With the aim of the production of human factor VIII antigen and its corresponding antibody an epitope coding fragment of the light-chain of hFVIII, fused to a His6-tag, was isolated and over-expressed in Escherichia coli. The over-expressed hFVIII-epitope containing peptide was confirmed by its reaction with a rabbit serum directed against native hFVIII as well as antiHis6-tag antibody. An expr...

objective(s):the neuropeptide calcitonin gene-related peptide (cgrp) has long been postulated to play an integral role in the pathophysiology of migraine. earlier studies showed that cgrp can stimulate the synthesis and release of nitric oxide (no) and cytokines from trigeminal ganglion glial cells. the purpose of this study was to determine the effect of 17β-estradiol in regulation of cgrp exp...

Introduction: Migraine is a highly devastating neurovascular disorder that affects up to 16% of the population worldwide. In spite of intensive research, its origin remains enigmatic with no therapeutic option appropriate for all migraine patients. One of the leading hypotheses is related to the function of the calcitonin gene-related peptide (CGRP). Regardless, the pharmaceutical options curre...

A highly efficient, asymmetric synthesis of telcagepant (1), a CGRP receptor antagonist for the treatment of migraine, is described. This synthesis features the first application of iminium organocatalysis on an industrial scale. The key to the success of this organocatalytic transformation was the identification of a dual acid cocatalyst system, which allowed striking a balance of the reaction...

of the Dissertation xi Chapter 1: Introduction 1 Chapter 2: PDF receptor preferentially couples to AC3 in small LNv cells in Drosophlia 22 Chapter 3: PDF receptor signalosome components vary between pacemaker subgroups 61 Chapter 4: Daily changes in PDF receptor signaling 83 Chapter 5: DH81 is a potent activator of the CGRP receptor encoded by CG4395 108

Osteoarthritis (OA) pain is poorly understood and managed, as current analgesics have only limited efficacy and unwanted side effect profiles. A broader understanding of the pathological mechanisms driving OA joint pain is vital for the development of improved analgesics. Both clinical and preclinical data suggest an association between joint levels of the sensory neuropeptide calcitonin gene-r...

To determine the role of endothelin-1 (ET-1) and its receptors in the regulation of calcitonin gene-related peptide (CGRP) release, male Wistar rats were divided into six groups and subjected to the following treatments for 1 wk with or without ABT-627 (an ET(A) receptor antagonist, 5 mg.kg(-1).day(-1) in drinking water) or A-192621 (an ET(B)-receptor antagonist, 30 mg.kg(-1).day(-1) by oral ga...

Recent findings CGRP is widely distributed in the nervous system, particularly at anatomical areas thought to be involved with migraine, including the trigeminovascular nociceptive system. In studies, CGRP has been shown to be released during severe migraine attacks, and effective triptan treatment of an attack normalizes these levels. CGRP administration triggers migraine in patients and CGRP ...