Patients with temporomandibular disorders have increased fatigability of the cervical extensor muscles

To determine whether patients with myogenous and mixed temporomandibular disorders (TMD) have greater fatigability of the cervical extensor muscles while performing a neck extensor muscle endurance test (NEMET) when compared with healthy controls.

Closure of apical access site after transapical, transcatheter paravalvular leak closure

The safety of percutaneous transapical mitral paravalvular leak (PVL) closure could potentially be enhanced by device closure of the ventricular access site. Percutaneous transapical PVL closure was performed. The 9F delivery sheath was pulled back, and a 6-mm Amplatzer muscular ventricular septal defect occluder was deployed at the apical puncture site. Immediate hemostasis was achieved. Total hospitalization was 9 days. New York Heart Association functional class was improved, hemoglobin and haptoglobin rose, while lactate dehydrogenase fell. Follow-up fluoroscopy and transthoracic echocardiography revealed a good functional result. Closure of the apical access site by means of an Amplatzer muscular ventricular septal defect occluder is feasible.

Lead discovery, chemistry optimization, and biological evaluation studies of novel biamide derivatives as CB2 receptor inverse agonists and osteoclast inhibitors

N,N'-((4-(Dimethylamino)phenyl)methylene)bis(2-phenylacetamide) was discovered by using 3D pharmacophore database searches and was biologically confirmed as a new class of CB(2) inverse agonists. Subsequently, 52 derivatives were designed and synthesized through lead chemistry optimization by modifying the rings A-C and the core structure in further SAR studies. Five compounds were developed and also confirmed as CB(2) inverse agonists with the highest CB(2) binding affinity (CB(2)K(i) of 22-85 nM, EC(50) of 4-28 nM) and best selectivity (CB(1)/CB(2) of 235- to 909-fold). Furthermore, osteoclastogenesis bioassay indicated that PAM compounds showed great inhibition of osteoclast formation. Especially, compound 26 showed 72% inhibition activity even at the low concentration of 0.1 μM. The cytotoxicity assay suggested that the inhibition of PAM compounds on osteoclastogenesis did not result from its cytotoxicity. Therefore, these PAM derivatives could be used as potential leads for the development of a new type of antiosteoporosis agent.

Modulation of signal transduction by vitamin E

The ability of vitamin E to modulate signal transduction and gene expression has been observed in numerous studies; however, the detailed molecular mechanisms involved are often not clear. The eight natural vitamin E analogues and synthetic derivatives affect signal transduction with different potency, possibly reflecting their different ability to interact with specific proteins. Vitamin E modulates the activity of several enzymes involved in signal transduction, such as protein kinase C, protein kinase B, protein tyrosine kinases, 5-, 12-, and 15-lipoxygenases, cyclooxygenase-2, phospholipase A2, protein phosphatase 2A, protein tyrosine phosphatase, and diacylglycerol kinase. Activation of some these enzymes after stimulation of cell surface receptors with growth factors or cytokines can be normalized by vitamin E. At the molecular level, the translocation of several of these enzymes to the plasma membrane is affected by vitamin E, suggesting that the modulation of protein-membrane interactions may be a common theme for vitamin E action. In this review the main effects of vitamin E on enzymes involved in signal transduction are summarized and the possible mechanisms leading to enzyme modulation evaluated. The elucidation of the molecular and cellular events affected by vitamin E could reveal novel strategies and molecular targets for developing similarly acting compounds.