Function of the Golgi apparatus in protein maturation
The most important subcellular structure in the context of wrinkly skin syndrome (WSS), is the Golgi apparatus. The Golgi apparatus is an important part of the endomembrane system because it processes proteins and lipids prior to their delivery to the plasma membrane and/or secretion into the extracellular environment. The Golgi is organized into a polarized series of membrane-bound stacks, called cisternae, through which proteins are trafficked in sequence once they leave the endoplasmic reticulum (ER), where the proteins and lipids are synthesized. Proteins destined for secretion or delivery to the plasma membrane arrive first at the cis-Golgi, before being trafficked through the medial and trans-Golgi. In the Golgi, proteins undergo extensive post-translational modifications (PTMs). In the context of WSS, the most significant PTM events are the glycosylation of proteins comprising the extracellular matrix (ECM) of epidermal cells. The two types of glycosylation events in the Golgi are N-linked glycosylation and O-linked glycosylation. Glycosylation of proteins destined for secretion occurs through the forward movement of proteins throughout the Golgi apparatus. The proteins destined for secretion are then trafficked to the plasma membrane in secretory vesicles. Retrograde (backward) transport in the Golgi apparatus is also important. In order to retain the enzymes responsible for protein glycosylation in the correct regions of the Golgi, there must be retrograde transport of these enzymes back into the Golgi apparatus.
A patent to use digoxin immunoglobulins C07k16/44 as a regulator of the preeclamptic/eclamptic patients sodium/potassium ATPase activity was approved in 2003 to Charles David Adair under application number WO2004011028A1. Commercial aspects
Price increase was reported to range from US $380 to US $750 during 2013 for digoxin-Fab. However, these price increases are not reflective of the United States average AWP for digoxin-Fab as it represents Australian costs converted to US. Prior to 2011, Digibind and DigiFab pricing was US $797 per 38 mg vial and US $786 per 40 mg vial respectively. After GSK discontinued Digibind sale in USA in 2011, the AWP of DigiFab increases by 15% to US $903 per 40 mg vial. AWP of DigiFab has continued to increase as much as 54% occurring in March 2014 to US $2,370 per 40 mg vial. However, the cost may vary depending on wholesaler contractor manufacturer rebates. References
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Drug information online
Digibind description