Site-specific PEGylation of micro-plasmin for improved thrombolytic therapy through engineering enhanced resistance against serpin mediated inhibition.

The relatively rapid inhibition of microplasmin by α2-AP leads to short functional half-life of the molecule in vivo, causing inefficient clot dissolution, even after site-specific, local catheter-based delivery. Here, we describe a PEGylation approach for improving the therapeutic potential via improving the survival of microplasmin in presence of its cognate inhibitor, α2-AP, wherein a series of strategically designed cysteine analogs of micro-plasminogen were prepared and expressed in E. coli, and further modified by covalent grafting in vitro with PEG groups of different molecular sizes so as to select single or double PEG chains that increase the molecular weight and hydrodynamic radii of the conjugates, but with a minimal discernible effect on intrinsic plasmin activity and structural framework, as explored by amidolytic activity and CD-spectroscopy, respectively.

Biomarkers of Cardiac Health and Disease.

Cardiovascular diseases (CVDs) are globally associated with high rates of morbidity and mortality. CVDs are diagnosed based on clinical assessment, physical examination, disease history, electrocardiogram, and chest X-ray. However, these parameters have limited sensitivity and specificity.

Optical Coherence Tomography and Subclinical Optical Neuritis in Longitudinally Extensive Transverse Myelitis.

Objective: The aim is to compare the retinal nerve fiber layer (RNFL) thickness of longitudinally extensive transverse myelitis (LETM) eyes without previous optic neuritis with that of healthy control subjects.

Methods: Over 20 LETM eyes and 20 normal control eyes were included in the study and subjected to optical coherence tomography to evaluate and compare the RNFL thickness.

Result: Significant RNFL thinning was observed at 8 o'clock position in LETM eyes as compared to the control eyes ( = 0.