Approaches and challenges in the diagnosis and management of secondary progressive multiple sclerosis: A Central Eastern European perspective from healthcare professionals.

Secondary progressive multiple sclerosis (SPMS) is a debilitating condition characterized by gradual worsening after an initial relapsing disease course. Despite the recent advances in our understanding of the disease, the diagnosis and treatment of SPMS continue to be challenging in routine clinical practice. The aim of this review article is to present the views of leading MS experts on the challenges in the diagnosis and management of SPMS and clinicians' perspectives in Central and Eastern Europe.

Zebrafish notch signalling pathway mutants exhibit trunk vessel patterning anomalies that are secondary to somite misregulation.

The Notch signalling pathway mutants, after-eight (aei), beamter (bea), and deadly-seven (des) have previously been used to study somitogenesis and neurogenesis. Notch signalling has also been shown to have roles in vascular development. However, vascular development in each of these three Notch mutants has not been described, and so their potential usefulness for further understanding the role of Notch signalling in angiogenesis is unknown.

Thalidomide induces limb defects by preventing angiogenic outgrowth during early limb formation.

Thalidomide is a potent teratogen that induces a range of birth defects, most commonly of the developing limbs. The mechanisms underpinning the teratogenic effects of thalidomide are unclear. Here we demonstrate that loss of immature blood vessels is the primary cause of thalidomide-induced teratogenesis and provide an explanation for its action at the cell biological level.

Functional consequences of cysteine modification in the ligand binding sites of peroxisome proliferator activated receptors by GW9662.

In the course of a high throughput screen to search for ligands of peroxisome proliferator activated receptor-gamma (PPARgamma), we identified GW9662 using a competition binding assay against the human ligand binding domain. GW9662 had nanomolar IC(50) versus PPARgamma and was 10- and 600-fold less potent in binding experiments using PPARalpha and PPARdelta, respectively. Pretreatment of all three PPARs with GW9662 resulted in the irreversible loss of ligand binding as assessed by scintillation proximity assay.