a capacity of 7 mg/mL was observed in comparison to 0.3 mg/mL for a conventional medium designed for protein separation. When plasmids were loaded on the monolith a gradual increase in pressure drop was observed. The channels filled up and the cross-sectional area available for liquid flow decreased. Therefore, a higher pressure drop was observed during elution. This is caused by (i) shrinking of the channels as effect of the high salt concentration, (ii) high viscosity of the mobile phase due to high concentration of plasmids, and (iii) an increase of the hydrodynamic radius of the plasmid with salt concentration from 45 nm at 150 mM to 70 nm at 2 M NaCl, as measured by dynamic light scattering. These types of monoliths are considered to be the preferred adsorbents for plasmid separation.