Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.16 (calcineurin)
 17,112 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Inquiries into the neurochemical mechanisms of vestibular compensation, a model of lesion-induced neuronal plasticity, reveal the involvement of both voltage-gated Ca(2+) channels (VGCC) and intracellular Ca(2+) signaling. Indeed, our previous microarray analysis showed an up-regulation of some calcium signaling-related genes such as the alpha2 subunit of L-type calcium channels, calcineurin, and plasma membrane Ca(2+) ATPase 1 (PMCA1) in the ipsilateral vestibular nuclear complex (VNC) following unilateral vestibular deafferentation (UVD). To further elucidate the role of calcium signaling-related molecules in vestibular compensation, we used a quantitative real-time polymerase chain reaction (PCR) method to confirm the microarray results and investigated changes in expression of these molecules at various stages of compensation (6 h to 2 weeks after UVD). We also investigated the changes in gene expression during Bechterew's phenomenon and the effects of a calcineurin inhibitor on vestibular compensation. Real-time PCR showed that genes for the alpha2 subunit of VGCC, PMCA2, and calcineurin were transiently up-regulated 6 h after UVD in ipsilateral VNC. A subsequent UVD, which induced Bechterew's phenomenon, reproduced a complete mirror image of the changes in gene expressions of PMCA2 and calcineurin seen in the initial UVD, while the alpha2 subunit of VGCC gene had a trend to increase in VNC ipsilateral to the second lesion. Pre-treatment by FK506, a calcineurin inhibitor, decelerated the vestibular compensation in a dose-dependent manner. Although it is still uncertain whether these changes in gene expression are causally related to the molecular mechanisms of vestibular compensation, this observation suggests that after increasing the Ca(2+) influx into the ipsilateral VNC neurons via up-regulated VGCC, calcineurin may be involved in their synaptic plasticity. Conversely, an up-regulation of PMCA2, a brain-specific Ca(2+) pump, would increase an efflux of Ca(2+) from those neurons and perhaps prevent cell damage following UVD.
 ...
PMID:Unilateral vestibular deafferentation-induced changes in calcium signaling-related molecules in the rat vestibular nuclear complex. 1727 94

Treatment of pyoderma gangrenosum (PG) remains a challenge, and there are currently no specific or uniformly effective therapies. Although widespread or rapidly progressive disease often requires systemic treatment, localised and mild lesions may be effectively controlled with topical agents. The most frequently applied topical drugs are corticosteroids and calcineurin inhibitors. Recently, a patient with idiopathic PG of the lower limb was successfully treated with topical timolol and collagenase. Here, we report a case of a patient with collagenous colitis, ankylosing spondylitis and periumbilical PG. Persistent ulcerated skin lesions were successfully treated with topical timolol, although a flare of the underlying bowel disease temporarily interrupted the improvement. The case presented enhances the previously reported therapeutic potential of topical timolol in the treatment of PG. Control of chronic underlying disorders is critical to prevent rebound flares and maintain the benefit.
 ...
PMID:Topical timolol for the treatment of pyoderma gangrenosum. 2813 Feb 88